Contribution of ADD3 and the HLA Genes to Biliary Atresia Risk in Chinese.

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10-11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10-4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.

Sugarcane Pulp Take-Out Containers Produce More Microparticles in Acidic Foods.

In the current study, the production of microparticles released from fifteen commercial sugarcane pulp (SCP) take-out containers into different food simulants under different conditions was investigated, where deionized water (DI water), 4% acetic acid (4% HAc), and 95% ethanol (95% EtOH) were used to simulate aqueous, acidic, and fatty foods, respectively. Results showed that compared with DI water and 95% EtOH, 4% HAc caused the degradation of sugarcane fibers, thereby releasing the highest number of microparticles. The overall migration values of the sugarcane pulp take-out containers in 4% HAc were above the prescribed limit of 10 mg/dm2. Furthermore, it was estimated that consumers may intake 36,400-231,700 microparticles in a take-out container at one time, of which the proportion of particles with a particle size between 10 and 500 µm was the highest, ranging from 26,470 to 216,060 items. Moreover, the Al and Fe are the main metals in these take-out containers, ranging between 35.16 and 1244.04 and 44.71 and 398.52 mg/kg, respectively, followed by Pb, Ti, and Sr. This study provides important information that the safety of both the production of microparticles and the metallic elements should be considered for SCP take-out containers when in contact with food.

Effect of neutralization treatment on properties of chitosan/bamboo leaf flavonoids/nano-metal oxide composite films and application of films in antioxidation of rapeseed oil.

Neutralization treatment improved the slow-release antioxidant food packaging function of chitosan (CS)/bamboo leaf flavone (BLF)/nano-metal oxides composite films. The film cast from the CS composite solution neutralized by KOH solution had good thermal stability. The elongation at break of the neutralized CS/BLF film was increased by about 5 times, which provided the possibility for its packaging application. After 24 h of soaking in different pH solutions, the unneutralized films swelled severely and even dissolved, while the neutralized films maintained the basic structure with a small degree of swelling, and the release trend of BLF conformed to the logistic function (R2 ≥ 0.9186). The films had a good ability to resist free radicals, which was related to the release amount of BLF and the pH of the solution. The antimicrobial neutralized CS/BLF/nano-ZnO film, like the nano-CuO and Fe3O4 films, were effective in inhibiting the increase in peroxide value and 2-thiobarbituric acid induced by thermal oxygen oxidation of rapeseed oil and had no toxicity to normal human gastric epithelial cells. Therefore, the neutralized CS/BLF/nano-ZnO film is likely to become an active food packaging material for oil-packed food, which can prolong the shelf life of packaged food.

Association analysis and functional follow-up identified common variants of JAG1 accounting for risk to biliary atresia.

Background: Biliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The Jagged1 (JAG1) gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in JAG1 with isolated BA risk in the Chinese Han population. Methods: We genotyped 31 tag single nucleotide polymorphisms covering the JAG1 gene region in 333 BA patients and 1,665 healthy controls from the Chinese population, and performed case-control association analysis. The expression patterns of JAG1 homologs were investigated in zebrafish embryos, and the roles of jag1a and jag1b in biliary development were examined by morpholino knockdown in zebrafish. Results: Single nucleotide polymorphisms rs6077861 [P Allelic = 1.74 × 10-4, odds ratio = 1.78, 95% confidence interval: 1.31-2.40] and rs3748478 (P Allelic = 5.77 × 10-4, odds ratio = 1.39, 95% confidence interval: 1.15-1.67) located in the intron region of JAG1 showed significant associations with BA susceptibility. The JAG1 homologs, jag1a and jag1b genes were expressed in the developing hepatobiliary duct of zebrafish, especially at 72 and 96 h postfertilization. Knockdown of both jag1a and jag1b led to poor biliary secretion, sparse intrahepatic bile duct network and smaller or no gallbladders compared with control embryos in the zebrafish model. Conclusion: Common genetic variants of JAG1 were associated with BA susceptibility. Knockdown of JAG1 homologs led to defective intrahepatic and extrahepatic bile ducts in zebrafish. These results suggest that JAG1 might be implicated in the etiology of BA.

Chemical contaminants from food contact materials and articles made from or containing wood and bamboo - a review.

