FOXP3 recognizes microsatellites and bridges DNA through multimerization.

FOXP3 is a transcription factor that is essential for the development of regulatory T cells, a branch of T cells that suppress excessive inflammation and autoimmunity1-5. However, the molecular mechanisms of FOXP3 remain unclear. Here we here show that FOXP3 uses the forkhead domain-a DNA-binding domain that is commonly thought to function as a monomer or dimer-to form a higher-order multimer after binding to TnG repeat microsatellites. The cryo-electron microscopy structure of FOXP3 in a complex with T3G repeats reveals a ladder-like architecture, whereby two double-stranded DNA molecules form the two 'side rails' bridged by five pairs of FOXP3 molecules, with each pair forming a 'rung'. Each FOXP3 subunit occupies TGTTTGT within the repeats in a manner that is indistinguishable from that of FOXP3 bound to the forkhead consensus motif (TGTTTAC). Mutations in the intra-rung interface impair TnG repeat recognition, DNA bridging and the cellular functions of FOXP3, all without affecting binding to the forkhead consensus motif. FOXP3 can tolerate variable inter-rung spacings, explaining its broad specificity for TnG-repeat-like sequences in vivo and in vitro. Both FOXP3 orthologues and paralogues show similar TnG repeat recognition and DNA bridging. These findings therefore reveal a mode of DNA recognition that involves transcription factor homomultimerization and DNA bridging, and further implicates microsatellites in transcriptional regulation and diseases.

Two different jumping mechanisms of water striders are determined by body size.

Current theory for surface tension-dominant jumps on water, created for small- and medium-sized water strider species and used in bioinspired engineering, predicts that jumping individuals are able to match their downward leg movement speed to their size and morphology such that they maximize the takeoff speed and minimize the takeoff delay without breaking the water surface. Here, we use empirical observations and theoretical modeling to show that large species (heavier than ~80 mg) could theoretically perform the surface-dominated jumps according to the existing model, but they do not conform to its predictions, and switch to using surface-breaking jumps in order to achieve jumping performance sufficient for evading attacks from underwater predators. This illustrates how natural selection for avoiding predators may break the theoretical scaling relationship between prey size and its jumping performance within one physical mechanism, leading to an evolutionary shift to another mechanism that provides protection from attacking predators. Hence, the results are consistent with a general idea: Natural selection for the maintenance of adaptive function of a specific behavior performed within environmental physical constraints leads to size-specific shift to behaviors that use a new physical mechanism that secure the adaptive function.

Impact of the Supra-papilla Method on Patency in Distal Malignant Biliary Obstruction: A Multicenter Randomized Controlled Trial.

BACKGROUND: /aims: Placement of a self-expandable metal stent (SEMS) across the duodenal major papilla carries a risk of duodenobiliary reflux (DBR). The supra-papilla method of stenting may reduce DBR and improve stent patency compared to the trans-papilla method. This study aimed to compare the clinical outcomes between the supra-papilla and trans-papilla methods for distal malignant biliary obstruction (DMBO). METHODS: Between January 2021 and January 2023, consecutive patients with DMBO from six centers in Korea were randomly assigned to either the supra-papilla or trans-papilla method arm in a 1:1 ratio. The primary outcome was the duration of stent patency, and secondary outcomes included the cause of stent dysfunction, adverse events, and overall survival rate. RESULTS: A total of 84 patients were equally assigned to each group. The most common cause of DMBO was pancreatic cancer (n=50, 59.5%), followed by bile duct (n=20, 23.8%), gallbladder (n=11, 13.1%), and other cancers (n=3, 3.6%). Stent patency was significantly longer in the supra-papilla group (median [95% confidence interval], 369 [289-497] vs. 154 [78-361] days; P < 0.01). Development of DBR was significantly lower in the supra-papilla group (9.4% vs 40.8%, P < 0.01). Adverse events and overall survival rate were not significantly different between the two groups. CONCLUSIONS: The placement of SEMS using the supra-papilla method resulted in a significantly longer duration of stent patency. It is advisable to place the SEMS using the supra-papilla method in DMBO. Further studies with a larger number of patients are required to validate the benefits of the supra-papilla method.

Integrating Biomarkers From Virtual Reality and Magnetic Resonance Imaging for the Early Detection of Mild Cognitive Impairment Using a Multimodal Learning Approach: Validation Study.

