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Reverse osmosis (RO) membranes are becoming popular as energy saving and environmentally friendly materials for the desalination of water. Toward the rational design of RO membranes, we performed contrast-variation neutron scattering measurements and atomistic molecular dynamics (MD) simulations on polyamide/water systems with various water contents and deuteration ratios. The experimental and computational structure factors showed good agreement for all the systems examined. The structure of the water-rich polyamide/water system obtained from MD calculation showed that the water clusters are well connected to each other, and a relatively large number of water molecules are present at a distance over 3 A from the polyamide. The partial radial distribution functions were calculated, and strong interactions were observed between water and the carboxyl group in polyamide. Thus, the water permeability of the RO membrane can be expected to improve when more carboxyl groups are introduced. In addition, the polyamide–polyamide interaction was found to be equal to or smaller than the polyamide–water interactions and relatively weak in the water-rich system. Reverse osmosis membranes have been playing a main role for the desalination of water in the world. Hydration structure of polyamide functional layer of the membrane was studied via neutron scattering and atomistic molecular dynamics simulations. Experimental and computational structure factors, S(Q), of the polyamide/water system showed good agreement. Water clusters in water-rich system were well connected to each other and formed channel-like structure. Polyamide–water interactions and polyamide-polyamide interactions, which are thought to be important to enhance the performance of the membranes, were examined in detail.

Background Few studies have investigated the burst pressure of side-to-side anastomoses comparing different stapling devices that are commercially available. Objectives We conducted side-to-side anastomoses with a variety of staplers and compared burst pressure in the crotch of the anastomoses. Setting Nagoya City East Medical Center. Methods We conducted side-to-side anastomoses with 9 staplers with different shapes and forms. Fresh pig small intestines were used. A side-to-side anastomosis was performed between 2 intestine specimens using a linear stapler. The burst pressure of the anastomosis was recorded. Results In total, 45 staplers were used for this experiment. The site of leakage in all cases was the crotch. Regarding the influence of the number of staple rows, the burst pressure in 3-row staplers was significantly higher than in 2-row staplers. With regard to the relationship between staple height and burst pressure, staples with a height slightly shorter than the intestinal thickness showed the highest burst pressure. In a comparison of staplers with uniform staple heights and stamplers with staples of 3 different heights, the latter had significantly lower burst pressures. Neoveil significantly increased the burst pressure in the crotch and contributed to the highest burst pressure of all the staplers used in this experiment. Conclusions In this experiment, we defined the important factors that influence burst pressure at the crotch of a stapled, side-to-side anastomosis. These factors include the number of staple rows, the height of the staple compared with the thickness of the tissue, uniformity of staple height, and reinforcement of the staple line. In any surgical case requiring intestinal anastomosis, selection of a stapler is a critical step.

Objective— Abdominal aortic aneurysm (AAA) is an increasingly prevalent and ultimately fatal disease with no effective pharmacological treatment. Because matrix degradation induced by vascular inflammation is the major pathophysiology of AAA, attenuation of this inflammation may improve its outcome. Previous studies suggested that miR-33 (microRNA-33) inhibition and genetic ablation of miR-33 increased serum high-density lipoprotein cholesterol and attenuated atherosclerosis. Approach and Results— MiR-33a-5p expression in central zone of human AAA was higher than marginal zone. MiR-33 deletion attenuated AAA formation in both mouse models of angiotensin II– and calcium chloride–induced AAA. Reduced macrophage accumulation and monocyte chemotactic protein-1 expression were observed in calcium chloride–induced AAA walls in miR-33 −/− mice. In vitro experiments revealed that peritoneal macrophages from miR-33 −/− mice showed reduced matrix metalloproteinase 9 expression levels via c-Jun N-terminal kinase inactivation. Primary aortic vascular smooth muscle cells from miR-33 −/− mice showed reduced monocyte chemotactic protein-1 expression by p38 mitogen-activated protein kinase attenuation. Both of the inactivation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were possibly because of the increase of ATP-binding cassette transporter A1 that is a well-known target of miR-33. Moreover, high-density lipoprotein cholesterol derived from miR-33 −/− mice reduced expression of matrix metalloproteinase 9 in macrophages and monocyte chemotactic protein-1 in vascular smooth muscle cells. Bone marrow transplantation experiments indicated that miR-33–deficient bone marrow cells ameliorated AAA formation in wild-type recipients. MiR-33 deficiency in recipient mice was also shown to contribute the inhibition of AAA formation. Conclusions— These data strongly suggest that inhibition of miR-33 will be effective as a novel strategy for treating AAA.

Mouse acidic mammalian chitinase (AMCase) degrades chitin with highest efficiency at pH 2.0 and is active up to pH 8.0. Here, we report that mouse AMCase also exhibits transglycosylation activity under neutral conditions. We incubated natural and artificial chitin substrates with mouse AMCase at pH 2.0 or 7.0 and analyzed the resulting oligomers using an improved method of fluorescence assisted carbohydrate electrophoresis. Mouse AMCase produces primarily dimers of N-acetyl-D-glucosamine [(GlcNAc)2] under both pH conditions while generating transglycosylated (GlcNAc)3 primarily at pH 7.0 and at lower levels at pH 2.0. These results indicate that mouse AMCase catalyzes hydrolysis as well as transglycosylation and suggest that this enzyme can play a novel role under physiological conditions in peripheral tissues, such as the lungs. This article is protected by copyright. All rights reserved.