Due to recently introduced 'so-called' bio- and plant-based friendly food contact materials and articles (FCM/FCA), some neglected safety issues need to be raised. In this review, potential chemical contaminants from FCM/FCA made from or containing wood and bamboo are presented. Sources, migration, and analytical issues in determining contaminants including intentionally and non-intentionally added substances (IAS and NIAS, respectively) are reviewed. Most of the contaminants are components from melamine-formaldehyde-resin (MFR), paints and coatings, preservatives, and bleaching agents. Tableware made of MFR containing bamboo fibres as a filler are not always suitable for use as tableware since harmful amounts of melamine and formaldehyde can migrate from the tableware into food and even accelerate the degradation of certain polymers with which they are mixed. In addition, in the EU bamboo in plastic FCM is not authorized under Regulation (EU) 10/2011. Paints and coatings used to provide surface coverage for bamboo and wooden articles also pose a risk of migration of heavy metals. Limits on preservatives in wood FCM are covered by legislation in many countries, nevertheless their contamination should not be ignored. Some wood species are considered 'toxic' or contain 'toxic' constituents that should not be used in contact with food, which are worth considering for legislation. IAS analyses in bamboo and wooden FCM is generally not a problem, but has proven to be more challenging for NIAS. Due to a complex mixture of substances contained in plant-based materials, there is a need to improve databases for non-target screening of such chemicals.

Lactate-driven macrophage polarization in the inflammatory microenvironment alleviates intestinal inflammation.

Background: Lactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation. Methods: RAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations. Results: The in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis. Conclusions: Lactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotesthe repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation.

Lactic acid in macrophage polarization: The significant role in inflammation and cancer.

Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.

Lycium barbarum polysaccharides ameliorate LPS-induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice.

In the present study, the anti-inflammatory effect of Lycium barbarum polysaccharide (LBP) and the possible molecular mechanism thereof were examined, so as to perceive the pharmacological action of LBP. With acute peritonitis in mice as the inflammatory model, the protective effect of LBP on peritonitis mice was evaluated by recording the effect of behavioral scores, studying the pathological damage of intestine and liver, and detecting the levels of inflammatory cytokines. Additionally, by establishing an lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, the effect of LBP on RAW264.7 cell phenotype and culture supernatant inflammatory markers was observed. Finally, the activation of inflammation-related target genes, such as iNOS, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, and IκBα, were further detected. The results reveal that pretreatment with LBP could decrease the behavioral score of inflammatory mice, inhibit the secretion of pro-inflammatory factors, and reduce liver and intestine injury. LBP can regulate the effect of lipopolysaccharide on the polarization of RAW264.7 cells, and reduce the production of NO and cytokines (TNF-α, IL-1ß, IL-6). Further, LBP pretreatment was found to be able to significantly reduce the expression of iNOS, TLR4, NF-κB p65, and IκBα in macrophages. The present research provides evidence that LBP exerts potential anti-inflammatory activity in LPS-induced RAW264.7 macrophages via inhibiting TLR4 and NF-κB inflammatory sites and improving the behavior score of peritonitis mice. PRACTICAL APPLICATIONS: In recent years, the number of deaths worldwide has continued to rise as a result of inflammation. Despite said rise in deaths, many synthetic drugs with anti-inflammatory properties are significantly expensive and also have a host of side effects. Thus, the development of new anti-inflammatory drugs derived from medicinal plants has broad application potential. As such, in the present study, lipopolysaccharide (LPS)-induced macrophages were used to establish inflammatory cell models to verify the anti-inflammatory effect of Lycium barbarum polysaccharides (LBP). Findings were made that LBP could reduce the expression levels of inflammatory cytokines and NO by regulating macrophage polarization and NF-κB translocation, and thus, could exert anti-inflammatory activity. In addition, by intraperitoneal injection of LPS to establish peritonitis mice models, LBP pretreatment was found to have significantly modified the behavioral score of mice, while decreasing the secretion of inflammatory factors and the damage to several organs. The present study provides a basis for further understanding the effects of LBP in acute inflammation.

Association Analysis of Variants of DSCAM and BACE2 With Hirschsprung Disease Susceptibility in Han Chinese and Functional Evaluation in Zebrafish.