BACKGROUND: Early detection of mild cognitive impairment (MCI), a transitional stage between normal aging and Alzheimer disease, is crucial for preventing the progression of dementia. Virtual reality (VR) biomarkers have proven to be effective in capturing behaviors associated with subtle deficits in instrumental activities of daily living, such as challenges in using a food-ordering kiosk, for early detection of MCI. On the other hand, magnetic resonance imaging (MRI) biomarkers have demonstrated their efficacy in quantifying observable structural brain changes that can aid in early MCI detection. Nevertheless, the relationship between VR-derived and MRI biomarkers remains an open question. In this context, we explored the integration of VR-derived and MRI biomarkers to enhance early MCI detection through a multimodal learning approach. OBJECTIVE: We aimed to evaluate and compare the efficacy of VR-derived and MRI biomarkers in the classification of MCI while also examining the strengths and weaknesses of each approach. Furthermore, we focused on improving early MCI detection by leveraging multimodal learning to integrate VR-derived and MRI biomarkers. METHODS: The study encompassed a total of 54 participants, comprising 22 (41%) healthy controls and 32 (59%) patients with MCI. Participants completed a virtual kiosk test to collect 4 VR-derived biomarkers (hand movement speed, scanpath length, time to completion, and the number of errors), and T1-weighted MRI scans were performed to collect 22 MRI biomarkers from both hemispheres. Analyses of covariance were used to compare these biomarkers between healthy controls and patients with MCI, with age considered as a covariate. Subsequently, the biomarkers that exhibited significant differences between the 2 groups were used to train and validate a multimodal learning model aimed at early screening for patients with MCI among healthy controls. RESULTS: The support vector machine (SVM) using only VR-derived biomarkers achieved a sensitivity of 87.5% and specificity of 90%, whereas the MRI biomarkers showed a sensitivity of 90.9% and specificity of 71.4%. Moreover, a correlation analysis revealed a significant association between MRI-observed brain atrophy and impaired performance in instrumental activities of daily living in the VR environment. Notably, the integration of both VR-derived and MRI biomarkers into a multimodal SVM model yielded superior results compared to unimodal SVM models, achieving higher accuracy (94.4%), sensitivity (100%), specificity (90.9%), precision (87.5%), and F1-score (93.3%). CONCLUSIONS: The results indicate that VR-derived biomarkers, characterized by their high specificity, can be valuable as a robust, early screening tool for MCI in a broader older adult population. On the other hand, MRI biomarkers, known for their high sensitivity, excel at confirming the presence of MCI. Moreover, the multimodal learning approach introduced in our study provides valuable insights into the improvement of early MCI detection by integrating a diverse set of biomarkers.

Comparative efficacies and safeties of cylindrical interstitial laser ablation and radiofrequency ablation on swine pancreas.

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.

Exploring the Relationship between Behavioral and Neurological Impairments Due to Mild Cognitive Impairment: Correlation Study between Virtual Kiosk Test and EEG-SSVEP.

Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal aging and Alzheimer's disease, making early screening imperative for potential intervention and prevention of progression to Alzheimer's disease (AD). Therefore, there is a demand for research to identify effective and easy-to-use tools for aMCI screening. While behavioral tests in virtual reality environments have successfully captured behavioral features related to instrumental activities of daily living for aMCI screening, further investigations are necessary to establish connections between cognitive decline and neurological changes. Utilizing electroencephalography with steady-state visual evoked potentials, this study delved into the correlation between behavioral features recorded during virtual reality tests and neurological features obtained by measuring neural activity in the dorsal stream. As a result, this multimodal approach achieved an impressive screening accuracy of 98.38%.

Finding the ideal sedative: a non-inferiority study of remimazolam vs propofol in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) requires an ideal sedative that provides a predictable action duration and meets safety requirements. We compared the efficacies and safeties of remimazolam and propofol in patients who had undergone ERCP. METHODS: In this prospective, randomized, single-blind, single-center study, we compared the performances of remimazolam and propofol for inpatient ERCP. Study medications were administered under the supervision of an endoscopist. One hundred and ten patients scheduled to undergo ERCP were randomly assigned to receive remimazolam or propofol. The primary endpoint was a composite of successful completion of the procedure and no requirement for rescue medication. Secondary endpoints included sedation efficacy, recovery time, and adverse events. RESULTS: Of the 110 patients randomized, 108 underwent sedation, and ERCP (53 received remimazolam and 55 propofol). The primary endpoint was met for remimazolam and propofol in 100% of patients in both arms. Incidences and frequencies of emergent adverse events, including desaturation, requiring treatment were comparable in both arms. However, ERCP was started sooner in the propofol arm (mean, 63.18 ± 16.56 s) than in the remimazolam arm (75.23 ± 32.27 s; P-value = 0.02). Time to full alertness after ERCP was also significantly shorter in the propofol arm (304.18 ± 146.25 vs 448.34 ± 224.09 s; P-value <0.001). CONCLUSION: Remimazolam is not inferior to propofol in achieving successful ERCP completion without rescue medication. Incidences of adverse events were comparable. Remimazolam is a safe and effective alternative to propofol for ERCP sedation, expanding options for clinicians and improving patient outcomes.