// Hideyuki Ishiguro 1, * , Tomotaka Okubo 1, * , Yoshiyuki Kuwabara 1 , Masahiro Kimura 1 , Akira Mitsui 1 , Nobuyoshi Sugito 1 , Ryo Ogawa 1 , Takeyasu Katada 1 , Tatsuya Tanaka 1 , Midori Shiozaki 1 , Koji Mizoguchi 1 , Yosuke Samoto 1 , Yoichi Matsuo 1 , Hiroki Takahashi 1 and Shuji Takiguchi 1 1 Nagoya City University Graduate School of Medicine, Department of Gastroenterological Surgery, Mizuho-ku, Nagoya 467-8601, Japan * These authors have contributed equally to this work Correspondence to: Hideyuki Ishiguro, email: h-ishi@med.nagoya-cu.ac.jp Keywords: colon cancer, β-catenin, NOTCH1, NICD1, prognosis Received: May 29, 2016 Accepted: June 27, 2017 Published: July 25, 2017 ABSTRACT Purpose and Methods: The translocation of β-catenin/CTNNB1 to the nucleus activates Wnt signaling and cell proliferation; however, the precise mechanism underlying this phenomenon remains unknown. Previous reports have provided evidence that NOTCH1 is involved in the Wnt signaling pathway. Therefore, we sought to determine the mechanism by which NOTCH1 influences the Wnt/β-catenin pathway. We constructed a vector expressing the NOTCH1 intracellular domain (NICD1) and transfected the vector into HCT116 which has low expression of NICD1. Furthermore, inhibition of NOTCH signal pathway in SW480 which has abundant NICD1 expression, was performed by transfection of siNICD1 or DAPT, gamma secretase inhibitor, treatment. In addition, we evaluated NICD1 and β-catenin localization in colon cancer cell lines and in 189 colon cancer tissue samples and analyzed the correlation between the nuclear localization of NICD1 and the clinicopathological features of colon cancer patients. Results: Immunohistochemical assays demonstrated that NICD1 and β-catenin exhibited a similar localization pattern in colon cancer tissues. In addition, we found that NICD1 induced the translocation of β-catenin to the nucleus and that NICD1 and β-catenin co-localized in the nucleus. Overexpression of NICD1 increased luciferase activity of Wnt signal pathway. On the other hand, reduction of NICD1 reduced luciferase activity of Wnt signaling pathway. In the 189 analyzed colon cancer cases, multivariate COX regression analysis demonstrated the independent prognostic impact of nuclear localization of NICD1(p=0.0376). Conclusion: NOTCH1 plays a key role in the Wnt pathway and activation of NOTCH1 is associated with the translocation of β-catenin to the nucleus.

Side-to-side anastomoses are more frequently performed. This method is relatively simple, timesaving, and can be applied in a variety of settings where anastomoses are necessary. Despite some advances, stapled anastomoses have inherent weak points. With any type of side-to-side anastomosis, the crotch is formed at the tip portion of the stapler; this crotch area is the weak point. We describe a novel surgical technique for side-to-side anastomosis using a reinforced crotch. After distal gastrectomy, a small incision was made on the greater curvature of the remnant stomach and the posterior side of the duodenum. We use a 60-mm linear stapler, namely, the Endo GIATM Reinforce Reload (Covidien Japan). Therefore, the stapler length inserted into the stomach and duodenum is 45 mm. The reinforce reloads have a preloaded reinforcement material on the both anvil and cartridge. One or two supporting sutures were added to the center of the common enterotomy. Pulling up on the two pieces of Neoveil® and the sutures, the common enterotomy was closed with a linear stapler. Delta-shaped anastomosis is then accomplished. We also use a reinforced reload in a side-to-side anastomosis between two segments of jejunum. Neoveil® is thin and soft; we found no problem using either a hand thrown suture or stapler to close the entry hole. In fact, we found that the excess Neoveil® is very useful. Neoveil® can be a substitute for the sutures. Only one or two hand thrown sutures were then necessary to close the common enterotomy. And we do not add the reinforce suture of the crotch at all. This novel method is a simple and useful method and can be used in side-to-side anastomoses in a variety of settings.

Rationale: Heart failure and atherosclerosis share the underlying mechanisms of chronic inflammation followed by fibrosis. A highly conserved microRNA (miR), miR-33, is considered as a potential therapeutic target for atherosclerosis because it regulates lipid metabolism and inflammation. However, the role of miR-33 in heart failure remains to be elucidated. Objective: To clarify the role of miR-33 involved in heart failure. Methods and Results: We first investigated the expression levels of miR-33a/b in human cardiac tissue samples with dilated cardiomyopathy. Increased expression of miR-33a was associated with improving hemodynamic parameters. To clarify the role of miR-33 in remodeling hearts, we investigated the responses to pressure overload by transverse aortic constriction in miR-33–deficient (knockout [KO]) mice. When mice were subjected to transverse aortic constriction, miR-33 expression levels were significantly upregulated in wild-type left ventricles. There was no difference in hypertrophic responses between wild-type and miR-33KO hearts, whereas cardiac fibrosis was ameliorated in miR-33KO hearts compared with wild-type hearts. Despite the ameliorated cardiac fibrosis, miR-33KO mice showed impaired systolic function after transverse aortic constriction. We also found that cardiac fibroblasts were mainly responsible for miR-33 expression in the heart. Deficiency of miR-33 impaired cardiac fibroblast proliferation, which was considered to be caused by altered lipid raft cholesterol content. Moreover, cardiac fibroblast–specific miR-33–deficient mice also showed decreased cardiac fibrosis induced by transverse aortic constriction as systemic miR-33KO mice. Conclusion: Our results demonstrate that miR-33 is involved in cardiac remodeling, and it preserves lipid raft cholesterol content in fibroblasts and maintains adaptive fibrotic responses in the remodeling heart.

Di-N-acetylchitobiase (Ctbs) degrades β-1,4 glycoside bonds of the chitobiose core of free asparagine-linked glycan. This study examined whether Ctbs degrades chitin-oligosaccharides to GlcNAc in mammals. We analyzed Ctbs mRNA and protein expression in mouse tissues and characterized enzymatic activity using recombinant mouse Ctbs expressed in Escherichia coli. Ctbs mRNA and protein were expressed in various tissues of mouse, including the stomach. Optimal conditions for recombinant Ctbs were pH 3.0 and 45°C, and the recombinant enzyme was retained more than 94% activity after incubation at pH 3.0–7.0 and below 37°C. The recombinant Ctbs hydrolyzed (GlcNAc)3 and (GlcNAc)6 at pH 3.0 and produced GlcNAc. The K m of Ctbs was lowest with (GlcNAc)3 as a substrate. k cat/K m was fourfold as high with (GlcNAc)3 and (GlcNAc)4 as substrates than with (GlcNAc)2. These results suggest that Ctbs digests chitin-oligosaccharides or (GlcNAc)2 of reducing-end residues of oligosaccharides and produces GlcNAc in mouse tissues. Di-N-acetylchitobiase (Ctbs) is most active at pH 3.0 and retained more than 94% activity after incubation at pH 3.0–7.0 and below 37°C. The preferred substrate of recombinant Ctbs is (GlcNAc)3.