Hirschsprung disease (HSCR) has a higher incidence in children with Down syndrome (DS), which makes trisomy 21 a predisposing factor to HSCR. DSCAM and BACE2 are close together on the HSCR-associated critical region of chromosome 21. Common variants of DSCAM and rare variants of BACE2 were implicated to be associated with sporadic HSCR. However, the submucosal neuron defect of DS mouse model could not be rescued by normalization of Dscam. We aimed to explore the contribution of DSCAM and BACE2 to the development of the enteric nervous system (ENS) and HSCR susceptibility. We genotyped 133 tag single-nucleotide polymorphisms (SNPs) in DSCAM and BACE2 gene region in 420 HSCR patients and 1,665 controls of Han Chinese. Expression of DSCAM and BACE2 homologs was investigated in the developing gut of zebrafish. Overexpression and knockdown of the homologs were performed in zebrafish to investigate their roles in the development of ENS. Two DSCAM SNPs, rs430255 (P Addtive = 0.0052, OR = 1.36, 95% CI: 1.10-1.68) and rs2837756 (P Addtive = 0.0091, OR = 1.23, 95% CI: 1.05-1.43), showed suggestive association with HSCR risk. Common variants in BACE2 were not associated with HSCR risk. We observed dscama, dscamb, and bace2 expression in the developing gut of zebrafish. Knockdown of dscama, dscamb, and bace2 caused a reduction of enteric neurons in the hindgut of zebrafish. Overexpression of DSCAM and bace2 had no effects on neuron number in the hindgut of zebrafish. Our results suggested that common variation of DSCAM contributed to HSCR risk in Han Chinese. The dysfunction of both dscams and bace2 caused defects in enteric neuron, indicating that DSCAM and BACE2 might play functional roles in the occurrence of HSCR. These novel findings might shed new light on the pathogenesis of HSCR.

Zizyphus jujuba cv. Muzao polysaccharides enhance intestinal barrier function and improve the survival of septic mice.

This study aimed to examine the role of Zizyphus jujuba cv. Muzao polysaccharides (ZJPs) in protecting intestinal barrier function and the survival of septic mice. The sepsis mouse model was generated through cecal ligation and puncture (CLP) to observe the effect of ZJPs on the function of the intestinal barrier in the context of sepsis. We observed the clinical symptoms and survival time of the mice and evaluated serum inflammatory cytokines, intestinal pathological changes and intestinal permeability. Moreover, tight junction (TJ) proteins and apoptosis-associated proteins in intestinal tissue were examined. Finally, TLR4/NF-κB pathway-related proteins were measured in all groups. The results showed that pretreatment with ZJPs improved clinical and histological scores and reduced intestinal barrier permeability, and the levels of proinflammatory factors were decreased. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice by ZJPs pretreatment. The current study provides evidence that ZJPs have the potential to protect intestinal barrier function and improve the survival of septic mice via the attenuation of TLR4/NF-κB inflammatory signaling. PRACTICAL APPLICATIONS: This study reports the potential protective effect of ZJPs against cecal ligation and puncture (CLP)-induced sepsis. Our data reveal that CLP induced damage to the gut mucosal barrier, inflammation, and apoptosis in intestinal tissues. However, pretreatment with ZJPs improved clinical and histological scores, reduced intestinal barrier permeability, and decreased the levels of proinflammatory factors in mice. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice after ZJPs pretreatment. These findings provide evidence that pretreatment with ZJPs has the potential to attenuate CLP-induced gut damage in mice by restraining inflammation and apoptosis via the attenuation of NF-κB signaling. It provides a basis for further study of ZJPs in sepsis.

In vitro digestion rate of fully gelatinized rice starches is driven by molecular size and amylopectin medium-long chains.

In current study, the effects of starch fine molecular structures on its in vitro digestibility at fully gelatinized stage were investigated. The digestion kinetics of 15 fully gelatinized rice starches were obtained and correlated with starch chain-length distributions and molecular size distributions. Both logarithm of slopes and parallel first-order kinetic model were applied to fit the digestion curves to a few kinetics-based parameters. Result showed there were two simultaneous digestion fractions (fast versus slow) for fully gelatinized rice starches. The rate constants of slowly-digestible fraction significantly correlated with starch molecular sizes, especially with that of amylopectin molecules. Hydrodynamically larger amylopectin molecules tend to contain more shorter branches but less long chains. This slows down the starch hydrolysis by α-amylase while the action of AMG is less antagonistically hindered, increasing overall digestion rate. This study provides important information for rice breeders and manufacturers to develop rice products with reduced starch digestibility.

