Molecular Design of Naphthalene- and Carbazole-Based Monomers for Regiospecific Synthesis of Poly(arylenevinylene)s via Co-Catalyzed Hydroarylation Polyaddition.

This study focuses on the development of regiospecific hydroarylation polyaddition of naphthalene- and carbazole-based monomers with diynes under mild reaction conditions at room temperature. A 1-pyrazole substituent serves as an appropriate directing group for a Co-catalyst to efficiently activate the C-H bonds of generally inactive six-membered aromatic hydrocarbons. The 1-pyrazole groups in 2,6-di(1-pyrazolyl)naphthalene adopt planar conformations and act as directing groups, resulting in a smooth hydroarylation reaction. In contrast, the reaction with 1,5-di(1-pyrazolyl)naphthalene do not proceed. The polyaddition reaction of 2,6-di(1-pyrazolyl)naphthalene selectively proceeds at 3,7-positions under mild reaction conditions at 30 °C, and yields corresponding poly(arylenevinylene) (PAV) with high molecular weight. This molecular design is also applicable to the hydroarylation polyaddition of carbazole; the polyaddition reaction of 9-(2-ethylhexyl)-3,6-di(1-pyrazolyl)carbazole selectively occurred at 2,7-positions. The optical and electronic properties of the synthesized compounds are evaluated. The obtained PAVs serve as an emitting material in organic light-emitting diode (OLED). This study aims to develop a Co-catalyzed hydroarylation polyaddition via C-H activation of generally inactive polyaromatic hydrocarbons (PAHs) under mild conditions.

Short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery for superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIMS: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. PATIENTS AND METHODS: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. RESULTS: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. CONCLUSION: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further.

D-alanine inhibits murine intestinal inflammation by suppressing IL-12 and IL-23 production in macrophages.

BACKGROUND AND AIMS: Free D-amino acids, which have different functions from L-amino acids, have recently been discovered in various tissues. However, studies on the potential interactions between intestinal inflammation and D-amino acids are limited. We examined the inhibitory effects of D-alanine on the pathogenesis of intestinal inflammation. METHODS: We investigated serum D-amino acid levels in 40 patients with ulcerative colitis and 34 healthy volunteers. For 7 d, acute colitis was induced using dextran sulfate sodium in C57BL/6J mice. Plasma D-amino acid levels were quantified in mice with dextran sulfate sodium-induced colitis, and these animals were administered D-alanine via intraperitoneal injection. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression in the colonic mucosa was measured using real-time PCR. In vitro proliferation assays were performed to assess naïve CD4+ T cell activation under Th-skewing conditions. Bone marrow cells were stimulated with mouse macrophage-colony stimulating factor to generate mouse bone marrow-derived macrophages. RESULTS: Serum D-alanine levels were significantly lower in patients with ulcerative colitis than in healthy volunteers. Dextran sulfate sodium-treated mice had significantly lower plasma D-alanine levels than control mice. D-alanine-treated mice had significantly lower disease activity index than control mice. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression levels were significantly lower in D-alanine-administered mice than in control mice. D-alanine suppressed naïve T cell differentiation into Th1 cells in vitro and inhibited the production of IL-12p35 and IL-23p19 in bone marrow-derived macrophages. CONCLUSIONS: Our results suggest that D-alanine prevents dextran sulfate sodium-induced colitis in mice and suppresses IL-12p35 and IL-23p19 production in macrophages.

Conventional versus underwater endoscopic resection for superficial non-ampullary duodenal epithelial tumours.

BACKGROUND AND OBJECTIVE: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion. METHODS: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching. RESULTS: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate. CONCLUSIONS: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.

Underwater clip closure method for mucosal defects after duodenal endoscopic submucosal dissection (with video).

Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection.

Characteristics of Gastric Mucosa-Associated Microbiota in Patients with Early Gastric Cancer After Successful Helicobacter pylori Eradication.

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.

Clinical Outcomes of Follow-Up Observation After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma Invading the Muscularis Mucosa Without Lymphovascular Involvement.

