Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation.

During macroautophagy, cytoplasmic constituents are engulfed by autophagosomes. Lysosomes fuse with closed autophagosomes but not with unclosed intermediate structures. This is achieved in part by the late recruitment of the autophagosomal SNARE syntaxin 17 (STX17) to mature autophagosomes. However, how STX17 recognizes autophagosome maturation is not known. Here, we show that this temporally regulated recruitment of STX17 depends on the positively charged C-terminal region of STX17. Consistent with this finding, mature autophagosomes are more negatively charged compared with unclosed intermediate structures. This electrostatic maturation of autophagosomes is likely driven by the accumulation of phosphatidylinositol 4-phosphate (PI4P) in the autophagosomal membrane. Accordingly, dephosphorylation of autophagosomal PI4P prevents the association of STX17 to autophagosomes. Furthermore, molecular dynamics simulations support PI4P-dependent membrane insertion of the transmembrane helices of STX17. Based on these findings, we propose a model in which STX17 recruitment to mature autophagosomes is temporally regulated by a PI4P-driven change in the surface charge of autophagosomes.

Experimental determination and mathematical modeling of standard shapes of forming autophagosomes.

The formation of autophagosomes involves dynamic morphological changes of a phagophore from a flat membrane cisterna into a cup-shaped intermediate and a spherical autophagosome. However, the physical mechanism behind these morphological changes remains elusive. Here, we determine the average shapes of phagophores by statistically investigating three-dimensional electron micrographs of more than 100 phagophores. The results show that the cup-shaped structures adopt a characteristic morphology; they are longitudinally elongated, and the rim is catenoidal with an outwardly recurved shape. To understand these characteristic shapes, we establish a theoretical model of the shape of entire phagophores. The model quantitatively reproduces the average morphology and reveals that the characteristic shape of phagophores is primarily determined by the relative size of the open rim to the total surface area. These results suggest that the seemingly complex morphological changes during autophagosome formation follow a stable path determined by elastic bending energy minimization.

Natural history of asymptomatic gallbladder stones in clinic without beds: A long-term prognosis over 10 years.

BACKGROUND: Several studies have explored the long-term prognosis of patients with asymptomatic gallbladder stones. These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases. AIM: To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities. METHODS: We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022. When symptoms developed, patients were transferred to hospitals where appropriate treatment was possible. We investigated the asymptomatic and survival periods during the follow-up. RESULTS: Among the 237 patients, 214 (90.3%) remained asymptomatic, with a mean asymptomatic period of 3898.9279 ± 46.871 d (50-4111 d, 10.7 years on average). Biliary complications developed in 23 patients (9.7%), with a mean survival period of 4010.0285 ± 31.2788 d (53-4112 d, 10.9 years on average). No patient died of biliary complications. CONCLUSION: The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable. When the condition became symptomatic, the patients were transferred to hospitals with beds that could address it; thus, no deaths related to biliary complications were reported. This finding suggests that follow-up care in clinics without beds is possible.

α-Pyrrolidinononanophenone derivatives induce differentiated SH-SY5Y neuroblastoma cell apoptosis via reduction of antioxidant capacity: Involvement of NO depletion and inactivation of Nrf2/HO1 signaling pathway.

α-Pyrrolidinononanophenone (α-PNP) derivatives are known to be one of the hazardous new psychoactive substances due to the most extended hydrocarbon chains of any pyrrolidinophenones on the illicit drug market. Our previous report showed that 4'-iodo-α-PNP (I-α-PNP) is the most potent cytotoxic compound among α-PNP derivatives and induces apoptosis due to mitochondrial dysfunction and suppression of nitric oxide (NO) production in differentiated human neuronal SH-SY5Y cells. In this study, to clarify the detailed action mechanisms by I-α-PNP, we investigated the mechanism of reactive oxygen species (ROS) -dependent apoptosis by I-α-PNP in differentiated SH-SY5Y with a focus on the antioxidant activities. Treatment with I-α-PNP elicits overproduction of ROS such as H2O2, hydroxyl radical, and 4-hydroxy-2-nonenal, and pretreatment with antioxidant N-acetyl-L-cysteine is attenuated the SH-SY5Y cells apoptosis by I-α-PNP. These results suggested that the overproduction of ROS is related to SH-SY5Y cell apoptosis by I-α-PNP. In addition, I-α-PNP markedly decreased antioxidant capacity in differentiated cells than in undifferentiated cells and inhibited the upregulation of hemeoxygenase 1 (HO1) and glutathione peroxidase 4 (GPX4) expression caused by induction of differentiation. Furthermore, the treatment with I-α-PNP increased the nuclear expression level of BTB Domain And CNC Homolog 1 (Bach1), a transcriptional repressor of Nrf2, only in differentiated cells, suggesting that the marked decrease in antioxidant capacity in differentiated cells was due to suppression of Nrf2/HO1 signaling by Bach1. Additionally, pretreatment with an NO donor suppresses the I-α-PNP-evoked ROS overproduction, HO1 down-regulation, increased nuclear Bach1 expression and reduced antioxidant activity in the differentiated cells. These findings suggest that the ROS-dependent apoptosis by I-α-PNP in differentiated cells is attributed to the inactivation of the Nrf2/HO1 signaling pathway triggered by NO depletion.

