Effects of the chain length of nonaromatic epoxy resins on thermomechanical and optical properties: experiments, and ab initio and molecular dynamics simulations.

Epoxy resin has been extensively used in the field of advanced electronic materials as an adhesive and encapsulant owing to its excellent material properties. However, recently, there has been a demand for further improvement in heat resistance, high transparency, environmental resistance, and enhanced handling properties for high-brightness light-emitting diodes. Conventional aromatic epoxy resins lack light resistance; therefore, a colorless and transparent epoxy resin without aromatic rings is desirable. In this study, tris(2,3-epoxypropyl) isocyanurate (TEPIC) was used as a nonaromatic epoxy resin, and three types of TEPIC with different side-chain lengths were prepared. The ultraviolet (UV)-visible absorption properties of TEPIC were evaluated using time-dependent density functional theory, and the practicality of the numerical prediction of light resistance was verified. TEPIC yields a UV absorbance spectrum with a lower intensity than those of conventional aromatic epoxy resins, suggesting that TEPIC is expected to have high light resistance. In addition, their thermomechanical properties and the influence of molecular structure were evaluated using both molecular dynamics (MD) simulations and experiments. The MD simulation and experimental results were in good agreement, indicating that the long side chains of TEPIC suppress triaxial deformation-induced failure and improve ductility instead of decreasing strength and stiffness. In addition, the longer side chains form a dense molecular structure with less free volume. These results indicate that numerical approaches can be used to predict various properties of epoxy resins and interpret them from the molecular structure. Accordingly, these approaches can be used to aid the material development process.

High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer.

INTRODUCTION: The tumor microenvironment (TME) in colorectal cancer (CRC) includes the gut microbiome, immune cells, angiogenic factors, and fibroblasts and plays a major role in cancer progression. The Immunoscore (IS) is based on tumor infiltration by immune cells that are known prognostic biomarkers for CRC. However, the interrelation between the IS, microbiome, and other TME factors in human CRC remains unclear. PATIENTS AND METHODS: A cohort of 94 patients with CRC was examined at the Shiga University of Medical Science Hospital in Japan. The expression levels of CD3, CD8, CD31, and alpha-smooth muscle actin (α-SMA) in the primary tumor were evaluated by immunohistochemistry. The IS was calculated based on the results of the CD3 and CD8 staining assays. Microbiomes in patients with CRC were examined by amplicon sequencing. RESULTS: The expression levels of α-SMA and tumor-infiltrating lymphocytes in patients with CRC were negatively correlated (P = 0.006). A high IS was associated with high abundance of Lachnospiraceae in the microbiomes of patients with CRC. CONCLUSION: Lymphocyte infiltration into the primary tumor was marked by reduced density of cancer-associated fibroblasts and enrichment of the Lachnospiraceae family in the gut microbiome, which may influence CRC progression.

Stability and Structural Analysis Using Small-Angle Neutron Scattering for Foam of Homogeneous Polyoxyethylene-Type Nonionic Surfactants with Multibranched Chains.

Small-angle neutron scattering can provide insight into the microstructure of the surfactant-stabilized foam. In this study, small-angle neutron scattering in combination with other techniques was employed to determine the microstructure of the foams stabilized using novel homogeneous polyoxyethylene (EO) alkyl ether-type nonionic surfactants with multibranched double chains (bC7-bC9EO12). Similarly, homogeneous EO-type nonionic surfactants with linear double chains (C8-C8EO12) and a linear single chain (C18EO12) were used. bC7-bC9EO12 and C8-C8EO12 surfactants with branched hydrophobic chains or double chains increased the foam stability and suppressed the draining. Furthermore, they formed rod-like micelles, and C18EO12 formed spherical micelles in the bulk solution. The foam film containing the plateau border contained micelles identical with those found in the bulk solution. For bC7-bC9EO12 and C8-C8EO12, the average radius of the bubbles immediately after foaming was of the order of hundreds of µm. Finally, these radii grew to the order of thousands of µm. Thus, a significant correlation was observed between the micellar structure and the stability of these foams.

Altered gut microbiota in patients with small intestinal bacterial overgrowth.