BACKGROUND: The therapeutic approach after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) diagnosed as pathological T1a-muscularis mucosa (pT1a-MM) without lymphovascular involvement (LVI) remains uncertain. We aimed to determine whether observation after ESD is acceptable for patients without LVI showing pT1a-MM cancer. METHODS: We retrospectively registered 566 ESCC patients who were treated with ESD at ten institutions between January 2007 and December 2015. Of those, 447 cases showing pT1a-epithelium/lamina propria mucosa (EP/LPM) without LVI and vertical margin (VM) (EP/LPM group), and 41 cases showing pT1a-MM without LVI and VM (MM group) were analyzed in this investigation. The clinical outcomes were assessed between the groups. RESULTS: The 5 year cumulative incidence of metastatic recurrence was 0.5% and 3.3% in the EP/LPM and MM groups, respectively (P = 0.121). Two cases showing pT1a-EP/LPM and one showing pT1a-MM experienced lymph node recurrence. The 5 year cumulative incidence of local recurrence was 1.5% and 3.8% in the EP/LPM and MM groups, respectively (P = 0.455). The 5 year disease-specific survival (DSS) rate was 99.3% and 96.6% in the EP/LPM and MM groups, respectively (P = 0.118), whereas the 5 year overall survival rate was significantly higher in the EP/LPM group than in the MM group (92.6% versus 81.1%, respectively; P = 0.021). CONCLUSIONS: As regards metastatic recurrence and DSS, ESCC patients with pT1a-MM without LVI showed favorable outcomes that were equivalent to those with pT1a-EP/LPM, even when they were not treated with additional therapy after ESD.

Partially hydrolyzed guar gum increased colonic mucus layer in mice via succinate-mediated MUC2 production.

Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.

Facile Synthesis of Bis-pentafluoroarylated Anthracene Derivatives for N-type Organic-Field-Effect Transistor Applications.

Diphenylanthracene (DPA) and its derivatives are promising semiconducting materials for p-type organic-field-effect transistors (OFETs). In this study, to develop n-type semiconducting materials with an anthracene core, pentafluorobenzene was introduced into anthracene by C-H direct arylation, enabling the synthesis of various bis(pentafluorophenyl)anthracene (DPA-F) derivatives. The high reactivity of the pentafluorobenzene C-H bond allows direct arylation for synthesizing DPA-F derivatives in a single step. The introduction of strong electron-withdrawing pentafluorophenyl groups provides the anthracene derivatives with n-type semiconducting properties, in contrast to the p-type properties of the parent DPAs. Among the synthesized compounds, 2,6-bis(pentafluorophenyl)anthracene shows a high electron mobility of 0.12±0.02 cm2 /Vs and an on/off ratio>106 in OFETs. The high crystallinity results in the smooth electron transport. This study provides a facile synthetic method for n-type semiconducting materials and insights into the molecular design of the positional effects of aromatic substituents on anthracene.

Risk and prognostic factors of invasive gastric cancer detection during surveillance endoscopy: Multi-institutional cross-sectional study.

OBJECTIVES: Esophagogastroduodenoscopy (EGD) is important for the detection of curable gastric cancer (GC). However, there are no appropriate surveillance data during routine endoscopic inspections. This study aimed to clarify the risk factors of pT1b or deeper GC detection during surveillance endoscopy. METHODS: This was a retrospective, multicenter, cross-sectional study conducted in 15 Japanese hospitals. We retrospectively analyzed patients with GC who had previously undergone surveillance endoscopy at each institution from January 2014 to March 2020. Patients who had undergone gastrectomy, non-infection of Helicobacter pylori (Hp), and those with intervals <3 months or >10 years from a previous endoscopy were excluded. RESULTS: In total, 1085 patients with GCs detected during surveillance endoscopy were enrolled. The multivariate logistic analysis revealed that current Hp infection (odds ratio [OR] 2.18; 95% confidence interval [CI] 1.50-3.16) and a surveillance interval of >1.5 years (OR 1.96; 95% CI 1.35-2.84) were independent risk factors for pT1b or deeper GC. The 5-year disease-specific survival (5y-DSS) rate of GC was significantly lower in patients with surveillance interval of >1.5 years than in those with surveillance interval of ≤1.5 years (93.7% vs. 98.3%, P < 0.001). Similarly, the 5y-DSS rate of GC was significantly lower in patients with active Hp infection than in those without (93.7% vs. 99.4%, P < 0.001). CONCLUSION: In this study, a surveillance interval of >1.5 years and current Hp infection were independent risk factors for detecting pT1b or deeper GC. Additionally, these factors were poor prognostic factors of the detected GC during surveillance endoscopy.