Comparison of the long-term outcomes between proximal and distal IgG4-related sclerosing cholangitis: A multicenter cohort study.

BACKGROUND AND AIMS: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is considered a biliary manifestation of IgG4-related diseases. However, there has been a controversy on the clinical outcomes according to the location of the involved bile duct. We therefore compared the clinical outcomes and long-term prognosis of IgG4-SC with proximal bile duct involvement (proximal IgG4-SC) and IgG4-SC with distal bile duct involvement (distal IgG4-SC). METHODS: We reviewed the data of patients with IgG4-SC that were prospectively collected at 10 tertiary centers between March 2002 and October 2020. Clinical manifestations, outcomes, association with autoimmune pancreatitis (AIP), steroid-responsiveness, and relapse of IgG4-SC were evaluated. RESULTS: A total of 148 patients (proximal IgG4-SC, n = 59; distal IgG4-SC, n = 89) were analyzed. The median age was 65 years (IQR, 56.25-71), and 86% were male. The two groups were similar in terms of jaundice at initial presentation (51% vs 65%; P = 0.082) and presence of elevated serum IgG4 (66% vs 70%; P = 0.649). The two groups showed significant differences in terms of steroid-responsiveness (91% vs 100%; P = 0.008), association with AIP (75% vs 99%; P = 0.001), and occurrence of liver cirrhosis (9% vs 1%; P = 0.034). During a median follow-up of 64 months (IQR, 21.9-84.7), the cumulative relapse-free survival was significantly different between the two groups (67% vs 79% at 5 years; P = 0.035). CONCLUSIONS: Relapse of IgG4-SC frequently occurred during follow-up. Proximal IgG4-SC and distal IgG4-SC had different long-term outcomes in terms of steroid-responsiveness, occurrence of liver cirrhosis, and recurrence. It may be advantageous to determine the therapeutic and follow-up strategies according to the location of bile duct involvement.

Trash to Treasure: An Up-to-Date Understanding of the Valorization of Seafood By-Products, Targeting the Major Bioactive Compounds.

Fishery production is exponentially growing, and its by-products negatively impact industries' economic and environmental status. The large amount of bioactive micro- and macromolecules in fishery by-products, including lipids, proteins, peptides, amino acids, vitamins, carotenoids, enzymes, collagen, gelatin, chitin, chitosan, and fucoidan, need to be utilized through effective strategies and proper management. Due to the bioactive and healthy compounds in fishery discards, these components can be used as functional food ingredients. Fishery discards have inorganic or organic value to add to or implement in various sectors (such as the agriculture, medical, and pharmaceutical industries). However, the best use of these postharvest raw materials for human welfare remains unelucidated in the scientific community. This review article describes the most useful techniques and methods, such as obtaining proteins and peptides, fatty acids, enzymes, minerals, and carotenoids, as well as collagen, gelatin, and polysaccharides such as chitin-chitosan and fucoidan, to ensure the best use of fishery discards. Marine-derived bioactive compounds have biological activities, such as antioxidant, anticancer, antidiabetic, anti-inflammatory, and antimicrobial activities. These high-value compounds are used in various industrial sectors, such as the food and cosmetic industries, owing to their unique functional and characteristic structures. This study aimed to determine the gap between misused fishery discards and their effects on the environment and create awareness for the complete valorization of fishery discards, targeting a sustainable world.

Exploring Bioactive Compounds in Brown Seaweeds Using Subcritical Water: A Comprehensive Analysis.

In this study, we characterized the bioactive properties of three important brown seaweed species, Sargassum thunbergii, Undaria pinnatifida, and Saccharina japonica, by subcritical water extraction (SWE), as these species are well known for their beneficial health effects. Their physiochemical properties, including potential antioxidant, antihypertensive, and α-glucosidase inhibitory activity, and the antibacterial activity of the hydroysates were also analyzed. The highest total phlorotannin, total sugar content, and reducing sugar content in the S. thunbergii hydrolysates were 38.82 ± 0.17 mg PGE/g, 116.66 ± 0.19 mg glucose/g dry sample, and 53.27 ± 1.57 mg glucose/g dry sample, respectively. The highest ABTS+ and DPPH antioxidant activities were obtained in the S. japonica hydrolysates (124.77 ± 2.47 and 46.35 ± 0.01 mg Trolox equivalent/g, respectively) and the highest FRAP activity was obtained in the S. thunbergii hydrolysates (34.47 ± 0.49 mg Trolox equivalent/g seaweed). In addition, the seaweed extracts showed antihypertensive (≤59.77 ± 0.14%) and α-glucosidase inhibitory activity (≤68.05 ± 1.15%), as well as activity against foodborne pathogens. The present findings provide evidence of the biological activity of brown seaweed extracts for potential application in the food, pharmaceutical, and cosmetic sectors.