BACKGROUND AND AIM: Small intestinal bacterial overgrowth (SIBO) is diagnosed by using quantitative culture of duodenal aspirates and/or a hydrogen breath test. However, few studies have analyzed bacterial microbiota in Japanese patients with SIBO. METHODS: Twenty-four patients with any abdominal symptoms and suspected SIBO were enrolled. Quantitative culture of duodenal aspirates and a glucose hydrogen breath test were performed on the same day. SIBO was diagnosed based on a bacterial count ≥ 103  CFU/mL or a rise in the hydrogen breath level of ≥ 20 ppm. The composition of the duodenal microbiota was analyzed by 16S rRNA gene sequencing. RESULTS: Small intestinal bacterial overgrowth was diagnosed in 17 of the 24 patients (71%). The positive rates for the hydrogen breath test and quantitative culture of duodenal aspirates were 50% and 62%, respectively. Patients with SIBO showed significantly reduced α-diversity compared with non-SIBO patients, and analysis of ß-diversity revealed significantly different distributions between SIBO and non-SIBO patients. In addition, the intestinal microbiome in SIBO patients was characterized by increased relative abundance of Streptococcus and decreased relative abundance of Bacteroides compared with non-SIBO patients. CONCLUSIONS: Duodenal dysbiosis was identified in patients with SIBO and may play a role in the pathophysiology of SIBO.

Lipopolysaccharide O structure of adherent and invasive Escherichia coli regulates intestinal inflammation via complement C3.

Gut dysbiosis associated with intestinal inflammation is characterized by the blooming of particular bacteria such as adherent-invasive E. coli (AIEC). However, the precise mechanisms by which AIEC impact on colitis remain largely unknown. Here we show that antibiotic-induced dysbiosis worsened chemically-induced colitis in IL-22-deficient mice, but not in wild-type mice. The increase in intestinal inflammation was associated with the expansion of E. coli strains with genetic and functional features of AIEC. These E. coli isolates exhibited high ability to out compete related bacteria via colicins and resistance to the host complement system in vitro. Mutation of wzy, the lipopolysaccharide O polymerase gene, rendered AIEC more sensitive to the complement system and more susceptible to engulfment and killing by phagocytes while retaining its ability to outcompete related bacteria in vitro. The wzy AIEC mutant showed impaired fitness to colonize the intestine under colitic conditions, but protected mice from chemically-induced colitis. Importantly, the ability of the wzy mutant to protect from colitis was blocked by depletion of complement C3 which was associated with impaired intestinal eradication of AIEC in colitic mice. These studies link surface lipopolysaccharide O-antigen structure to the regulation of colitic activity in commensal AIEC via interactions with the complement system.

The anti-inflammatory and protective role of interleukin-38 in inflammatory bowel disease.

Interleukin (IL)-38 exerts an anti-inflammatory function by binding to several cytokine receptors, including the IL-36 receptor. In this study, we evaluated IL-38 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and investigated its functions. IL-38 mRNA expression in endoscopic biopsy samples was evaluated using quantitative PCR. IL-38 protein expression was analyzed using immunohistochemical technique. Dextran sulfate sodium-induced colitis was induced in C57BL/6 background IL-38KO mice. The IL-38 mRNA and protein expression were enhanced in the active mucosa of ulcerative colitis, but not in Crohn's disease. The ratio of IL-36γ to IL-38 mRNA expression was significantly elevated in the active mucosa of UC patients. Immunofluorescence staining revealed that B cells are the major cellular source of IL-38 in the colonic mucosa. IL-38 dose-dependently suppressed the IL-36γ-induced mRNA expression of CXC chemokines (CXCL1, CXCL2, and CXCL8) in HT-29 and T84 cells. IL-38 inhibited the IL-36γ-induced activation of nuclear-factor kappa B (NF-κB) and mitogen-activated protein kinases in HT-29 cells. DSS-colitis was significantly exacerbated in IL-38KO mice compared to wild type mice. In conclusion, IL-38 may play an anti-inflammatory and protective role in the pathophysiology of IBD, in particular ulcerative colitis, through the suppression of IL-36-induced inflammatory responses.