Highlights • FACE is a simple, qualitative and quantitative method. • The standard curve warrants quantification of chitooligosaccharides of up to 10 nmol regardless on used buffer system. • Our improved FACE method enable us to quantify chitooligosaccharides produced by chitinases at pH 2.0–8.0. • Determination of the combinatory effects of the Chit1 and AMCase using the FACE method., Fluorophore-assisted carbohydrate electrophoresis (FACE) enables detection and quantification of degradation products from artificial and natural chitin substrates such as 4-NP-(GlcNAc)2, (GlcNAc)4 and colloidal chitin. The FACE method has been improved by our group for analysis of chitooligosaccharides in the presence of several buffer systems commonly used in the biochemical evaluation of chitinolytic activities of enzymes at pH 2.0–8.0. FACE is a very sensitive technique detecting picomolar amounts of molecules. We optimized the detection conditions as follows: exposure type, precision; sensitivity, high resolution; exposure time, 5 s. We evaluated the (GlcNAc)2 levels using a standard curve that allows chitooligosaccharides quantification at up to 10 nmol amounts. Using the method presented here, the chitinolytic properties of different chitinases can be compared directly. Serratia chitinase A (ChiA) and chitinase B (ChiB), two well-studied bacterial chitinases, have been shown by HPLC to have a synergistic effect on the chitin degradation rate. Using the FACE method, we determined the combinatory effects of mouse chitotriosidase (Chit1) and acidic mammalian chitinase (AMCase) in natural chitin substrates processing.•FACE is a simple and quantitative method.•Our improved procedure enables the quantification of chitooligosaccharides produced by chitinases at pH 2.0–8.0.•FACE is able to quantify chitooligosaccharides at up to 10 nmol amounts., Graphical abstract Image, graphical abstract

The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes-associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD-mediated gene expressions in VSMCs remains to be elucidated, then we sought to investigate a novel regulator of YAP/TEAD transactivation involved in vascular diseases. We first investigated novel YAP/TEAD regulators using lentiviral shRNA library in HEK 293T-based TEAD-responsive reporter cell line and detected Homeobox A4 (HOXA4) as a potent repressor of YAP/TEAD transcriptional activity. HOXA4 attenuated YAP/TEAD-mediated gene expression independently of YAP phosphorylation, and co-immunoprecipitation assays revealed that HOXA4 interacts with TEADs but not YAP. Mechanistically, HOXA4 attenuated YAP/TEAD-mediated transcription by competing with YAP for TEAD binding. We also clarified that the expression of HOXA4 is relatively abundant in the vasculature, especially in VSMCs. In vitro experiments in human VSMCs showed HOXA4 maintains the differentiation state of VSMCs via inhibition of YAP/TEAD-induced phenotypic switching characterized by cell morphology, cell proliferation, and gene expression patterns. We generated Hoxa4-decifient mice and confirmed the downregulation of smooth muscle-specific contractile genes and the exacerbation of vascular remodeling after carotid artery ligation in vivo. Our results demonstrate HOXA4 is a novel repressor of VSMC phenotypic switching by inhibiting YAP/TEAD-mediated transcription. These findings give us a better understanding of the vascular pathophysiology and a novel therapeutic approach for vascular remodeling.

Background Micro RNA (miR)‐33 targets cholesterol transporter ATP ‐binding cassette protein A1 and other antiatherogenic targets and contributes to atherogenic progression. Its inhibition or deletion is known to result in the amelioration of atherosclerosis in mice. However, mice lack the other member of the miR‐33 family, miR‐33b, which exists in humans and other large mammals. Thus, precise evaluation and comparison of the responsibilities of these 2 miRs during the progression of atherosclerosis has not been reported, although they are essential. Methods and Results In this study, we performed a comprehensive analysis of the difference between the function of miR‐33a and miR‐33b using genetically modified mice. We generated 4 strains with or without miR‐33a and miR‐33b. Comparison between mice with only miR‐33a (wild‐type mice) and mice with only miR‐33b (miR‐33a −/− /miR‐33b +/+ ) revealed the dominant expression of miR‐33b in the liver. To evaluate the whole body atherogenic potency of miR‐33a and miR‐33b, we developed apolipoprotein E–deficient/miR‐33a +/+ /miR‐33b −/− mice and apolipoprotein E–deficient/miR‐33a −/− /miR‐33b +/+ mice. With a high‐fat and high‐cholesterol diet, the apolipoprotein E–deficient/miR‐33a −/− /miR‐33b +/+ mice developed increased atherosclerotic plaque versus apolipoprotein E–deficient/miR‐33a +/+ /miR‐33b −/− mice, in line with the predominant expression of miR‐33b in the liver and worsened serum cholesterol profile. By contrast, a bone marrow transplantation study showed no significant difference, which was consistent with the relevant expression levels of miR‐33a and miR‐33b in bone marrow cells. Conclusions The miR‐33 family exhibits differences in distribution and regulation and particularly in the progression of atherosclerosis; miR‐33b would be more potent than miR‐33a.

With the widespread of the novel coronavirus (SARS-CoV-2), the inactivation of bacteria and viruses using ultraviolet (UV) light has been reevaluated. However, there are many applications where the safety to the human body itself and inactivation effect itself are questioned, and there is a movement to review the UV-C guidelines (Global Lighting Association, Position Statement on Germicidal UV-C Irradiation UV-C SAFETY GUIDELINES, 2020). Since the Minamata Convention on Mercurybans the production of mercury in principle, deep-ultraviolet light-emitting diodes (UVC-LEDs) are now being used in place of mercury lamps. In this paper, we will discuss effective irradiation methods for the inactivation of pathogens on solid surfaces, the inactivation of pathogens in water, and the inactivation of viruses in aerosols using UVC-LED.