Demarcation Line Determination for Diagnosis of Gastric Cancer Disease Range Using Unsupervised Machine Learning in Magnifying Narrow-Band Imaging.

BACKGROUND AND AIMS: It is important to determine an accurate demarcation line (DL) between the cancerous lesions and background mucosa in magnifying narrow-band imaging (M-NBI)-based diagnosis. However, it is difficult for novice endoscopists. We aimed to automatically determine the accurate DL using a machine learning method. METHODS: We used an unsupervised machine learning approach to determine the DLs. Our method consists of the following four steps: (1) an M-NBI image is segmented into superpixels using simple linear iterative clustering; (2) the image features are extracted for each superpixel; (3) the superpixels are grouped into several clusters using the k-means method; and (4) the boundaries of the clusters are extracted as DL candidates. The 23 M-NBI images of 11 cases were used for performance evaluation. The evaluation investigated the similarity of the DLs identified by endoscopists and our method, and the Euclidean distance between the two DLs was calculated. For the single case of 11 cases, the histopathological examination was also conducted to evaluate the proposed system. RESULTS: The average Euclidean distances for the 11 cases were 10.65, 11.97, 7.82, 8.46, 8.59, 9.72, 12.20, 9.06, 22.86, 8.45, and 25.36. The results indicated that the proposed method could identify similar DLs to those identified by experienced doctors. Additionally, it was confirmed that the proposed system could generate pathologically valid DLs by increasing the number of clusters. CONCLUSIONS: Our proposed system can support the training of inexperienced doctors as well as enrich the knowledge of experienced doctors in endoscopy.

Endoscopic submucosal dissection for protruding Helicobacter pylori-negative mucosa-associated lymphoid tissue lymphoma of the stomach: a case report.

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas have various endoscopic appearances. We report a case of Helicobacter pylori-negative gastric MALT lymphoma with a protruding morphology similar to that of submucosal tumors. A 51-year-old man with a protruding tumor in the gastric cardia was referred to our hospital. Biopsy specimens showed no malignant epithelial tumors or lymphoid hyperplasia. Endoscopic submucosal dissection was performed and the patient was diagnosed with gastric MALT lymphoma. Lymphoma cells were present in the lamina propria mucosae and the submucosa under the non-atrophic fundic gland mucosa, with a feature of homogenous and monotonous growths, which was speculated to have resulted in a protruding morphology similar to that of submucosal tumors. Endoscopic submucosal dissection can be an alternative diagnostic option for gastric MALT lymphoma when the initial pathological diagnosis based on biopsy specimens is difficult.

Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients Aged 85 Years Old or Older Is Associated with a Good Prognosis Compared to Conservative Treatment without Any Invasive Procedure.

INTRODUCTION: Studies have reported the feasibility of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in elderly people with respect to both short- and long-term outcomes. As the elderly population in society increases, the requirement for managing super-elderly patients aged ≥85 years with EGC will also increase. This study aims to identify the long-term clinical outcomes of ESD for clinical T1N0 EGC in patients aged ≥85 years. METHODS: A total of 370 consecutive patients aged ≥85 years with clinical T1N0 EGC who were managed in 11 institutions were reviewed retrospectively. On the basis of treatment strategy, we compared the overall survival (OS) and disease-specific survival (DSS) after performing propensity score-matched analysis between patients undergoing ESD (ESD group) and those not undergoing treatment (conservative treatment group). The potential prognostic factors were also investigated in the propensity score-matched patients. RESULTS: After propensity score matching, we found that the 3-year OS and DSS rates were significantly higher in the ESD group than in the conservative treatment group (OS, 82.2% vs. 50.5%; p < 0.001; DSS, 100% vs. 80.1%; p = 0.008). Furthermore, ESD was identified as a significant factor for prolonged OS, whereas Charlson comorbidity index (CCI) ≥3 and prognostic nutritional index (PNI) <36.2 were associated with reduced OS. CONCLUSION: ESD was associated with improved OS in patients with clinical T1N0 EGC aged ≥85 years compared with the absence of treatment. Furthermore, CCI and PNI were helpful for patient selection.