The Comparison of Fecal Microbiota in Left-Side and Right-Side Human Colorectal Cancer.

INTRODUCTION: Microbiomes play a vital role in the development and progression of cancer. The clinical status, including prognosis, genetic mutations, and sensitivity to chemotherapy, differs depending on the location of colorectal cancer (CRC); however, the association between gut microbiota and the location of CRC is not entirely understood. This study was conducted to evaluate the differences in the gut microbiota in patients with CRC according to the location of the tumor. METHODS: Fifty-six patients who underwent surgery for CRC between August 2018 and November 2019 were included in the study. Three patients who had received neoadjuvant therapy or antibiotic treatment within 1 month before surgery were excluded. The metagenomes of microbiota in preoperative feces were assessed using the V3-V4 region of 16s rRNA amplicon sequences. RESULTS: The beta diversity of the Bray-Curtis distance was significantly higher in left-sided than in right-sided CRC. Fusobacterium predominated in left-sided CRC according to the linear discriminant analysis effect size method. Blautia, Eryspelotrichales, Holdemanella, Faecalibacterium, Subdoligranulum, and Dorea constituted the dominant intestinal flora in right-sided CRC. Pathway analysis revealed that L-lysine fermentation and cob(II)yrinate a,c-diamide biosynthesis I were predominant in left-sided CRC. DISCUSSION: This study demonstrated that fecal microbiota in left-sided CRC constitutionally and functionally differ from those in right-side CRC. These results will help to elucidate the biological differences according to tumor location and develop treatments for human CRC.

Elemental diet induces alterations of the gut microbial community in mice.

The aim of the present study was to investigate elemental diet (ED)-induced alteration of the fecal and mucosal microbiome in mice. The control group was fed a normal chow and the ED group was fed normal chow containing 50% w/w Elental® (EA Pharma, Tokyo, Japan) for 28 days. Fecal and mucosal microbiome were analyzed using 16S rRNA gene sequencing. In the fecal samples, the observed species, an index for microbial richness, was significantly decreased in the ED group. Principal coordinate analysis revealed that there were significant compositional differences between the control and ED groups (PERMANOVA p = 0.0007 for unweighted and p = 0.002 for weighted UniFrac distance, respectively). In contrast, there was no significant difference in the overall structure of mucosal microbiome between the control and ED groups. In the fecal samples, abundance of the genera Adlercreutzia, Akkermansia, Streptococcus, Helicobacter, Coprobacillus and Coprococcus was significantly reduced in the ED group compared to the control group. Abundance of the genera Lactobacillus and Staphylococcus was significantly increased in the ED group. In a functional analysis using PICRUSt software, ED altered various pathways involved in amino acid metabolism of the gut microbiome. In conclusion, ED caused a reduction in bacterial diversity and altered metabolic functions.

Astaxanthin, a xanthophyll carotenoid, prevents development of dextran sulphate sodium-induced murine colitis.

Astaxanthin is a xanthophyll carotenoid, which possesses strong scavenging effect on reactive oxygen species. In this study, we examined the effect of astaxanthin on dextran sulfate sodium (DSS)-induced colitis in mice. Experimental colitis was induced by the oral administration of 4% w/v DSS in tap water in C57BL/6J mice. Astaxanthin was mixed with a normal rodent diet (0.02 or 0.04%). Astaxanthin significantly ameliorated DSS-induced body weight loss and reduced the disease activity index. The ameliorating effects was observed in a dose-dependent manner. Immunochemical analyses showed that astaxanthin markedly suppressed DSS-induced histological inflammatory changes (inflammatory cell infiltration, edematous changes and goblet cell depletion). Plasma levels of malondialdehyde and 8-hydroxy-2-deoxyguanosine were significantly reduced by the administration of 0.04% astaxanthin. Astaxanthin significantly suppressed the mucosal mRNA expression of IL-1ß, IL-6, TNF-α, IL-36α and IL-36γ. Astaxanthin blocked the DSS-induced translocation of NF-κB p65 and AP-1 (c-Jun) into the nucleus of mucosal epithelial cells, and also suppressed DSS-induced mucosal activation of MAPKs (ERK1/2, p38 and JNK). In conclusion, astaxanthin prevented the development of DSS-induced colitis via the direct suppression of NF-κB, AP-1 and MAPK activation. These findings suggest that astaxanthin is a novel candidate as a therapeutic option for the treatment of inflammatory bowel disease.