Ultra-multiplex coherent anti-Stokes Raman scattering (CARS) spectroscopic imaging was used to visualize the distribution of water concentration in human skin ex vivo. The CARS signal of the OH stretching vibrational mode of water was found to coexist with the signal of intercellular lipids such as ceramides, which were visualized by a sharp vibrational band at 2882 cm−1. Depth-resolved CARS spectroscopic imaging of a skin sample revealed that ceramides were localized in the stratum corneum. These findings demonstrate the powerful potential of CARS spectroscopic imaging for probing pathological changes caused by anomalous water concentration distribution in human skin.

The regioselective bromine-lithium exchange reaction of 2,4-dibromo-1-(1-methoxy-1-methylethoxymethyl)benzene ( 2 ), which resulted in optimized selectivity of 220:1, is described. Applying this method to the synthesis of tofogliflozin ( 1 ) as a SGLT2 inhibitor is also described. Selective and sequential metalation-functionalization of 2 led to the synthesis of 1 in 47% overall yield.

Highlights • The indications for stripping of the esophagus have decreased due to the widespread of endoscopic mucosal resection and thoracoscopic surgery. • Even if indications for this procedure have decreased, this is an important option in the armamentarium of the esophageal surgeon., Introduction Patients with esophageal cancer frequently cannot tolerate thoracotomy due to their overall debilitated condition. Moreover, some patients have severe adhesions in the thoracic cavity. Eversion stripping of the esophagus is an option for resection in these patients. Presentation of case A 64-year-old man was admitted to our institution with the chief complaint of epigastric pain. Endoscopic examination showed a protruding lesion 22 cm from the incisors, with a superficial and circumferential mucosal irregularity on the distal side of the lesion. Biopsy revealed squamous cell carcinoma. Clinical stage was T1b(sm)N0M0, cStage I. In addition to the poor pulmonary status of the patient, adhesions in the intrathoracic cavity were predicted. The decision was made to perform esophageal resection without a thoracotomy. In order to ensure complete invagination of the esophagus, the esophagus was insufflated prior to stripping. The stripping process was observed with a gastroscope. During the stripping, the esophagus did not bunch up, and stripping was smooth and with minimal resistance. Discussion The stripping resection of the esophagus is an important option for the esophageal surgeon. In this case report, we describe a new eversion stripping method of the esophagus. This easy and reliable stripping method incorporates intraesophageal insufflation. Conclusion The indications for blunt esophageal dissection without thoracotomy have been decreasing. On the other hand, our method seems to be useful in optimal case of stripping of esophagus.

Acidic mammalian chitinase (AMCase) is implicated in asthma, allergic inflammation, and food processing. Little is known about genetic and evolutional regulation of chitinolytic activity of AMCase. Here, we relate human AMCase polymorphisms to the mouse AMCase, and show that the highly active variants encoded by nonsynonymous single-nucleotide polymorphisms (nsSNPs) are consistent with the mouse AMCase sequence. The chitinolytic activity of the recombinant human AMCase was significantly lower than that of the mouse counterpart. By creating mouse-human chimeric AMCase protein we found that the presence of the N-terminal region of human AMCase containing conserved active site residues reduced the enzymatic activity of the molecule. We were able to significantly increase the activity of human AMCase by amino acid substitutions encoded by nsSNPs (N45, D47, and R61) with those conserved in the mouse homologue (D45, N47, and M61). For abolition of the mouse AMCase activity, introduction of M61R mutation was sufficient. M61 is conserved in most of primates other than human and orangutan as well as in other mammals. Orangutan has I61 substitution, which also markedly reduced the activity of the mouse AMCase, indicating that the M61 is a crucial residue for the chitinolytic activity. Altogether, our data suggest that human AMCase has lost its chitinolytic activity by integration of nsSNPs during evolution and that the enzyme can be reactivated by introducing amino acids conserved in the mouse counterpart.

Recent studies have shown constitutive activation of the Notch signaling pathway in various types of malignancies. However, it remains unclear whether this signaling pathway is activated in gastric cancer. In the present study, the aim was to investigate the role of Notch signaling in gastric cancer by investigating the subcellular localization of Notch-associated proteins in tissue samples from gastric cancer patients. Samples were obtained from 115 gastric cancer patients who had undergone surgery at the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science without pre-operative chemotherapy or radiation. Subsequently the correlation between translocation of NOTCH1 intracellular cytoplasmic domain (NICD) into the nucleus (as measured by immunostaining) and survival in gastric cancer patients after surgery was investigated. The results were analyzed in reference to the patients' clinicopathological characteristics and the effects of these results on patient prognosis were determined. Significant correlations were observed between NICD nuclear localization and clinicopathological characteristics, such as tumor status (T factor), lymph node status (N factor), pathological stage and differentiation status. No significant correlations were observed between NICD nuclear localization and age, gender, tumor location, vein invasion or lymphatic invasion. Patients with >30% of cancer cell nuclei positively stained for NICD (as revealed by immunostaining) were associated with a significantly shorter survival following surgery than patients with

Patients with unresectable esophageal cancer suffer from dysphagia, causing severe malnutrition and reduced quality of life (QOL). We elect to perform bypass because patients can have greater long-term survival with chemoradiation following this operation. We sought to compare complications in cases of bypass without thoracotomy versus those with thoracotomy. Thirty-four locally advanced esophageal cancer patients between 2007 and 2014 were studied. Eighteen patients underwent thoracotomy, and 16 patients did not have a thoracotomy. CT was obtained to check the anastomosis and the oral stump of the esophagus and to measure the diameter of the intrathoracic esophagus. In the thoracotomy group, the rate of postoperative pulmonary complications was high. On the other hand, in the non-thoracotomy group, the rates of anastomotic leak and recurrent nerve paralysis were high. The stump of the esophagus was 2 cm lower in the T group than in the nT group. As the esophagus shortens after division, the final difference in esophageal height between the groups was only around 1 cm. We concluded that a viable gastric tube with a good blood supply as well as a careful cervical operation are the most important aspects of the esophageal bypass operation.