Pyrolysis and steam gasification properties of mangroves.

The rising atmospheric CO2 emissions from the burning of fossil fuels remains a global concern. Mangrove forests, which are important for global biodiversity, are known for their high carbon fixation capacity. However, the characteristics of the pyrolysis and gasification of mangroves remain unclear. Thus, this study focused on mangroves' basic pyrolysis and steam gasification properties for use as a gasification fuel. Three mangrove species: Rhizophora mucronata, Bruguiera cylindrica, and Avicennia marina, were used as experimental samples. In addition, three species of land wood were used for comparison: Eucalyptus, Japanese cedar, and Japanese cypress. In addition to the raw sample, a demineralized sample was used for each sample to account for the influence of the alkali and alkaline earth metals (AAEMs) on pyrolysis and steam gasification. Thermogravimetric analysis was performed to obtain thermogravimetric curves of mangroves and land wood. A laboratory-scale instrument for pyrolysis and gasification using a batch-type horizontal electric furnace was also used at 800 °C in an inert and steam atmosphere. The char yield of raw mangroves was high and independent of the Klason lignin content, suggesting that AAEMs influence char formation during the initial pyrolysis of the mangroves. The results of pyrolysis and gasification under steam atmosphere showed that the H2 production ratio (Steam/Inert) from mangroves was 2.52-5.33, compared to 1.76-2.35 for land woods, the addition of steam significantly enhanced the steam gasification of mangroves. Mangroves contain relatively large amounts of AAEMs, which indicates their potential as a gasification feedstock.

A mechanism that ensures non-selective cytoplasm degradation by autophagy.

In autophagy, a membrane cisterna called the isolation membrane expands, bends, becomes spherical, and closes to sequester cytoplasmic constituents into the resulting double-membrane vesicle autophagosome for lysosomal/vacuolar degradation. Here, we discover a mechanism that allows the isolation membrane to expand with a large opening to ensure non-selective cytoplasm sequestration within the autophagosome. A sorting nexin complex that localizes to the opening edge of the isolation membrane plays a critical role in this process. Without the complex, the isolation membrane expands with a small opening that prevents the entry of particles larger than about 25 nm, including ribosomes and proteasomes, although autophagosomes of nearly normal size eventually form. This study sheds light on membrane morphogenesis during autophagosome formation and selectivity in autophagic degradation.

An Investigation of the Non-selective Etching of Synthetic Polymers by Electrospray Droplet Impact/Secondary Ion Mass Spectrometry (EDI/SIMS).

Among the various types of cluster secondary ion mass spectrometry (SIMS), electrospray droplet impact/secondary ion mass spectrometry (EDI/SIMS) is unique due to its high ionization efficiency and non-selective atomic/molecular-level surface etching ability. In this study, EDI/SIMS was applied to the non-selective etching of synthetic polymers of polystyrene (PS) and poly(9,9-di-n-octylfluonyl-2,7diyl) (PFO) deposited on a silicon substrate. The polymers gave characteristic fragment ions and the mass spectra remained unchanged with prolonged EDI irradiation time, indicating that non-selective etching can be achieved by EDI irradiation, a finding that is consistent with our previous reports based on EDI/X-ray photoelectron spectroscopy analyses. From the irradiation time and film thickness, the etching rates for PS and PFO were roughly estimated to be 0.6 nm/min and 0.15 nm/min, respectively, under the experimental conditions that were used. After the depletion of polymer sample on the surface, ion signals originating from the exposed silicon substrate were observed. This indicates that EDI/SIMS is applicable to the analysis of the interface of multilayered films composed of organic and inorganic materials.

