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Betulinic acid (BA) is a naturally arising pentacyclic triterpenoid that has anti-malarial, anti-retroviral, anti-inflammatory, and anti-cancer biological effects. More recently, it has been reported to possess anti-obesity activity mediated by the activation of AMP-activated protein kinase (AMPK). We further investigated antidiabetic activity of BA in mouse tissues at the cellular and systemic levels. We found that BA stimulated AMPK in a similar fashion to the known AMPK activators, such as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside and metformin. Notably, the level of glucose uptake by BA was not altered by wortmannin, suggesting that this activation did not depend on phosphoinositide 3-kinase. Furthermore, BA diminished blood glucose levels in alloxane-treated ICR mice and in untreated mice during the glucose tolerance test. BA also stimulated mRNA expression of glucose transporter 4, which could partly explain increased glucose uptake. BA also increased AS160 phosphorylation by insulin-independent mechanisms in the extensor digitorum longus muscle. These results indicate that BA may serve as a promising therapeutic agent for diabetes by activating AMPK, like metformin. Notably, BA also enhanced mouse endurance capacity, indicating that it also affects metabolic regulation in addition to its antidiabetic activity.

Mucinous cystic neoplasms (MCN) and serous cystic neoplasms (SCN) account for a large portion of solitary pancreatic cystic neoplasms (PCN). In this study we implemented a convolutional neural network (CNN) model using ResNet50 to differentiate between MCN and SCN. The training data were collected retrospectively from 59 MCN and 49 SCN patients from two different hospitals. Data augmentation was used to enhance the size and quality of training datasets. Fine-tuning training approaches were utilized by adopting the pre-trained model from transfer learning while training selected layers. Testing of the network was conducted by varying the endoscopic ultrasonography (EUS) image sizes and positions to evaluate the network performance for differentiation. The proposed network model achieved up to 82.75% accuracy and a 0.88 (95% CI: 0.817–0.930) area under curve (AUC) score. The performance of the implemented deep learning networks in decision-making using only EUS images is comparable to that of traditional manual decision-making using EUS images along with supporting clinical information. Gradient-weighted class activation mapping (Grad-CAM) confirmed that the network model learned the features from the cyst region accurately. This study proves the feasibility of diagnosing MCN and SCN using a deep learning network model. Further improvement using more datasets is needed.

Formic acid is considered a promising hydrogen carrier. Biomass‐derived formic acid can be obtained by oxidative decomposition of sugars. This study explored the production of formic acid from cellobiose, a disaccharide consisting of d‐glucose linked by β‐glycosidic bonds using heterogeneous catalysts under mild reaction conditions. The use of alkaline earth metal oxide solid base catalysts like CaO and MgO in the presence of hydrogen peroxide could afford formic acid from cellobiose at 343 K. While CaO gave 14 % yield of formic acid, the oxide itself was converted to a harmful metal peroxide, CaO2 after the reaction. In contrast, MgO could produce formic acid without the formation of the metal peroxide. The difficulty in selectively synthesizing formic acid from cellobiose using these solid base catalysts was due to the poor conversion of cellobiose to glucose. Using a combination of solid acid and base catalysts, a high formic acid yield of 33 % was obtained under mild reaction conditions due to the quantitative hydrolysis of cellobiose to glucose by a solid acid followed by the selective decomposition of glucose to formic acid by a solid base. The oxidative conversion of the disaccharide cellobiose to formic acid was carried out. Formic acid was produced in the presence of hydrogen peroxide using solid base catalysts such as CaO and MgO, but the low yield was low. A two‐step one pot synthesis using solid acid and base catalysts improved the formic acid yield under mild reaction conditions.

(1) Background: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an alternative treatment for pancreatic tumors. Currently, EUS-RFA has been trialled to treat hepatic tumors. However, little has been reported about optimal settings for EUS-RFA in patients with hepatic tumors. We evaluated the ablation effect after in vivo RFA using a new EUS-RFA electrode in a pig model. (2) Methods Four pigs were used for the in vivo test. The in vivo testing was divided into two tests based on the length of the RFA electrode (0.5, 0.7, 1 or 1.5 cm), the ablation power (30 W or 50 W), and the ablation time (10 or 15 s). In test one, ablation effect was evaluated based on the electrode length and power. In test two, ablation effect was assessed based on power and time. (3) Results: In test one, the ablation width and depth correlated with the length of the electrode and power (0.5 cm, 10 W, 10 s: width 0.46 cm, depth 0.65 cm vs. 1.5 cm, 75 W, 10 s: width 0.77 cm, depth 1.80 cm). In test two, ablation width and depth were similar when RFA was set at 1.5cm, 50 W, and 10 s or 1 cm, 30 W, and 15 s (0.65 cm, 1.14 cm vs. 0.65cm, 1.26 cm). (4) Conclusions: The relationship between electrode length, ablation power, and ablation time, and the resulting ablation effect in pig livers suggest that EUS-RFA produces effective ablation while minimizing thermal injury.