Digital Marker for Early Screening of Mild Cognitive Impairment Through Hand and Eye Movement Analysis in Virtual Reality Using Machine Learning: First Validation Study.

BACKGROUND: With the global rise in Alzheimer disease (AD), early screening for mild cognitive impairment (MCI), which is a preclinical stage of AD, is of paramount importance. Although biomarkers such as cerebrospinal fluid amyloid level and magnetic resonance imaging have been studied, they have limitations, such as high cost and invasiveness. Digital markers to assess cognitive impairment by analyzing behavioral data collected from digital devices in daily life can be a new alternative. In this context, we developed a "virtual kiosk test" for early screening of MCI by analyzing behavioral data collected when using a kiosk in a virtual environment. OBJECTIVE: We aimed to investigate key behavioral features collected from a virtual kiosk test that could distinguish patients with MCI from healthy controls with high statistical significance. Also, we focused on developing a machine learning model capable of early screening of MCI based on these behavioral features. METHODS: A total of 51 participants comprising 20 healthy controls and 31 patients with MCI were recruited by 2 neurologists from a university hospital. The participants performed a virtual kiosk test-developed by our group-where we recorded various behavioral data such as hand and eye movements. Based on these time series data, we computed the following 4 behavioral features: hand movement speed, proportion of fixation duration, time to completion, and the number of errors. To compare these behavioral features between healthy controls and patients with MCI, independent-samples 2-tailed t tests were used. Additionally, we used these behavioral features to train and validate a machine learning model for early screening of patients with MCI from healthy controls. RESULTS: In the virtual kiosk test, all 4 behavioral features showed statistically significant differences between patients with MCI and healthy controls. Compared with healthy controls, patients with MCI had slower hand movement speed (t49=3.45; P=.004), lower proportion of fixation duration (t49=2.69; P=.04), longer time to completion (t49=-3.44; P=.004), and a greater number of errors (t49=-3.77; P=.001). All 4 features were then used to train a support vector machine to distinguish between healthy controls and patients with MCI. Our machine learning model achieved 93.3% accuracy, 100% sensitivity, 83.3% specificity, 90% precision, and 94.7% F1-score. CONCLUSIONS: Our research preliminarily suggests that analyzing hand and eye movements in the virtual kiosk test holds potential as a digital marker for early screening of MCI. In contrast to conventional biomarkers, this digital marker in virtual reality is advantageous as it can collect ecologically valid data at an affordable cost and in a short period (5-15 minutes), making it a suitable means for early screening of MCI. We call for further studies to confirm the reliability and validity of this approach.

Hemostatic efficacy and safety of the hemostatic powder UI-EWD in patients with lower gastrointestinal bleeding.

BACKGROUND AND AIMS: Acute lower gastrointestinal bleeding (LGIB) is a common cause of emergency hospitalization and may require readmission for re-bleeding. Recently, a novel endoscopic hemostatic powder (UI-EWD/Nexpowder™, Nextbiomedical, Incheon, South Korea) was developed and applied for the control of LGIB. The aim of this study was to evaluate the hemostatic efficacy and long-term safety of UI-EWD in LGIB. PATIENTS AND METHODS: We conducted a retrospective cohort study of LGIB at a single tertiary center in south Korea. One hundred and sixty-seven consecutive patients with LGIB who were initially successful in endoscopic hemostasis were included and divided into the conventional treatment group (n = 112) and the UI-EWD therapy group (n = 55; 38 patients with conventional treatment and 17 patients with UI-EWD alone). The success rate of hemostasis, adverse events related to UI-EWD, and re-bleeding rate were evaluated. RESULTS: The incidence of endoscopic hemostasis applied to the hepatic flexure (7.3% vs. 0%, p = 0.011) and larger than 4 cm (25.5% vs. 8.0%, p = 0.002) were significantly higher in the UI-EWD group than in the conventional therapy group. The cumulative rebleeding rate within 28 days in the UI-EWD group was 5.5% (3/55), which was significantly lower than that in the conventional treatment group (17.0% [19/112]; p = 0.039). No UI-EWD-related adverse events were recorded. CONCLUSION: Based on our results, application of UI-EWD in LGIB showed promising results for the prevention of re-bleeding, especially in locations where it is difficult to approach or cases with more bleeding. There were no significant complications, such as perforation or embolism. In particular, UI-EWD should be considered first for anatomical or technical impediments to endoscopic access in LGIB.