Connexin 43 (Cx43) is an important gap junction protein in vertebrates, which has been reported to function as a tumor suppressor in a number of organs. However, the mechanism underlying the effect of Cx43 on tumor progression remains unknown, with only a limited number of studies reporting on the role of Cx43 in esophageal cancer. In the present study, Cx43 expression was analyzed by immunohistochemical staining and the associations between Cx43 expression and clinicopathological characteristics or prognosis were evaluated. Cx43 was expressed at a high frequency in patients with esophageal squamous cell carcinoma (ESCC). Of the 98 ESCC cases investigated, positivity for Cx43 was observed in 62 cases (63.26%). In patients with high Cx43 expression, the survival rates were significantly reduced compared with those in patients with low Cx43 expression. Moreover, the overexpression of Cx43, as measured by immunohistochemistry, was an independent prognostic indicator of ESCC. Thus, our data indicated that Cx43 may be a candidate molecular prognostic marker and molecular target for the development of an effective therapeutic intervention for patients with esophageal cancer.

Background Few studies have been designed regarding optimal reinforcement of the crotch of a side-to-side anastomosis. The purpose of this study was to clarify the weak point of the side-to-side anastomosis and to evaluate the effect of bioabsorbable reinforcement material. Methods Fresh pig small bowel was used for all experiments. A side-to-side anastomosis was performed using a linear stapler, and the burst pressure of the anastomosis was measured. Three separate experiments were done. In experiment 1, the weak point and the burst pressure of that point were defined. In experiment 2, the burst pressure of the side of the anastomosis was measured. In experiment 3, we evaluated the effect of Neoveil® to strengthen the weak point of the anastomosis. Results The weak point of the side-to side anastomosis was the crotch and the burst pressure was 39.8 ± 5.7 mmHg. The burst pressure of the side of the anastomosis was 109.9 ± 7.9 mmHg. This was significantly higher than the burst pressure of the crotch (P = 0.008). The burst pressure of the crotch in the group with Neoveil® was 83.3 ± 14.9 mmHg. This pressure was significantly higher than the group with no Neoveil® reinforcement (P = 0.001). Conclusion These findings suggest that the use of Neoveil® as a buttressing material is associated with reinforced staple lines and increased crotch burst pressures compared to non-buttressed staple lines. Neoveil® was found to perform comparably to clinically available buttress materials in this ex vivo model. Reinforcement of the weak point of the side-to-side anastomosis with Neoveil®may lead to fewer anastomotic leaks., Highlights • The purpose of this study was to clarify the weak point of the side-to-side anastomosis and to evaluate the effect of Neoveil®. • The use of Neoveil® is associated with reinforced staple lines and increased crotch burst pressures compared to non-buttressed staple lines. • Neoveil® was found to perform comparably with clinically available buttress materials in this ex vivo model.

Introduction Various types of staplers are used for gastric tube formation after esophagectomy. Using a stapling device, a gastric tube can safely be created in a short amount of time. The problems with gastric tube creation using only linear type staplers include staple overlap as well as the problem of cost associated with using multiple staplers. To address this, both linear and radial type staplers have been introduced. We herein compare three methods of gastric tube creation. Methods From 2012 to 2014, 62 patients with esophageal cancer underwent esophagectomy with gastric tube reconstruction. We evaluated and compared the mean number of stapler loads and cost in each groups. Results The mean number of stapler loads was 6.24 in method A, 5.16 in method B, and 4.33 in method C. The mean cost accounting for total staple fires per case was 3116.07 dollars in the method A group, 2576.74 dollars in the method B group, and 2447.78 dollars in the method C group. Anastomotic leaks developed in 4 cases in the method A group and in 3 cases in the method B group. There were no anastomotic leaks in the method C group. Conclusion We hypothesize that by using radial type staplers, we can create a durable gastric tube and reduce the number of staplers and therefore reduce operative cost., Highlights • We herein compare three methods of gastric tube creation. • Using radial type staplers, we can create a durable gastric tube. • We also reduce the number of staplers and therefore reduce operative cost.

[Objective] To determine whether three sputum examinations with fluorescent staining are necessary to diag- nose tuberculosis (TB) in our hospital. [Patients] From April 2005 to December 2012, 379 TB patients were admitted and received anti-TB therapy in our hospital. [Methods] A retrospective study was conducted to assess the positivity rates of sputum smears based on three exami- nations. The positivity rate of first sputum smear and the cumulative smear-positive rates in the second and third were determined. Then, we also determined difference of positivity rates in sputum properties, sampling procedures and cavity formation. [Results] Of the 379 patients who met the screening criteria, 300 tested positive based on the first sputum smear (79.2%). The positivity rate of the first sputum smears was higher in the purulent sputum group than in the mucous sputum group (91.2% vs. 72.3%). Cavity formation, and sputum extraction procedures were not related to the positivity rate of the first sputum smears. In the mucous sputum group, the cumulative smear-positive rate in the second test significantly rose, but did not rise in the third test. [Conclusions] Three sputum smear examinations were necessary in patients who submitted mucous sputum samples. It is important to get purulent sputum.

Acute cardiac rupture and adverse left ventricular (LV) remodeling causing heart failure are serious complications of acute myocardial infarction (MI). While cardio-hepatic interactions have been recognized, their role in MI remains unknown. We treated cultured cardiomyocytes with conditioned media from various cell types and analyzed the media by mass spectrometry to identify α1-microglobulin (AM) as an Akt-activating hepatokine. In mouse MI model, AM protein transiently distributed in the infarct and border zones during the acute phase, reflecting infiltration of AM-bound macrophages. AM stimulation activated Akt, NFκB, and ERK signaling and enhanced inflammation as well as macrophage migration and polarization, while inhibited fibrogenesis-related mRNA expression in cultured macrophages and cardiac fibroblasts. Intramyocardial AM administration exacerbated macrophage infiltration, inflammation, and matrix metalloproteinase 9 mRNA expression in the infarct and border zones, whereas disturbed fibrotic repair, then provoked acute cardiac rupture in MI. Shotgun proteomics and lipid pull-down analysis found that AM partly binds to phosphatidic acid (PA) for its signaling and function. Furthermore, systemic delivery of a selective inhibitor of diacylglycerol kinase α-mediated PA synthesis notably reduced macrophage infiltration, inflammation, matrix metalloproteinase activity, and adverse LV remodeling in MI. Therefore, targeting AM signaling could be a novel pharmacological option to mitigate adverse LV remodeling in MI.