Mesoscopic Heterogeneity in Pore Size of Supramolecular Networks.

There has been a considerable interest in developing new types of gels based on a network of fibrous aggregate composed of low molecular weight gelators, also known as supramolecular gels (SMGs). Unlike conventional polymer gels with chemical cross-linking, the network formation in SMGs does not involve any covalent bonds. Thus, the network in SMGs has been often regarded as homogenous or less heterogeneous in comparison with that in chemically cross-linked polymer gels. In this study, we have experimentally verified the existence of the network heterogeneity even in SMGs. The thermal motion of probe particles in SMGs, which were prepared from aqueous dispersions of gelators having a different number of peptide residues, PalGH, PalG2H, and PalG3H, was tracked. The gels were spatially heterogeneous in terms of the network pore size, as evidenced by the variation in the particle motion depending on the location, at which a particle existed. With varying particle size, it was found that the characteristic length scale of the heterogeneity was in the order of (sub)micrometers and was smaller in the order of the PalG2H, PalG3H, and PalGH gels.

Ameliorating effects of bortezomib, a proteasome inhibitor, on development of dextran sulfate sodium-induced murine colitis.

We examined the effect of bortezomib, a proteasome inhibitor, on the development of dextran sulfate sodium (DSS)-induced colitis in mice. DSS-colitis was induced by the administration of 3% DSS in water in C57BL/6J mice. Bortezomib was intraperitoneally administered daily for 9 days from the start of DSS. Ubiquitination of IκBα was evaluated by immunoblot. Bortezomib significantly ameliorated DSS-induced body weight loss and reduced the disease activity. The translocation of NF-κBp65 into the nucleus was markedly suppressed in the DSS + bortezomib group compared to the DSS group, but this difference was not detected in submucosal tissue. Ubiquitinated IκBα in the cytoplasm of colon epithelial cells was increased in the DSS + bortezomib group compared to the DSS group. In HT-29 cells, bortezomib blocked tumor necrosis factor-α (TNF-α)-induced nuclear translocation of NF-κB and this was accompanied by an increase in ubiquitinated IκBα in the cytoplasm. The mRNA expression of inflammatory mediators in colonic epithelial cells was significantly reduced by the treatment of bortezomib. Bortezomib inhibited the nuclear translocation of NF-κB in colonic epithelial cells by suppressing the degradation of IκBα and contributed to an improvement in DSS colitis. Our study suggests that bortezomib may be a new treatment option for IBD.

Evolution of heterogeneity accompanying sol-gel transitions in a supramolecular hydrogel.

When a peptide amphiphile is dispersed in water, it self-assembles into a fibrous network, leading to a supramolecular hydrogel. When the gel is physically disrupted by shaking, it transforms into a sol state. After aging at room temperature for a while, it spontaneously returns to the gel state, called sol-gel transition. However, repeating the sol-gel transition often causes a change in the rheological properties of the gel. To gain a better understanding of the sol-gel transition and its reversibility, we herein examined the thermal motion of probe particles at different locations in a supramolecular hydrogel. The sol obtained by shaking the gel was heterogeneous in terms of the rheological properties and the extent decreased with increasing aging time. This time course of heterogeneity, or homogeneity, which corresponded to the sol-to-gel transition, was observed for the 1st cycle. However, this was not the case for the 2nd and 3rd cycles; the heterogeneity was preserved even after aging. Fourier-transform infrared spectroscopy, small-angle X-ray scattering, and atomic force and confocal laser scanning microscopies revealed that, although the molecular aggregation states of amphiphiles both in the gel and sol remained unchanged with the cycles, the fibril density diversified to high and low density regions even after aging. The tracking of particles with different sizes indicated that the partial mesh size in the high density region and the characteristic length scale of the density fluctuation were smaller than 50 nm and 6 µm, respectively.

Modulation of physical properties of supramolecular hydrogels based on a hydrophobic core.