Identity of the numerous bloodstains at the murder scene: molecular identification of fly artifacts and fly species by CO1 analysis.

Crime scenes may contain insect artifacts as well as samples of human origin. While the presence of insects can be important evidence in forensic medicine and forensic entomology, the insect artifacts sometimes interfere with the interpretation of bloodstain pattern analysis (BPA) which can be critical for accurate crime reconstruction. Fly artifacts are especially complicated to distinguish from true bloodstains. Indeed, we encountered a murder scene with numerous bloodstains inconsistent with the cause of death and had trouble interpreting them. The morphological method has been developed to distinguish them, but this method has to rely on the analyst's experience and opinion. This study aims not only to distinguish fly artifacts from true bloodstains but also to identify fly species by detecting fly DNA in small amounts of bloodstains at the scenes. Melt curve analysis of real-time PCR (qPCR) targeting cytochrome c oxidase subunit 1 (CO1) of mitochondrial DNA (mtDNA) was able to detect fly DNA in bloodstains from a murder scene. The fly DNA was sequenced from the qPCR product, and the fly species were identified by BLAST search. Fluorescence-labeled specific primers for four species of necrophagous flies were designed based on the sequences of the CO1 region, and differences in the length of the amplification products were used to identify fly species from trace amounts of fly DNA in the artifacts.

"Salvage techniques" are the key to overcome difficult biliary cannulation in endoscopic retrograde cholangiopancreatography.

Although the efficacy and safety of salvage techniques for biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) have been reported, few reports analyzed the choice of techniques and their clinical outcomes in large cohorts. This study aimed to evaluate the outcomes of biliary cannulation in patients with native papillae. We retrospectively identified 1021 patients who underwent initial ERCP from January 2013 to March 2020. We investigated background factors, treatment details, cannulation success rates, and adverse event rates. Then we analyzed a series of treatment processes, including salvage techniques such as double guidewire technique (DGT), needle knife pre-cutting (NKP), and transpancreatic pre-cut papillotomy (TPPP). The initial ERCP success rate using standard technique alone was 62.8%, which increased to 94.3% including salvage techniques. Salvage techniques were frequently required in patients with long oral protrusions (OR 2.38; 95% CI 1.80-3.15; p < 0.001). A total of 503 cases (49.3%) had long oral protrusions, 47.5% of which required the salvage techniques, much higher than 27.5% of not-long cases. Patients with long oral protrusions had a higher frequency of NKP. In conclusion, patients with long oral protrusions frequently required salvage techniques. Salvage techniques may help to overcome many difficult biliary cannulation cases.

K-point longitudinal acoustic phonons are responsible for ultrafast intervalley scattering in monolayer MoSe2.

In transition metal dichalcogenides, valley depolarization through intervalley carrier scattering by zone-edge phonons is often unavoidable. Although valley depolarization processes related to various acoustic phonons have been suggested, their optical verification is still vague due to nearly degenerate phonon frequencies on acoustic phonon branches at zone-edge momentums. Here we report an unambiguous phonon momentum determination of the longitudinal acoustic (LA) phonons at the K point, which are responsible for the ultrafast valley depolarization in monolayer MoSe2. Using sub-10-fs-resolution pump-probe spectroscopy, we observed coherent phonons signals at both even and odd-orders of zone-edge LA mode involved in intervalley carrier scattering process. Our phonon-symmetry analysis and first-principles calculations reveal that only the LA phonon at the K point, as opposed to the M point, can produce experimental odd-order LA phonon signals from its nonlinear optical modulation. This work will provide momentum-resolved descriptions of phonon-carrier intervalley scattering processes in valleytronic materials.

4'-Iodo-α-Pyrrolidinononanophenone Provokes Differentiated SH-SY5Y Cell Apoptosis Through Downregulating Nitric Oxide Production and Bcl-2 Expression.