The problem of efficiently identifying critical nodes that substantially degrade network performance if they do not function is crucial and essential in analyzing a large complex network such as social networks on the Web, and it is still challenging. In this paper, we tackle this problem under a realistic situation where each link is probabilistically disconnected reflecting that an information path between two persons in a social network is not always open to pass on a message, rather than assuming that every information path is always open and passes on any information from one to the other. To solve this problem, we focus on the articulation point and utilize the bridge detection technique in graph theory to efficiently identify critical nodes in case the node reachability is taken as the performance measure. This corresponds to the total number of people who can receive information issued by every single person in a social network. Using two real-world social networks, we empirically show that the proposed method has a good scalability with respect to the network size and the nodes our method identified possesses unique properties and they are difficult to be identified by using conventional centrality measures.

MicroRNA 33 (miR-33) targets ATP-binding cassette transporter A1 (ABCA1), and its deficiency increases serum high-density lipoprotein (HDL)-cholesterol (HDL-C) and ameliorates atherosclerosis. Although we previously reported that miR-33 deficiency increased peripheral Ly6Chigh monocytes on an ApoE-deficient background, the effect of miR-33 on the monocyte population has not been fully elucidated, especially in a wild-type (WT) background. We found that Ly6Chigh monocytes in miR-33−/− mice were decreased in peripheral blood and increased in bone marrow (BM). Expansion of myeloid progenitors and decreased apoptosis in Lin− Sca1+ c-Kit+ (LSK) cells were observed in miR-33−/− mice. A BM transplantation study and competitive repopulation assay revealed that hematopoietic miR-33 deficiency caused myeloid expansion and increased peripheral Ly6Chigh monocytes and that nonhematopoietic miR-33 deficiency caused reduced peripheral Ly6Chigh monocytes. Expression of high-mobility group AT-hook 2 (HMGA2) targeted by miR-33 increased in miR-33-deficient LSK cells, and its knockdown abolished the reduction of apoptosis. Transduction of human apolipoprotein A1 and ABCA1 in WT mouse liver increased HDL-C and reduced peripheral Ly6Chigh monocytes. These data indicate that miR-33 deficiency affects distribution of inflammatory monocytes through dual pathways. One pathway involves the enhancement of Hmga2 expression in hematopoietic stem cells to increase Ly6Chigh monocytes, and the other involves the elevation of HDL-C to decrease peripheral Ly6Chigh monocytes.

Background: In gastrointestinal surgery, the quality of anastomosis is one of the most important factors influencing the postoperative course. The purpose of this study was to verify the effectiveness and the mechanism of one type of reinforcement material. Methods: We analyzed the effect of Neoveil on the rate of staple line failure. Fresh pig small bowel was used. Neoveil sheets were placed on the anvil alone, cartridge alone or both sides of the stapler. Groups were: A, without Neoveil; B, the cartridge and anvil; C, the cartridge alone; D, the anvil alone. The burst pressures were measured. Results: In group A, a leak occurred at the intestinal stump in 5 of 10 cases (As). In the other 5 cases, the mesenteric side burst before failure of the staple line (Am). In groups B, C, and D, the mesenteric side burst before failure of the staple line. The median leak pressure was 100±46 mm Hg in group A (As; 57±6, Am; 143±12). In the other groups, the leak pressures were approximately Original Research Article 140 mm Hg. In group As, the middle staple only exists on the edge of stump. In group Am, however, both sides of the 3-row staple line exist on the edge of stump. Conclusion: The burst pressure of the stump became the result of the bipo of the stump staple line is affected by the arrangement of the staples. Neoveil obtaining a stronger staple line.

Platypnea-orthodeoxia syndrome (POS) is a rare condition characterized by interatrial right-to-left shunting that is exacerbated in the upright position. We herein report a 78-year-old woman with POS that remained undiagnosed for 2 years, despite repetitive transthoracic echocardiography (TTE). POS was ultimately diagnosed using contrast transesophageal echocardiography (TEE), which revealed a marked increase in right-to-left shunting in the sitting position, associated with simultaneous desaturation. Therefore, we propose that POS should be considered according to the clinical symptoms, regardless of the repetitive TTE results, and contrast TEE should be performed in both the supine and sitting positions to exclude a diagnosis of POS.

Reverse osmosis (RO) technology has been widely applied to water treatment such as seawater desalination, and lots of large plants with RO are in operation in the world. However, global water problems are still getting more serious, and much larger plants will be required to secure sufficient water resource in the near future. Mega-ton Water System project was carried out with the aim of developing key 21st century water treatment technologies for sustainable management of water environment and for low-carbon path. Low pressure RO membrane for seawater desalination has been studied in the project as a part of the core technologies to realize mega plant which is capable of producing 1,000,000 m3 of freshwater per day. Fundamental and scientific research for RO membranes based on fine structure analyses by means of transmission electron microscopy with a special technique for sample preparation was conducted, and practical tools for designing new innovative RO membrane were acquired by the structure analyses to quantify the physicochemical and chemical properties of RO membranes. As the result of studying on structural design of RO membrane, low pressure SWRO membrane which enables to reduce energy consumption compared to conventional ones in the past of SWRO was obtained.