We demonstrate herein the variation in viscoelastic properties of supramolecular hydrogels (SMGs) composed of two amphiphiles, N-Palmitoyl-Gly-His (PalGH) and sodium palmitate (PalNa). PalGH molecules in water form lamellar-like assemblies, which stack into sheet-shaped aggregates, resulting in the evolution of three-dimensional network structures. Once PalNa is added to PalGH, the alkyl groups of PalNa incorporate themselves into the hydrophobic cores of PalGH lamellar-like assemblies, resulting in a change in the assembly from lamellar-like to fibrous micelle-like. Consequently, sheet-shaped aggregates turn into flexible fibrils, which form bundles, resulting in network structures. Mixed hydrogel network structures differ in morphology from those in homogenous PalGH and PalNa hydrogels. Changes in the network structure eventually alter the bulk viscoelastic properties of hydrogels. These results demonstrate that the viscoelastic properties of supramolecular hydrogels can be tuned by controlling the aggregation states.

Sol-gel transition accelerated by the co-assembly of two components in supramolecular hydrogels.

N-Palmitoyl-Gly-His (PalGH) and glycerol 1-monopalmitate (GMP) in water co-assembled into fibrils with twisted ribbon structures and formed a homogeneous network, resulting in gel formation. Shaking the gel easily broke the fibril network leading to a sol in which high and low fibril density regions exist. After a period at room temperature, the higher density regions became interconnected. The spontaneous sol-gel transition did not take place for a gel made from only PalGH. Also, during the transition, the aggregation state of the co-assembly remained unchanged at a molecular level, unlike the fibril network. Thus, it can be claimed that the sol-gel transition is not associated with the assembled molecular configuration, but with the change in the fibril network. This knowledge might be useful for understanding and controlling sol-gel transition, thereby leading to the design and functionalization of hydrogels.

Relapsing sclerosing mesenteritis with multiple strictures of the small intestine.

Sclerosing mesenteritis (SM) is a rare disorder that involves the mesenteric adipose tissue with chronic fibrosing inflammation. Few reports mention the natural history of severe SM cases. Here, we report a severe and relapsing SM case in which a long-term natural history could be followed. The patient had undergone surgery for small bowel stenosis of unknown cause 10 years earlier. He had stopped visiting the hospital at his discretion. He was admitted to the hospital 10 years later due to recurrent symptoms, and a close examination revealed multiple small intestinal strictures; thus, surgery was performed again. The pathological results revealed that the patient had SM, corticosteroid administration dramatically improved his symptoms, and he has maintained remission for a long time.

A case of early gastric cancer with metastatic recurrence following curative endoscopic submucosal dissection.

A 70-year-old man was diagnosed with early gastric cancer with ulcerative findings. Endoscopic submucosal dissection as an absolute indication was performed, and en bloc resection was achieved. Pathological examination revealed a well-differentiated adenocarcinoma, 3 × 2 mm in size, intramucosal, with an ulcerative scar, no lymphovascular invasion, and a tumor-free margin. We diagnosed it as a curative resection and followed up with annual endoscopy. Sixteen months after endoscopic submucosal dissection, esophagogastroduodenoscopy revealed a singular ulcer scar; however, serum carcinoembryonic antigen level was elevated. Computed tomography scan showed wall thickening of the gastric antrum and an irregular mass on the dorsal side. Additionally, 18F-fluorodeoxyglucose positron emission tomography/coomputed tomography showed 18F-fluorodeoxyglucose uptake in the gastric antrum, irregular mass, and liver. Endoscopic ultrasonography revealed an internally heterogeneous mass in the gastric antrum region extending from the submucosal layer to the muscularis propria layer. Using an endoscopic ultrasonography-guided fine needle biopsy with a 22-gauge needle for the mass, we diagnosed local recurrence with the submucosal tumor-like appearance, lymph node metastasis, and liver metastases. Unfortunately, the patient died of gastric cancer 3 months after the diagnosis. Here, we report a rare case of local recurrence in the submucosal layer, lymph node metastasis, and liver metastases 16 months after curative endoscopic submucosal dissection.

Palliative stenting for malignant colorectal stenosis in the elderly.