Abuse of pyrrolidinophenone derivatives (PPs) is known to cause severe damage to the central nervous system due to their high lipophilicity. In this study, we compared sensitivity to toxicity elicited by 4'-iodo-α-pyrrolidinononanophenone (I-α-PNP), one of the most potent cytotoxic derivatives among PPs synthesized previously, between SH-SY5Y cells differentiated by all-trans-retinoic acid (ATRA) and the undifferentiated cells, and found that the differentiated cells are more sensitive to I-α-PNP toxicity than the undifferentiated cells. Treatment with I-α-PNP elicited some apoptotic alterations (Bax expression, loss of mitrochondrial membrane potential, and activation of caspases) in the differentiated cells, whose patterns were similar to those in the undifferentiated cells. I-α-PNP treatment resulted in no significant alteration in Bcl-2 expression in the undifferentiated cells, whereas it considerably downregulated the protein expression in the differentiated cells, suggesting that the high I-α-PNP sensitivity of the differentiated cells is mainly due to downregulation of Bcl-2 expression. I-α-PNP treatment decreased nitric oxide (NO) production and neuronal NOS (nNOS) expression in the differentiated cells, and the patterns of I-α-PNP-evoked alterations in phosphorylation of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression were almost the same as that in nNOS expression. Additionally, the addition of an NO donor restored the I-α-PNP-evoked alterations in expressions of Bcl-2, BDNF, and nNOS in the differentiated cells. These findings suggest that the downregulation of Bcl-2 expression by I-α-PNP in differentiated cells is attributed to the acceleration of two negative feedback loops (nNOS/NO/CREB loop and CREB/BDNF loop) triggered by decreased NO production.

Lowering of brain endothelial cell barrier function by exposure to 4'-iodo-α-pyrrolidinononanophenone.

Overuse of pyrrolidinophenones (PPs) is known to cause damage to vascular and central nervous systems, but little is known about its effect on brain endothelial barrier function. In this study, we found that exposure to 4'-iodo-α-pyrrolidinononanophenone (I-α-PNP), one of the most potently cytotoxic PPs, at sublethal concentrations decreases trans-endothelial electrical resistance and increases paracellular permeability across a monolayer of human brain microvascular endothelial cells. Treatment with I-α-PNP also elevated the production of superoxide anion. Furthermore, the treatment reduced the expression and plasma membrane localization of a tight junction protein claudin-5 (CLDN5), which was almost restored by pretreatment with an antioxidant N-acetyl-l-cysteine. These results indicate that I-α-PNP treatment may down-regulate the plasma membrane-localized CLDN5 by elevating the production of reactive oxygen species (ROS). The treatment with I-α-PNP increased the nuclear translocation of Forkhead box protein O1 (FoxO1), an oxidative stress-responsive transcription factor, and pretreating with a FoxO1 inhibitor ameliorated the decrease in CLDN5 mRNA. In addition, I-α-PNP treatment up-regulated the expression and secretion of matrix metalloproteinase-2 (MMP2) and MMP9, and the addition of an MMP inhibitor reversed the degradation of CLDN5 by I-α-PNP. Moreover, I-α-PNP treatment facilitated the activation of 26S proteasome-based proteolytic activity and pretreatment with an inhibitor of 26S proteasome, but not autophagy, suppressed the CLDN5 degradation by I-α-PNP. Accordingly, it is suggested that the down-regulation of CLDN5 by exposure to I-α-PNP is ascribable to suppression of the gene transcription due to FoxO1 nuclear translocation through ROS production and to acceleration both of the MMPs (MMP2 and MMP9)- and 26S proteasome-based proteolysis.

Covered versus uncovered metal stent for endoscopic drainage of a malignant distal biliary obstruction: Meta-analysis.

OBJECTIVES: The role of a covered vs. an uncovered self-expandable metal stent (SEMS) for malignant distal biliary obstruction (MDBO) is not clear. This meta-analysis compared the efficacy of covered vs. uncovered SEMS for patients with MDBO after endoscopic insertion. METHODS: A systematic meta-analysis of all relevant articles listed in PubMed, the Cochrane Library, and Google Scholar databases was performed. Fixed effects or random effects models were used to investigate pooled effects with 95% confidence intervals (CIs). RESULTS: The meta-analysis included 2358 patients from 12 eligible studies. Time to recurrent biliary obstruction (RBO) was significantly longer for covered SEMS (mean difference, 45.51 days; 95% CI 11.79-79.24). Although there was no significant difference in the RBO rate, subgroup analysis in pancreatic cancer occupying more than 90% (PC) revealed that the RBO rates were significantly lower for covered SEMS (odds ratio [OR] 0.43, 95% CI 0.25-0.74). Stent migration, sludge formation, and overgrowth were significantly more common with a covered SEMS (OR 7.92, 95% CI 4.01-15.64; OR 3.25, 95% CI 1.89-5.59; OR 2.03, 95% CI 1.20-3.43, respectively). The rate of ingrowth was significantly lower for covered SEMS. There was no significant difference in total procedure-related adverse events between the two types of SEMS. CONCLUSIONS: A covered SEMS is superior to an uncovered SEMS with respect to prevention of RBO in patients with MDBO, particularly those caused by PC.