Correlates of Symptom Burden of Hemodialysis Patients.

This cross-sectional study assessed the overall symptom burden, including the prevalence, frequency, severity, and distress of symptoms among hemodialysis patients, and explored the relationship between demographic characteristics, clinical variables, self-management, sense of coherence, social support, and symptom burden in these patients. Herein, a regression analysis was performed to determine associations with symptom burden. The mean score of symptom burden among the participants (n = 382) was 74.12, with an average number of 12 symptoms. The analysis revealed that self-management, sense of coherence, and social support were negatively associated with the overall symptom burden. The multiple regression model showed that 48.6% of the variance in symptom burden was explained by meaningfulness, emotional management, daily urine output, subjective support, gender, and manageability. These findings contribute to the knowledge of symptom burden among hemodialysis patients and some new predictors (self-management, sense of coherence, and social support) of their symptom burden.

Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung's Disease in Han Chinese Population.

Background and Aims: Hirschsprung's disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on CASQ2 and PLD1, and intergenic variants located between SLC4A7 and EOMES at 3p24.1, and between LINC01518 and LOC283028 at 10q11.21, were associated with HSCR susceptibility. To validate these associations with HSCR susceptibility, we performed a case-control study in a Han Chinese sample set. Methods: We selected four previously identified single nucleotide polymorphisms (SNPs) for replication, along with tag SNPs to cover the four associated regions. In total, 61 SNPs were genotyped in 420 HSCR patients and 1,665 healthy controls from the Han Chinese population. Results: None of the 14 tag SNPs in the CASQ2 gene region, including the previously associated rs9428225, showed an association with HSCR. Among the 24 tag SNPs from the SLC4A7-EOMES region at 3p24.1, rs2642925 [odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.10-1.79; P Additive = 0.007] and the previously associated SNP rs9851320 showed a suggestive association (OR = 1.22, 95% CI = 1.01-1.47; P Additive = 0.042). A non-synonymous SNP, rs2287579, in PLD1 showed a suggestive association with HSCR susceptibility (OR = 1.71, 95% CI = 1.18-2.46; P Additive = 0.004). Additionally, the previously associated PLD1 SNP rs12632766 showed a suggestive significance (OR = 1.20, 95% CI = 1.01-1.42, P Additive = 0.038). In the LINC01518-LOC283028 region at 10q11.21, three SNPs meet the study-wide significance threshold. Rs17153309 was the most associated SNP (OR = 1.60, 95% CI = 1.34-1.90; P Additive = 1.13 × 10-7). The previously associated SNP rs1414027 also showed significant association (OR = 1.43, 95% CI = 1.20-1.70, P Additive = 3.92 × 10-5). Two associated SNPs at 10q11.21 (rs1414027 and rs624804) were expression quantitative trait loci in digestive tract tissues from GTEx databases. Conclusions: Our results confirmed that variants of the LINC01518-LOC283028 region were associated with HSCR in the Han Chinese population. Additionally, the susceptibility of SNPs in the LINC01518-LOC283028 region were associated with the expression levels of nearby genes. These results provide new insight into the pathogenesis of HSCR.

A combined action of amylose and amylopectin fine molecular structures in determining the starch pasting and retrogradation property.

Starch fine molecular structures are of essentially important in determining its pasting and retrogradation properties. In this study, 10 different starches from various botanical sources were selected to investigate the combined action of amylose and amylopectin molecules in determining the starch physicochemical properties. Correlation between starch structural parameters with the pasting and retrogradation properties showed that amylose and amylopectin CLDs do not affect these properties in isolation. Such as, the amount of amylose long chains and amylopectin short chains are both positively correlated with the melting temperatures and enthalpy of retrograded starches. Furthermore, relatively longer amylose short to medium chains can result in higher trough and breakdown viscosity, while higher amount of amylopectin medium to long chains result in higher peak viscosity. The results help a better understanding of the importance of amylose and amylopectin fine molecular structures in determining starch functional properties.

Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility.