Histone deacetylation regulates nucleotide excision repair through an interaction with the XPC protein.

The XPC protein complex plays a central role in DNA lesion recognition for global genome nucleotide excision repair (GG-NER). Lesion recognition can be accomplished in either a UV-DDB-dependent or -independent manner; however, it is unclear how these sub-pathways are regulated in chromatin. Here, we show that histone deacetylases 1 and 2 facilitate UV-DDB-independent recruitment of XPC to DNA damage by inducing histone deacetylation. XPC localizes to hypoacetylated chromatin domains in a DNA damage-independent manner, mediated by its structurally disordered middle (M) region. The M region interacts directly with the N-terminal tail of histone H3, an interaction compromised by H3 acetylation. Although the M region is dispensable for in vitro NER, it promotes DNA damage removal by GG-NER in vivo, particularly in the absence of UV-DDB. We propose that histone deacetylation around DNA damage facilitates the recruitment of XPC through the M region, contributing to efficient lesion recognition and initiation of GG-NER.

Linked Color Imaging and Blue Laser Imaging for the Diagnosis of Superficial Non-Ampullary Duodenal Epithelial Tumors.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate endoscopic findings using linked color imaging (LCI) and blue laser imaging (BLI) and to determine a diagnostic predictor for duodenal adenocarcinomas. METHODS: All consecutive patients who underwent endoscopic resection for superficial non-ampullary duodenal epithelial tumors (SNADETs) between October 2012 and June 2019 were enrolled in this study. Two highly experienced endoscopists investigated six morphological findings using both white light imaging and LCI and three magnifying endoscopic findings using magnifying BLI (M-BLI). RESULTS: A total of 90 patients with 110 SNADETs, including 87 adenocarcinomas and 23 adenomas, were analyzed in this study. Among the non-magnifying endoscopic findings, the presence of reddish color, orange color on LCI (orange color sign), lobulation, depression, and marginally white opaque substance were found significantly more frequently in adenocarcinomas than in adenomas (p = 0.015, p < 0.001, p = 0.048, p < 0.001, and p = 0.007, respectively). Among the magnifying endoscopic findings, a mixed microsurface pattern (MSP), irregular MSP, and irregular microvascular pattern were found significantly more frequently in adenocarcinomas than in adenomas (p < 0.001, p < 0.001, and p = 0.002, respectively). In the multivariate analysis of all endoscopic findings associated with adenocarcinoma, orange color sign (odds ratio [OR] 10.46; 95% confidence interval [CI]: 1.42-77.08; p = 0.021), mixed MSP (OR 4.66; 95% CI: 1.02-21.40; p = 0.048), and irregular MSP (OR 13.11; 95% CI: 1.41-121.99; p = 0.024) were independent predictors of adenocarcinoma. CONCLUSIONS: The presence of orange color sign on LCI and mixed/irregular MSP on M-BLI were independent diagnostic predictors that were frequently observed in duodenal adenocarcinoma.

A case of endoscopic submucosal dissection for neuroendocrine carcinoma of the esophagus with invasion to the muscularis mucosae.

Neuroendocrine carcinoma (NEC) of the esophagus at early-stage is very rare due to its rapidly progression. Here, we reported a case of esophageal NEC at early stage treated with endoscopic submucosal dissection (ESD). A 63-year-old man underwent esophagogastroduodenoscopy (EGD) and a lesion was detected in the thoracic esophagus. The preoperative diagnosis was squamous cell carcinoma (SCC) based on magnifying endoscopy; however, the pathological diagnosis was NEC with an invasion of muscularis mucosa accompanied by lymphovascular invasion. Adjuvant chemoradiotherapy was recommended after ESD; however, the patient did not accept additional treatments. The patient was alive with no recurrence 15 months after ESD. In this case, there were three malignant components among SCC, NEC, and adenocarcinoma with transitional areas among each component in the superficial part of the lesion.