Objectives: Self-expandable metal stents are widely used for the treatment of malignant colorectal stenosis (MCS). In elderly individuals with MCS, self-expandable metal stents are often used as a palliative treatment, but prophylactic stent placement is not recommended. We investigated the efficacy and safety of self-expandable metal stents for the elderly in a palliative setting, specifically in a prophylactic setting. Methods: Elderly patients with MCS who received a palliative stent (the stent group) or palliative stoma (the stoma group) were retrospectively enrolled between April 2017 and June 2022, and the prognosis and complication rates were assessed. Additionally, patients in the stent group were divided into symptomatic and asymptomatic subgroups, and prognosis, stent patency, and complication rates were evaluated. Results: During the study period, 31 patients with a mean age of 85.4 years and 12 patients with a mean age of 82.0 years were enrolled in the stent and stoma groups, respectively. While overall survival and complication rates were comparable, the length of hospital stay was significantly shorter in the stent group. Of the 31 patients in the stent group, 16 asymptomatic patients received prophylactic stenting, which was not associated with increased complication rates. Conclusions: Palliative stents for MCS appear to be effective and safe even in the elderly, and thus, prophylactic stents can be considered for asymptomatic patients.

Adherent-invasive E. coli - induced specific IgA limits pathobiont localization to the epithelial niche in the gut.

Background and aim: Adherent-invasive E. coli (AIEC) has been identified as a pathobiont associated with Crohn's disease (CD), that prefers to grow in inflammatory conditions. Although the colonization by AIEC is implicated in the progression of the disease and exacerbates inflammation in murine colitis models, the recognition and response of host immunity to AIEC remains elusive. Methods: Antibiotic treated female C57BL/6 mice were inoculated by commensal E. coli and LF82 AIEC strains. Luminal-IgA fractions were prepared from feces and their binding to AIEC and other strains was assessed to confirm specificity. IgA binding to isogenic mutant strains was performed to identify the functional molecules that are recognized by AIEC specific IgA. The effect of IgA on epithelial invasion of LF82 strain was confirmed using in vitro invasion assay and in vivo colonization of the colonic epithelium. Results: Persistent colonization by AIEC LF82 induced secretion of luminal IgA, while commensal E. coli strain did not. Induced anti-LF82 IgA showed specific binding to other AIEC strains but not to the commensal, non-AIEC E. coli strains. Induced IgA showed decreased binding to LF82 strains with mutated adhesin and outer membrane proteins which are involved in AIEC - epithelial cell interaction. Consistently, LF82-specific IgA limited the adhesion and invasion of LF82 in cultured epithelial cells, which seems to be required for the elimination in the colonic epithelium in mice. Conclusion: These results demonstrate that host immunity selectively recognizes pathobiont E. coli, such as AIEC, and develop specific IgA. The induced IgA specific to pathobiont E. coli, in turn, contributes to preventing the pathobionts from accessing the epithelium.

Update on gut microbiota in gastrointestinal diseases.

The human gut is a complex microbial ecosystem comprising approximately 100 trillion microbes collectively known as the "gut microbiota". At a rough estimate, the human gut microbiome contains almost 3.3 million genes, which are about 150 times more than the total human genes present in the human genome. The vast amount of genetic information produces various enzymes and physiologically active substances. Thus, the gut microbiota contributes to the maintenance of host health; however, when healthy microbial composition is perturbed, a condition termed "dysbiosis", the altered gut microbiota can trigger the development of various gastrointestinal diseases. The gut microbiota has consequently become an extremely important research area in gastroenterology. It is also expected that the results of research into the gut microbiota will be applied to the prevention and treatment of human gastrointestinal diseases. A randomized controlled trial conducted by a Dutch research group in 2013 showed the positive effect of fecal microbiota transplantation (FMT) on recurrent Clostridioides difficile infection (CDI). These findings have led to the development of treatments targeting the gut microbiota, such as probiotics and FMT for inflammatory bowel diseases (IBD) and other diseases. This review focuses on the association of the gut microbiota with human gastrointestinal diseases, including CDI, IBD, and irritable bowel syndrome. We also summarize the therapeutic options for targeting the altered gut microbiota, such as probiotics and FMT.