Biliary atresia (BA) is an idiopathic neonatal cholestatic disease. Recent genome-wide association study (GWAS) revealed that common variation of ADD3, GPC1, ARF6, and EFEMP1 gene was associated with BA susceptibility. We aimed to evaluate the association of these genes with BA in Chinese population. Twenty single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 340 BA patients and 1,665 controls. Three SNPs in ADD3 were significantly associated with BA, and rs17095355 was the top SNP (PAllele = 3.23×10-6). Meta-analysis of published data and current data indicated that rs17095355 was associated with BA susceptibility in Asians and Caucasians. Three associated SNPs were expression quantitative trait loci (eQTL) for ADD3. Two GPC1 SNPs in high linkage disequilibrium (LD) showed nominal association with BA susceptibility (PAllele = 0.03 for rs6707262 and PAllele = 0.04 for rs6750380), and were eQTL of GPC1. Haplotype harboring these two SNPs almost reached the study-wide significance (P = 0.0035). No association for ARF6 and EFEMP1 was found with BA risk in the current population. Our study validated associations of ADD3 and GPC1 SNPs with BA risk in Chinese population and provided evidence of epistatic contributions of genetic factors to BA susceptibility.

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We measured the ratio of δ13C and δ15N values to estimate the trophic level of main organisms based on a fisheries resource survey in coastal water of Lyusi fishing ground carried out in September 2018. The results showed that δ13C values of the main organisms ranged from -24.27‰ to -13.24‰, with an average of (-17.15±1.85)‰. The δ15N values ranged from 4.30‰ to 14.61‰, with an average of (11.21±1.90)‰. Results from cluster analysis demonstrated that the main organisms in the coastal water of Lyusi fishery ground could be divided into four trophic groups. The first group was consisted mainly by middle and small fishes, shrimps and other invertebrates. The second group included the small-sized fishes like Konosirus punctatus, Mugil cephalus, etc. and shrimps like Exopalaemon annandalei, Exopalamon carincauda, etc. The phytoplankton belonged to the third group. The fourth group was zooplankton. In the trophic spectrum, the trophic levels of fish, shrimps and crabs, shellfish were 3.2-4.7, 3.2-4.2 and 2.0-4.1, respectively. Most species belonged to the category of middle and high-level consumers. In this survey, the average trophic level of the same species in the coastal waters of Lyusi fishing ground was 0.6, which was higher than that in the East China Sea and Yellow Sea. There was niche overlap of most fish, shrimps and crabs. Those results indicated the growth environment and nutrient structure of most living organisms in this area were generally similar.

Indication for endoscopic treatment based on the risk of lymph node metastasis in patients with undifferentiated early gastric cancer.

BACKGROUND: Despite the risk of lymph node metastasis (LNM), the indications of endoscopic submucosal dissection (ESD) has expanded to undifferentiated type (UD-type) early gastric cancer (EGC). There is debate as to whether the endoscopic resection can be used. This study was conducted to evaluate risk factors for LNM in undifferentiated early gastric cancer, implications for the indication of the ESD so as to providing evidence for proper clinical management for UD-type EGC. METHOD: We retrospectively analyzed 203 patients with UD-type EGC who underwent gastrectomy for primary gastric adenocarcinoma between 2012 and 2017. We evaluated the relationship between the clinicopathological factors and the presence of LNM using univariable and multivariable logistic regression analyses. RESULTS: A total of 203 UD-type EGC patients were enrolled, and LNM was positive in 40 cases (19.7%). Multivariable logistic regression analysis identified three independent risk factors for LNM, the tumor size (≥2.0 cm, P < 0.001), depth of invasion (P < 0.001), and lymphatic vessel involvement (LVI, P < 0.001). LNM was observed in 5.9% patients without the three predictive factors in UD-type EGC, whereas 7.7% and 37.7% of patients with one and two risk factors had LNM, respectively. In contrast, the LNM rate was up to be 66.7% in patients with three factors. Of 41 patients satisfying the expanded indication of ESD, 3 patients (7.3%) showed LNM. LNM was not found in any of 12 patients with small intramucosal lesions (<1.0 cm) without LVI. CONCLUSIONS: LNM-related risk factors were tumor larger than 2.0 cm, submucosal invasion, and the presence of LVI in UD-type EGC. ESD alone may be sufficient treatment for the intramucosal UD-type EGC that is smaller than 1.0 cm in size. When endoscopically resected specimens show unexpectedly larger tumor size, unexpected submucosal and LVI than that determined at pre-ESD endoscopic diagnosis, an additional gastrectomy with lymphadenectomy should be considered.