Apoptotic mechanism in human brain microvascular endothelial cells triggered by 4'-iodo-α-pyrrolidinononanophenone: Contribution of decrease in antioxidant properties.

In this study, we newly synthesized four α-pyrrolidinononanophenone (α-PNP) derivatives [4'-halogenated derivatives and α-pyrrolidinodecanophenone (α-PDP)], and then performed the structure-cytotoxicity relationship analyses. The results showed the rank order for the cytotoxic effects, α-PNP < α-PDP < 4'-fluoro-α-PNP < 4'-chrolo-α-PNP < 4'-bromo-α-PNP < 4'-iodo-α-PNP (I-α-PNP), and suggest that cytotoxicities of 4'-halogenated derivatives were more intensive than that of elongation of the hydrocarbon chain (α-PDP). We also surveyed the apoptotic mechanism of I-α-PNP in brain microvascular endothelial (HBME) cells that are utilized as the in vitro model of the blood-brain barrier. HBME cell treatment with I-α-PNP facilitated the apoptotic events (caspase-3 activation, externalization of phosphatidylserine, and DNA fragmentation), which were almost completely abolished by pretreating with antioxidants. In addition, the immunofluorescent staining revealed the enhanced production of hydroxyl radical in mitochondria by the I-α-PNP treatment, inferring that the I-α-PNP treatment triggers the apoptotic mechanism dependent on the enhanced ROS production in mitochondria. The treatment with I-α-PNP increased the production of cytotoxic aldehyde 4-hydroxy-2-nonenal and decreased the amount of reduced glutathione. Additionally, the treatment decreased the 26S proteasome-based proteolytic activities and aggresome formation. These results suggest that decrease in the antioxidant properties is also ascribable to HBME cell apoptosis elicited by I-α-PNP.

Uncovered versus covered metallic stents for the management of unresectable malignant distal biliary obstruction: a randomized multicenter trial.

OBJECTIVE: The treatment result of the uncovered metallic stent (uncovered MS) and covered metallic stent (covered MS) for unresectable malignant distal biliary obstruction is controversial. This time, we conducted this study to compare the efficacies and complication rates of uncovered MS and covered MS in unresectable malignant distal biliary obstructions at a prospective randomized multicenter trial. MATERIALS AND METHODS: From April 2014 to September 2018, patients with unresectable malignant distal biliary obstruction were randomly assigned to 2 groups: the uncovered MS group and the covered MS group. RESULTS: 92 treatment results patients were discussed. 48 patients were assigned to the uncovered MS group and 44 cases were assigned to the covered MS group. Both groups showed a drainage effect. No significant difference was found in the drainage effect between the 2 groups. The number of stent occlusion was significantly greater (p = .0467) in uncovered MS (43.8%) comparing with those in covered MS (22.7%). As the cause of stent occlusion, tumor ingrowth was significantly greater (p < .001) in the uncovered MS group (35.4%) than in the covered MS group (2.3%). The median stent patency period was significantly longer (p = .0112) in the covered MS group (455 days) than that of the uncovered MS group (301 days). A significant difference in the median survival period was not found between the 2 groups. CONCLUSIONS: Covered MS showed the possibility of extending the stent patency period by suppressing tumor ingrowth more than uncovered MS does. The UMIN Clinical Trial Registry number is UMIN000015093.

Current status of diagnosis and therapy for intraductal papillary neoplasm of the bile duct.

Bile duct epithelial tumours showing papillary neoplasm in the bile duct lumen are present in the intrahepatic and extrahepatic bile ducts. Clinicopathological images of these tumours are distinctive and diverse, including histological images with a low to high grade dysplasia, infiltrating and noninfiltrating characteristics, excessive mucus production, and similarity to intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The World Health Organization Classification of Tumours of the Digestive System in 2010 named these features, intraductal papillary neoplasm of the bile duct (IPNB), as precancerous lesion of biliary carcinoma. IPNB is currently classified into type 1 that is similar to IPMN, and type 2 that is not similar to IPMN. Many of IPNB spreads superficially, and diagnosis with cholangioscopy is considered mandatory to identify accurate localization and progression. Prognosis of IPNB is said to be better than normal bile duct cancer.

Percutaneous Two-Dimensional Shear Wave Elastography for Diagnosis of Pancreatic Tumor.

