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Molecular self-assembly under kinetic control is expected to yield nanostructures that are inaccessible through the spontaneous thermodynamic process. Moreover, time-dependent evolution, which is reminiscent of biomolecular systems, may occur under such out-of-equilibrium conditions, allowing the synthesis of supramolecular assemblies with enhanced complexities. Here we report on the capacity of a metastable porphyrin supramolecular assembly to differentiate into nanofibre and nanosheet structures. Mechanistic studies of the relationship between the molecular design and pathway complexity in the self-assembly unveiled the energy landscape that governs the unique kinetic behaviour. Based on this understanding, we could control the differentiation phenomena and achieve both one- and two-dimensional living supramolecular polymerization using an identical monomer. Furthermore, we found that the obtained nanostructures are electronically distinct, which illustrates the pathway-dependent material properties. Unlike in biomolecular systems, synthetic self-assembly is largely spontaneous, thus limiting the complexity and functionality of the materials one can create. Now, self-assembly under out-of-equilibrium conditions is demonstrated for a metastable supramolecular system. Differentiation of nanoparticles into nanofibres and nanosheets — with electronically distinct states — is achieved through kinetic control, illustrating pathway-dependent material properties.

Background and aimLinked color imaging (LCI) is a novel endoscopy system, which enhances slight differences in mucosal color. However, whether LCI is more useful than other kinds of image-enhanced endoscopy (IEE) in recognizing early gastric cancer remains unclear. This study aimed to evaluate LCI efficacy compared with the indigo carmine contrast method (IC), and blue laser imaging-bright (BLI-brt) in early differentiated-type gastric cancer recognition.MethodsWe retrospectively analyzed early differentiated-type gastric cancer, which were examined by all four imaging techniques (white light imaging, IC, LCI, BLI-brt) at Asahi University Hospital from June 2014 to November 2018. Both subjective evaluation (using ranking score: RS) and objective evaluation (using color difference score: CDS) were adopted to quantify early differentiated-type gastric cancer recognition.ResultsDuring this period, 87 lesions were enrolled in this study. Both RS and CDS of LCI were significantly higher (p < 0.01) than those of IC and BLI-brt. Both RS and CDS of BLI-brt had no significant difference compared with those of IC. Subgroup analysis revealed that LCI was especially useful in post-Helicobacter pylori eradication patients and flat or depressed lesions compared with IC and BLI-brt.ConclusionsLCI appears to be more beneficial for the recognition of early differentiated-type gastric cancer in endoscopic screenings than IC and BLI-brt from the middle to distant view.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees. A total of 143 participants, including 43 familial patients, 5 suspected patients, 3 sporadic nonfamilial patients, 22 unaffected familial members, and 70 unrelated controls, were screened for expanded abnormal pentanucleotide repeats in SAMD12, TNRC6A, RAPGEF2, YEAT2, MARCH6, and STARD7. DNA samples were analyzed using Southern blotting, long-range polymerase chain reaction (PCR), repeat-primed PCR, and long-range PCR followed by Southern blotting. Of the 51 individuals with clinically diagnosed or suspected BAFME, 49 carried a SAMD12 allele with an expanded TTTCA/TTTTA pentanucleotide repeat. Genetic and clinical anticipation was observed. As in previous reports, the one patient with homozygous mutant alleles showed more severe symptoms than the heterozygous carriers. In addition, screening for expanded pentanucleotide repeats in TNRC6A revealed that the frequency of expanded TTTTA repeat alleles in the BAFME group was significantly higher than in the control group. All patients who were clinically diagnosed with BAFME, including those in the original family reported by Yasuda, carried abnormally expanded TTTCA/TTTTA repeat alleles of SAMD12. Patients with BAFME also frequently carried a TTTTA repeat expansion in TNRC6A, suggesting that there may be unknown factors in the ancestry of patients with BAFME that make pentanucleotide repeats unstable.

BackgroundLong-term outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) have not been assessed in a large, multicenter cohort. We aimed to evaluate long-term outcomes of ESD for ESCC in a real-world setting.MethodsWe retrospectively recruited 659 patients who underwent ESD for ESCC at ten institutions from January 2007 to December 2015. Of these, 566 patients were analyzed and classified into three groups according to the pathologic invasion depth after ESD: epithelium/lamina propria mucosa (EP/LPM group: 454 patients), muscularis mucosa/submucosa invasion ≤ 200 μm below the inferior margin of the muscularis mucosa (MM/SM1 group: 81 patients), and submucosa invasion > 200 μm below the MM inferior margin (SM2 group: 31 patients).ResultsThe 5-year overall survival rates in the EP/LPM, MM/SM1, and SM2 groups were 92.6%, 80.0%, and 62.7%, respectively, while the 5-year disease-specific survival rates were 99.7%, 96.9%, and 88.3%, respectively. Multivariate analyses revealed that the invasion depth, Charlson Comorbidity Index (CCI), and prognostic nutritional index (PNI) were independent prognostic factors. Hazard ratios in the MM/SM1 and SM2 groups were 2.25 (95% confidence interval [CI] 1.04–4.83; P = 0.038) and 3.18 (95% CI 1.08–9.34; P = 0.036), respectively, compared to those in the EP/LPM group, while those for patients with a CCI ≥ 3 and PNI ≤ 47.75 were 3.25 (95% CI 1.79–5.89; P < 0.001) and 2.42 (95% CI 1.26–4.65; P = 0.008), respectively.ConclusionsThis study identified that invasion depth, presence of comorbid diseases and preoperative nutritional status are independent prognostic risk factors associated with ESCC patients undergoing ESD.

Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.

Medium-bandgap polymer donors (such as PBDB-T) and their derivatives are promising donor materials for organic photovoltaics (OPVs). In this study, we aimed to develop a facile synthetic approach for PBDB-T using a C–H/C–I direct arylation reaction in monomer synthesis and C–H/C–Br direct arylation for polymerization. Polycondensation and end-capping methods using direct arylation reactions have been established, enabling the synthesis of polymers without Br termini. The OPV performance of the synthesized polymer was evaluated and compared to that of a benchmark polymer. The synthesized polymer exhibited lower OPV performance than the benchmark polymer despite having similar molecular weights. Possible factors contributing to low OPV performance and future challenges include structural defects, impurities, and large molecular weight distribution.C–H/C–I direct arylation reactions for monomer synthesis and C–H/C–Br direct arylation polycondensation were investigated for the short-step synthesis of promising medium-bandgap polymers (PBDB-T) for OPV applications. Polycondensation and end-capping reactions using direct arylation have been established, enabling the synthesis of polymers without Br termini. The OPV performance of the synthesized polymer was lower than that of the benchmark polymer synthesized using the conventional method, despite having similar molecular weights. Possible factors for low OPV performance and future challenges include structural defects, impurities, and large molecular weight distribution.

BackgroundThe 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.MethodsWe 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.ResultsThe 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).ConclusionsAs 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.

Key messageFusarium yellows resistant and susceptible lines in Brassica rapa showed different salicylic acid responses; the resistant line showed a similar response to previous reports, but the susceptible line differed.Fusarium yellows caused by Fusarium oxysporum f. sp. conglutinans (Foc) is an important disease. Previous studies showed that genes related to salicylic acid (SA) response were more highly induced following Foc infection in Brassica rapa Fusarium yellows resistant lines than susceptible lines. However, SA-induced genes have not been identified at the whole genome level and it was unclear whether they were up-regulated by Foc inoculation. Transcriptome analysis with and without SA treatment in the B. rapa Fusarium yellows susceptible line ‘Misugi’ and the resistant line ‘Nanane’ was performed to obtain insights into the relationship between SA sensitivity/response and Fusarium yellows resistance. ‘Nanane’s up-regulated genes were related to SA response and down-regulated genes were related to jasmonic acid (JA) or ethylene (ET) response, but differentially expressed genes in ‘Misugi’ were not. This result suggests that Fusarium yellows resistant and susceptible lines have a different SA response and that an antagonistic transcription between SA and JA/ET responses was found only in a Fusarium yellows resistant line. SA-responsive genes were induced by Foc inoculation in Fusarium yellows resistant (RJKB-T23) and susceptible lines (RJKB-T24). By contrast, 39 SA-induced genes specific to RJKB-T23 might function in the defense response to Foc. In this study, SA-induced genes were identified at the whole genome level, and the possibility, the defense response to Foc observed in a resistant line could be mediated by SA-induced genes, is suggested. These results will be useful for future research concerning the SA importance in Foc or other diseases resistance in B. rapa.

Background/Objectives: This study aimed to identify specific endoscopic findings associated with the development of GC following successful H. pylori eradication. Methods: This prospective multicenter observational study included patients who underwent annual surveillance endoscopy after successful H. pylori eradication therapy between September 2013 and June 2019. Endoscopic findings were evaluated one year after eradication therapy and analyzed using the Kyoto Classification of Gastritis to identify factors associated with GC development. Results: A total of 465 patients were included, including 49 patients with GC and 416 patients without GC. At the initial endoscopic assessment (median, 0.96 years post-eradication), emergence of map-like redness and invisible regular arrangement of collecting venule (RAC) as independent predictors of GC (map-like redness: hazard ratio [HR], 2.561; 95% confidence interval [CI], 1.362–4.572; p = 0.003; invisible RAC: HR, 3.131; 95% CI, 1.078–9.091; p = 0.036). Patients with map-like redness or invisible RAC showed a significantly higher incidence of GC than those without map-like redness or invisible RAC (p < 0.001 and p < 0.001, respectively). Notably, map-like redness and visible RAC appeared in 13% and 28.4% of cases within the first year after eradication, respectively. Conclusions: Map-like redness and invisible RAC were identified as independent predictors of GC following H. pylori eradication and may serve as early predictive indicators, appearing within one year of successful eradication. This finding underscores the importance of early surveillance endoscopy in identifying patients at elevated risk for GC.

In this paper, the recent research progress on triphenylamine (TPA)-based donor-acceptor (D-A) amorphous polymers including our developed polymers is reviewed. TPA has three-dimensional branched structures and can provide D-A polymers containing D and A units in the main chain or side chain. The use of TPA-based amorphous polymers in the fabrication of organic photovoltaics (OPVs) offers great advantages over the use of a polycrystalline film in terms of high reproducibility of the OPV performance. The amorphous polymer design using TPA, therefore, indicates a promising direction for the development of new donor materials in OPVs.