The growth suppression effects of UV-C irradiation on Microcystis aeruginosa and Chlorella vulgaris under solo-culture and co-culture conditions in reclaimed water.

Harmful algal blooms (HABs) are serious problems in landscape waters sourced from reclaimed water. In this study, the suppression effects of UV-C irradiation on microalgal growth were researched to find a possible preventive approach. Microcystis aeruginosa and Chlorella vulgaris were exposed to UV-C irradiation and then cultured in real reclaimed water for 7-18 d. UV-C irradiation at 50-200 mJ cm-2 could inhibit the growth of M. aeruginosa, C. vulgaris, and both microalgae in co-culture for 3-14, 1-3, and 1-5 d respectively. In addition, UV-C irradiation could cause damage to the cell integrity. At 100-200 mJ cm-2 UV-C, the proportion of microalgal membrane damage (Pmd) in M. aeruginosa cells increased rapidly to 56%-76% from day 3, whereas that in C. vulgaris cells increased to 23%-62% within 3 d. The photochemical efficiency (represented by Y value) of the irradiated groups was negatively affected immediately after UV-C irradiation and recovered gradually during the incubation. The Y value of M. aeruginosa cells began to recover from days 3 to 14, whereas that of C. vulgaris recovered much more quickly, from days 0.1 to 1. Overall, the irradiation-induced suppressive effects on algal growth correlated positively with the UV-C doses. Because M. aeruginosa was more sensitive to UV-C irradiation, UV-C irradiation not only controlled the total biomass of the mixed algae but also selectively reestablished the dominance of the nontoxic C. vulgaris.

Characterizing the impact of starch and gluten-induced alterations on gelatinization behavior of physically modified model dough.

Gelatinization properties of physically modified starch-gluten matrices are often exclusively traced back to starch constitution without considering the state of gluten. Thus, gelatinization of model dough, combining reference (rS)/modified starch (mS) with reference (rG)/modified gluten (mG), was investigated using nuclear magnetic resonance and differential scanning calorimetry to relate structural alterations of biopolymers to their hydration properties. No differences were found in gelatinization onsets of model dough consisting of rS and mS combined with mG (starch: gluten = 50:50 (m/m)), although gelatinization enthalpy of mS mG (1.7 ±â€¯0.4 J/g dm) was significantly lowered in comparison to rS mG (2.2 ±â€¯0.2 J/g dm). Relaxation time T2 was significantly reduced for mG in comparison to rG, demonstrating a tighter water binding of mG. This suggests that reduced gelatinization enthalpy of modified starch-gluten matrices is caused by a destruction of crystal parts of modified starch and by a tighter water binding of modified gluten.

Identification of key genes and associated pathways in KIT/PDGFRA wild­type gastrointestinal stromal tumors through bioinformatics analysis.

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v­kit Hardy­Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet­derived growth factor receptor α (PDGFRA) wild­type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild­type GIST samples compared with KIT/PDGFRA mutant GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was conducted using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology­Based Annotation System (KOBAS) online tools, respectively. Protein­protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub­networks using the Molecular Complex Detection (MCODE) plug­in. Furthermore, enrichment analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were identified, including 238 upregulated genes primarily enriched in 'cell adhesion', 'biological adhesion', 'cell­cell signaling', 'PI3K­Akt signaling pathway' and 'ECM­receptor interaction', while the 308 downregulated genes were predominantly involved in 'inflammatory response', 'sterol metabolic process' and 'fatty acid metabolic process', 'small GTPase mediated signal transduction', 'cAMP signaling pathway' and 'proteoglycans in cancer'. A total of 25 hub genes were obtained and four modules were mined from the PPI network, and sub­networks also revealed these genes were primarily involved in significant pathways, including 'PI3K­Akt signaling pathway', 'proteoglycans in cancer', 'pathways in cancer', 'Rap1 signaling pathway', 'ECM­receptor interaction', 'phospholipase D signaling pathway', 'ras signaling pathway' and 'cGMP­PKG signaling pathway'. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild­type GISTs, including phosphatidylinositol­4,5­bisphosphate 3­kinase, catalytic subunit γ, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb­B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results.