Mouse acidic mammalian chitinase (AMCase) plays important physiological roles in defense and nutrition. AMCase is composed of an N-terminal catalytic domain (CatD) and a C-terminal chitin-binding domain (CBD). We expressed CatD of mouse AMCase as a recombinant fusion protein with Protein A and V5-His in Escherichia coli (Protein A-CatD-V5-His), evaluated its functional properties and compared them to the full-length AMCase (Protein A-AMCase-V5-His). Under our experimental conditions, the chitinolytic activity of both proteins against 4-nitrophenyl N,N'-diacetyl-β-d-chitobioside was equivalent with regard to their specific enzymatic activities, optimal pH and temperature as well as to the pH and temperature stability. CatD bound to chitin beads and cleaved the N-acetylglucosamine hexamer, colloidal and crystalline chitin as well as the shrimp shell, and released primarily N,N'-diacetylchitobiose fragments at pH 2.0. These results indicate that the primary structure of CatD is sufficient to form a proper tertiary structure required for chitinolytic activity, recognize chitin substrates and degrade them in the absence of a CBD. Our recombinant proteins can be used for further studies evaluating pathophysiological roles of AMCase in different diseases.

Highlights • Twelve patients who underwent esophageal bypass between 2006 and 2011 in our hospital were studied. • Ten patients were able to enjoy oral intake up until the last few days of life. Three patients survived for more than 10 months. • The only complication was postoperative delirium in 1 patient., Introduction When esophageal cancer infiltrates the respiratory tract and forms a fistula, a patient’s quality of life falls remarkably. Abstinence from oral feeding is necessary to prevent respiratory complications including pneumonia. Surgery is sometimes necessary to maintain quality of life. The aim of this study was to examine clinical outcomes of esophageal cancer complicated by tracheobronchial fistula. Presentation of case Twelve patients who underwent esophageal bypass between 2006 and 2011 in our hospital were studied. Patient characteristics, therapeutic course, outcome, and operation type were compared. Six patients among 8 who could not tolerate oral feeding could do so after bypass surgery. Ten patients were able to enjoy oral intake up until the last few days of life. Three patients survived for more than 10 months. In spite of undergoing an operation, 1 patient survived for only 2 months and another for 4 months. The only complication was postoperative delirium in 1 patient. Discussion While surgical bypass is more invasive than procedures such as endoscopic stenting, we had few complications after operative intervention and were able to maintain quality of life in our patients. Conclusion This bypass procedure is a treatment option for patients with tracheobronchial fistula from advanced esophageal cancer.

Background: Few studies have been conducted regarding the optimal staple direction in gastrointestinal anastomosis. The purpose of this study was to evaluate the burst pressure of the anastomosis depending on the firing direction of the stapler. Methods: Pig esophagus and small bowel were used for all experiments. The small intestine represented a thin intestinal tract and the esophagus represented a thick intestinal tract. A side-to-side anastomosis was performed using a linear stapler, and the burst pressure was measured. A leak test on the anastomosis was then performed and burst pressures measured. Results: Burst pressures after anastomosis using a GIA™ 100-3.8 were 47.4 ± 10.4 mm Hg. With the same GIA, the burst pressure was significantly greater when the staples were driven from the small intestine into the esophagus (83.3 ± 17.3 mm Hg). Using the GIA™ 100-4.8, it was found that the burst pressure was significantly greater when the staplers were driven into the small intestine versus the esophagus (51.6 ± 7.1 vs. 68.6 ± 16.1 mm Hg). There was no significant difference between the different GIAs when fired in the same direction. Conclusion: Burst pressures were significantly greater when the staplers were driven from the small intestine into the esophagus. The direction of the staple line influences the strength of the anastomosis.

Bronchiectasis (BE), a syndrome that presents with persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi, has not been well-characterized in Asians. This study aims to review the etiology, causal pathogens, imaging patterns, and treatment of BE and to define the prognostic factors for acute exacerbation in a Japanese population.We performed a retrospective cohort study of 147 patients (104 women; median age, 73 years; range, 30-95 years) with BE at our institution using high-resolution computed tomography to identify imaging patterns and the area of pulmonary involvement.Common BE etiologies were idiopathic (N=50 [34%]), sinobronchial syndrome (N=37 [25%]), non-tuberculous mycobacteriosis (NTM; N=26 [18%]), and previous respiratory infection (N=21[14%]). Pseudomonas aeruginosa was the most common causal pathogen (24%). Common imaging patterns were cylindrical (66%) and mixed including cylindrical pattern (47%). The median number of involved lobes was 2; 49% of the patients had ≥ 3 involved lobes, and 49% had middle lobe and left lingula dominant BE. Patients with predominantly lower lobe BE comprised 4% of the NTM group and 48% of the non-NTM group (P0.001). In multivariate analysis, cystic BE was a predictor for frequent exacerbations in non-NTM patients (OR=7.947; P=0.004) which led to increased hospital admissions (OR=4.691; P=0.004).Idiopathic and sinobronchial syndrome were common causes of BE. Etiology did not contribute to imaging pattern or predictors of exacerbations. Cystic BE was a predictor for frequent exacerbations in the non-NTM BE patients.

Recently, it has been reported that spontaneous left ventricular wall thickening occurs among patients with takotsubo syndrome, which affects the long-term prognosis of such patients due to cerebral and cardiac complications. We herein report two cases of transient left ventricular wall thickening with takotsubo syndrome in which sequential cardiac magnetic resonance imaging revealed the existence of edematous changes in the thickened wall. Notably, a left ventricular aneurysm was detected during the course of ventricular wall thickening and may have played a role in the development of serious complications accompanied by takotsubo syndrome. This is the first case report of left ventricular aneurysm occurring with ventricular wall thickening due to takotsubo syndrome.