BACKGROUND: To investigate the efficacy of two-dimensional shear wave elastography (2D-SWE) for the diagnosis of pancreatic mass lesions. METHODS: This ethics committee-approved cross-sectional study included 52 patients with histologically-proven pancreatic tumors (pancreatic ductal adenocarcinoma (PDAC), 36; tumor-forming pancreatitis (TFP), 15; neuroendocrine tumor, 1) and 33 control subjects. The 2D-SWE was performed for the tumor/non-tumor tissues, and SWE-mapping patterns and propagation quality were assessed. RESULTS: Three mapping patterns were detected based on the size and distribution of the coloring areas. Pattern A (whole coloring) was detected in all non-tumor tissues and TFP, whereas pattern C (multiple small coloring spots) was detected in PDAC only. Pattern B (partial coloring with smaller spots) was detected in other lesions. The specificity and positive predictive value of pattern A for non-PDAC and those of pattern C for PDAC were 100%. The SWE value was higher in tumor lesions than in the non-tumor tissues (38.1 vs. 9.8 kPa; p < 0.001) in patients with PDAC. The SWE value in the non-tumor lesion was higher in patients with PDAC than in control (9.8 vs. 7.5 kPa; p < 0.001). CONCLUSIONS: 2D-SWE may play a role as a novel diagnostic tool for PDAC to detect a specific mapping pattern with quantitative assessment.

Modeling Membrane Morphological Change during Autophagosome Formation.

Autophagy is an intracellular degradation process that is mediated by de novo formation of autophagosomes. Autophagosome formation involves dynamic morphological changes; a disk-shaped membrane cisterna grows, bends to become a cup-shaped structure, and finally develops into a spherical autophagosome. We have constructed a theoretical model that integrates the membrane morphological change and entropic partitioning of putative curvature generators, which we have used to investigate the autophagosome formation process quantitatively. We show that the membrane curvature and the distribution of the curvature generators stabilize disk- and cup-shaped intermediate structures during autophagosome formation, which is quantitatively consistent with in vivo observations. These results suggest that various autophagy proteins with membrane curvature-sensing properties control morphological change by stabilizing these intermediate structures. Our model provides a framework for understanding autophagosome formation.

Endoscopic Ultrasound Criteria for Arterial Invasion in Pancreatic Cancer of the Body and Tail.

OBJECTIVES: We aimed to determine the difference in endoscopic ultrasonography (EUS) images between portal vein (PV) and arterial invasion of pancreatic cancer and to develop criteria for arterial involvement. METHODS: We reviewed EUS data of consecutive patients who underwent distal pancreatectomy from December 2010 to May 2017. We categorized the tumor-vessel relationship into 4 and 5 types, respectively, for the PV and arteries: (a) clear separation between tumor and vessel; (b) tumor border at vessel, echo-rich vessel wall uninterrupted; (c) echo-rich vessel wall interrupted; (d) vessel contour irregularity; and (e) arterial wall thickening or echogenic band surrounding the artery. We compared EUS outcomes with surgical and pathological results. RESULTS: Overall, 56 patients underwent distal pancreatectomy, of whom 22 received en bloc celiac axis resection. The pathological invasion rates of PVs and arteries were 46.2% and 0% in (c), and 72.5% and 42.4% in (d) (P = 0.046, P = 0.016), respectively. The overall sensitivity and specificity were 92.1% and 83.2%, respectively, for diagnosing venous invasion and 70.0% and 84.4%, respectively, for arterial invasion. CONCLUSIONS: Different EUS criteria may be necessary for diagnosing arterial and portal venous invasions. Criterion (d) might be appropriate for diagnosing arterial invasion.

Molecular Dynamics Simulations of Condensin-Mediated Mitotic Chromosome Assembly.

Molecular dynamics simulation is a powerful tool used in modern molecular modeling, which enables a deeper comprehension of the physical behavior of atoms and molecules at a micro level. In this study, we simulated mitotic chromosome assembly mediated by condensins, a class of large protein complexes containing a pair of structural maintenance of chromosomes (SMC) subunits that are central to this process. In this chapter, we present the construction of a coarse-grained physical model of chromosomal DNA fibers and condensin molecules, and monitoring of the function of condensins in mitotic chromosome assembly, using computer-based molecular dynamics simulation. We explain how our model of chromosomes and condensins may be simulated using a package of molecular dynamics simulation. Procedures involved in calculating the observables of dynamics are described, together with an example of the simulation results.