ObjectivesThe goal of the study was to determine whether endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is comparable to conventional transpapillary stenting with endoscopic retrograde cholangiopancreatography (ERCP) in palliation of malignant distal biliary obstruction. Although ERCP for the palliation of malignant biliary obstruction is the standard of care, post-procedure pancreatitis and stent dysfunctions are not uncommon. While EUS-BD has garnered interest as a viable alternative when ERCP is impossible, its role as a primary palliation of malignant distal biliary obstruction is yet to be proven.MethodsWe performed random allocation to EUS-BD or ERCP in 125 patients with unresectable malignant distal biliary obstruction at four tertiary academic referral centers in South Korea.ResultsTechnical success rates were 93.8% (60/64) for EUS-BD and 90.2% (55/61) for ERCP (difference 3.6%, 95% 1-sided confidence interval lower limit −4.4%, P = 0.003 for noninferiority margin of 10%). Clinical success rates were 90.0% (54/60) in EUS-BD and 94.5% (52/55) in ERCP (P = 0.49). Lower rates of overall adverse events (6.3% vs 19.7%, P = 0.03) including post-procedure pancreatitis (0 vs 14.8%), reintervention (15.6% vs 42.6%), and higher rate of stent patency (85.1% vs 48.9%) were observed with EUS-BD. EUS-BD was also associated with more preserved quality of life (QOL) than transpapillary stenting after 12 weeks of the procedure.ConclusionsThis study demonstrated comparable technical and clinical success rates between EUS-BD and ERCP in relief of malignant distal biliary obstruction. Substantially longer duration of patency coupled with lower rates of adverse events and reintervention, and more preserved QOL were observed with EUS-BD (cris.nih.go.kr, Identifier: KCT0001396, https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=9716<ype=&rtype=).

Resveratrol is a phytochemical with medicinal benefits, being well-known for its presence in wine. Plants develop resveratrol in response to stresses such as pathogen infection, UV radiation, and other mechanical stress. The recent publications of genomic sequences of resveratrol-producing plants such as grape, peanut, and eucalyptus can expand our molecular understanding of resveratrol synthesis. Based on a gene family count matrix of Viridiplantae members, we uncovered important gene families that are common in resveratrol-producing plants. These gene families could be prospective candidates for improving the efficiency of synthetic biotechnology-based artificial resveratrol manufacturing.

Stereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC. We retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24-36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed. A total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients. LAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.

Squaraine dyes are organic dyes having strong and narrow absorption properties in the near-infrared region that are widely used in photovoltaic and biomedical applications. In this work, squaraine dye ( SA1 ) was synthesized as a dye sensitizer for a dye-sensitized photocatalytic system, which was composed of SA1 and Pt-loaded TiO 2 powder photocatalyst ( SA1 /Pt-TiO 2 ). The SA1 /Pt-TiO 2 system exhibited a good hydrogen production performance within 150 h and an apparent quantum yield of 1.4% under 800 nm monochromatic light irradiation. However, during the photocatalytic reaction, the photocatalytic activity of SA1 /Pt-TiO 2 decreased due to photodecomposition. Ultraviolet–visible absorption spectroscopy, 1 H nuclear magnetic resonance spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry measurements were performed to investigate the mechanism of the decomposition of the squaraine moiety of SA1 , the decomposition process, and the structure of the decomposed material. The results show that even without the Pt-loaded TiO 2 powder photocatalyst, SA1 undergoes photodissociation, which cleaves the bond between the indoline moiety and the square acid. Graphical abstract

BackgroundType 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation of IgG4-related disease, shows a favorable prognosis in the short term. However, disease relapse is common in long-term follow-up, despite a successful initial treatment response. This study aimed to identify the predictors of relapse and long-term outcomes in patients with type 1 AIP.MethodsPatients with more than 2 years of follow-up who met the International Consensus Diagnostic Criteria for type 1 AIP were included. Patients who had undergone pancreatic operations associated with AIP or who lacked sufficient clinical data were excluded.ResultsAll 138 patients achieved clinical remission with initial steroid therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24–197) months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within 3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of the proximal bile duct, was a significant independent predictor of relapse (hazard ratio 2.65; 95% confidence interval 1.44–4.89; p = 0.002), according to multivariate analysis. During the follow-up period, 16 (11.6%) patients experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de novo pancreatic calcifications/stones. No pancreatic cancer occurred in any patients.ConclusionsType 1 AIP has common relapses, and patients with OOI, especially OOI of the proximal bile duct, appear to be at increased risk for relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic calcifications/stones, are common in patients with relapse. To reduce the relapse, longer maintenance treatment may be needed especially for patients at high risk for relapse.

Background: Although endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) with transmural stenting has increased for biliary decompression in patients with an inaccessible papilla, the optimal biliary access point and the learning curve of EUS-HGS have not been studied. We evaluated the optimal biliary access point and learning curve for technically successful EUS-HGS. Methods: 129 consecutive patients (male n = 81, 62.3%; malignant n = 113, 87.6%) who underwent EUS-HGS due to an inaccessible papilla were enrolled. EUS finding and procedure times according to each needle puncture attempt in EUS-HGS were prospectively measured. Learning curves of EUS-HGS were calculated for two main outcome measurements (procedure time and adverse events) by using the moving average method and cumulative sum (CUSUM) analysis, respectively. Results: A total of 174 EUS-HGS attempts were performed in 129 patients. The mean number of needle punctures was 1.35 ± 0.57. Using the logistic regression model, bile duct diameter of the puncture site ⩽ 5 mm [odds ratio (OR) 3.7, 95% confidence interval (CI): 1.71–8.1, p < 0.01] and hepatic portion length [linear distance from the mural wall to the punctured bile duct wall on EUS; mean hepatic portion length was 27 mm (range 10–47 mm)] > 3 cm (OR 5.7, 95% CI: 2.7–12, p < 0.01) were associated with low technical success. Procedure time and adverse events were shorter after 24 cases, and stabilized at 33 cases of EUS-HGS, respectively. Conclusions: Our data suggest that a bile duct diameter > 5 mm and hepatic portion length 1 cm to ⩽ 3 cm on EUS may be suitable for successful EUS-HGS. In our learning curve analysis, over 33 cases might be required to achieve the plateau phase for successful EUS-HGS.