Two archaeal trehalase-like genes, Saci1250 and Saci1816, belonging to glycoside hydrolase family 15 (GH15) from the acidophilic Crenarchaeon Sulfolobus acidocaldarius were expressed in Escherichia coli. The gene products showed trehalose-hydrolyzing activities, and the names SaTreH1 and SaTreH2 were assigned to Saci1816 and Saci1250 gene products, respectively. These newly identified enzymes functioned within a narrow range of acidic pH values at elevated temperatures, which is similar to the behavior of Euryarchaeota Thermoplasma trehalases. SaTreH1 displayed high KM and kcat values, whereas SaTreH2 had lower KM and kcat values despite a high degree of identity in their primary structures. A mutation analysis indicated that two glutamic acid residues in SaTreH1, E374 and E574, may be involved in trehalase catalysis because SaTreH1 E374Q and E574Q showed greatly reduced trehalose-hydrolyzing activities. Additional mutations substituting G573 and H575 residues with serine and glutamic acid residues, respectively, to mimic the TVN1315 sequence resulted in a decrease in trehalase activity and thermal stability. Taken together, the results indicated that Crenarchaea trehalases adopt active site structures that are similar to Euryarchaeota enzymes but have distinct molecular features. The identification of these trehalases could extend our understanding of the relationships between the structure and function of GH15 trehalases as well as other family enzymes and will provide insights into archaeal trehalose metabolism.

Social Media allows people to post widely and share the posted online-items. Such items gain their popularity by the amount of attention received. Thus, studies on modeling the arrival process of attention to an individual item have recently attracted a great deal of interest. In this paper, we propose, by combining a Dirichlet process with a Hawkes process in a novel way, a probabilistic model, called cooperative Hawkes process (CHP) model, to discover the cooperative structure among all the items involved. The proposed model takes into account all the arrival processes of shares for those items. We develop an efficient method of inferring the CHP model from the observed sequences of share events, and present an effective framework for predicting the future popularity of each of these items. Using synthetic data and real data from a cooking-recipe sharing site, we demonstrate the effectiveness of the CHP model, and uncover the cooperative structure among cooking-recipes in view of attention dynamics.

Group centrality is an extension of the conventional node centrality in which the importance of a group of nodes together is the target for performance evaluation. We used this notion and formulated a link creation problem to a spatial network. The kind of problem we want to solve is to find the best places to construct k new roads to maximize the evacuation performance. The problem is formulated as an optimization problem to maximize the gain of the group closeness centrality by creating a set of new roads (k links) with the constraints on the road range distance (link length limit Δ). The problem is NP-hard. We show that this problem is reduced to a node selection problem and the objective function is submodular when there is no constraint on the link length limit. We devised an efficient greedy algorithm to search for the best k new roads under the constraint of Δ that comprises three steps: centrality calculation, parents selection and nodes selection. We applied this algorithm to three real road networks of different cities and evaluated its performance with respect to k and Δ. The algorithm is quite efficient and obtains the efficiency gain of 10^3 to 10^6 compared with a naive method in which every single node is blindly tested as a candidate from which to create a new road.

Co-aggregation plays an important role in processing protein-rich food materials under heterogeneous conditions. The main cause of co-aggregation is an electrostatic attraction between oppositely charged molecules. This study investigated thermal aggregation of β-lactoglobulin (BLG) (pI = 5.1) and lysozyme (LYZ) (pI = 10.7) as a model for the heterogeneous conditions of a protein solution. BLG and LYZ were more aggregated in the mixture than in the single solutions. Co-aggregation of the BLG–LYZ mixture was not observed below 60 °C at which temperature BLG and LYZ retained their native structures. Adding sugars, salts, or amino acids to the BLG–LYZ mixture during the heat treatment revealed the co-aggregation process as follows. (i) All additives tested suppressed both the nucleation and growth of aggregates. (ii) Salts affected nucleation stage to the same degree, except arginine hydrochloride (Arg). (iii) Arg specifically suppressed both nucleation and growth of aggregates. These results indicate that co-aggregation in a protein mixture is more sensitive to the partial unfolding of proteins than that in a single protein solution, due to the presence of electrostatic attraction between different molecules. These results provide new insight into protein aggregation as well as the molecular mechanism of additives under heterogeneous conditions.

A 31-year-old woman developed a constant cough during the 8th week of pregnancy and was diagnosed with bronchial asthma. She was prescribed prednisolone and inhaled corticosteroids. At 28 weeks of pregnancy, she showed worsening weight loss, fever, night sweats, hoarseness, and coughs. At 31 weeks of pregnancy, a scatter shadow and cavitary lesions were detected on the chest radiograph. Acid- fast bacilli smear test and tuberculosis (TB) polymerase chain reaction tests yielded positive results (G-8), and she was diagnosed with TB. Contact tracing and screening indicated 3 patients with TB onset and 18 patients with latent TB infec- tion attributed to the initial patient, who infected a total of 36 people. In the present case, physicians were reluctant to order a chest radiograph for fear of harming the fetus and did not order sputum or interferon gamma release (IGRA) assay tests either. The diagnosis was delayed by 152 days, which was considered as a factor that caused the outbreak. The diag- nosis of TB in a pregnant patient may be very challenging because symptoms may initially be ascribed to the pregnan- cy, and delayed diagnosis and treatment of military TB can lead to the death of the mother and fetus. Consequently, to ensure early diagnosis and treatment, chest radiography and sputum and IGRA tests are recommended for pregnant women who have TB symptoms or are at high risk for TB.

Reverse osmosis membranes based on aromatic polyamide (ar-PA) are widely used in desalination of seawater, yet the microscopic mechanism of water diffusion through a polyamide layer remains elusive. Here, we study the structure and dynamics of polymer chains and water molecules in ar-PA in comparison to nylon 6 (one of aliphatic polyamides) under various water contents (0.0–15.9 wt%). The infrared (IR) difference spectrum between dry and moist ar-PA shows little change in amide A bands, in contrast to that of nylon 6 which yields a prominent dip. Theoretical analyses using molecular dynamics simulations and quantum electronic and vibrational calculations reveal that the dip in nylon 6 is caused by breaking of hydrogen bonds (HBs) among amide groups. The incoming water molecules that break amide-amide HBs are bound to polyamide chains nearby and diffuse slowly. On the other hand, the amide-amide HBs of ar-PA are kept upon hydration. Such polymer structure facilitates growth of large water clusters with more than 100 water molecules and rapid diffusion of water molecules. The amide A band serves as a fingerprint to characterize the water permeability of polyamide materials.