Efficacy analysis of hemostatic spray following endoscopic papillectomy: A multicenter comparative study.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding is a serious adverse event with a prevalence ranging from 2% to 45.3%. Conventional hemostatic methods, including diluted epinephrine injection before papillectomy or argon plasma coagulation after papillectomy, did not show a preventive role in reducing immediate or delayed post-papillectomy bleeding. Therefore, we aimed to assess the efficacy and safety of a hemostatic powder spray for post-papillectomy bleeding and compare with those of conventional modalities. METHODS: Patients who underwent endoscopic papillectomy were enrolled in five tertiary hospitals. The group was divided into hemostatic spray and conventional control groups according to the bleeding control methods. The main outcome measurements were delayed bleeding rate and any adverse events related to the procedures. RESULTS: A total of 40 patients who received a hemostatic spray (n = 18) or conventional hemostatic methods (n = 22) after endoscopic papillectomy were included. The prevalence of delayed bleeding was not different in the two groups: 27.8% and 36.4% in hemostatic spray and conventional control groups (P = 0.564), respectively. The adverse events such as post-papillectomy pancreatitis and cholangitis were not different in the two groups. There were no procedure-related mortalities. CONCLUSION: Hemostatic spray is technically feasible and safe for the prevention or management of post-papillectomy bleeding. Hemostatic spray can be one of the options for post-papillectomy bleeding control methods owing to its convenient use.

Impact of High-Flow Nasal Cannula Oxygenation on the Prevention of Hypoxia During Endoscopic Retrograde Cholangiopancreatography in Elderly Patients: A Randomized Clinical Trial.

BACKGROUND: Hypoxia is the most frequently occurring adverse effect during endoscopic retrograde cholangiopancreatography (ERCP) under sedation; thus, oxygen must be properly supplied to prevent a reduction of oxygen saturation. In this study, we intend to verify the preventive effect for hypoxia during ERCP, using a high-flow nasal cannula (HFNC), in elderly patients. METHODS: As a multicenter prospective randomized trial, patients who underwent ERCP with propofol-based sedation were randomly assigned into two groups: Patients in the HFNC group were supplied with oxygen via an HFNC, and those in the standard nasal cannula group were supplied with oxygen via a low-flow nasal cannula. The co-primary end points were the lowest oxygen saturation rate and hypoxia during the overall procedure. RESULTS: A total of 187 patients (HFNC group: 95; standard nasal cannula group: 92) were included in the analysis. Unexpected hypoxia events were more frequently observed among patients in the standard nasal cannula group than among patients in the HFNC group (13% vs. 4%, odds ratio 3.41, 95% confidence interval 1.06-11.00, p = 0.031). The mean of the lowest oxygen saturation rate during ERCP was significantly lower in the standard nasal cannula group than in the HFNC group (95% vs. 97%, p = 0.002). CONCLUSION: Oxygen supplementation with an HFNC can prevent oxygen desaturation and hypoxia events in patients undergoing ERCP under sedation. Trial registration Clinical Research Information Service (CRIS; KCT0004960).

The impact of preoperative EUS-FNA for distal resectable pancreatic cancer: Is it really effective enough to take risks?

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently used for the preoperative histologic diagnosis of pancreatic cancer. However, debate continues regarding the clinical merits of preoperative EUS-FNA for the management of resectable pancreatic cancer. We aimed to evaluate the benefits and safety of preoperative EUS-FNA for resectable distal pancreatic cancer. METHODS: The medical records of 304 consecutive patients with suspected distal pancreatic cancer who underwent EUS-FNA were retrospectively reviewed to evaluate the clinical benefits of preoperative EUS-FNA. We also reviewed the medical records of 528 patients diagnosed with distal pancreatic cancer who underwent distal pancreatectomy with or without EUS-FNA. The recurrence rates and cancer-free survival periods of patients who did or did not undergo preoperative EUS-FNA were compared. RESULTS: The diagnostic accuracy of preoperative EUS-FNA was high (sensitivity, 87.5%; specificity, 100%; positive predictive value 100%; accuracy, 90.7%; negative predictive value, 73.8%). Among patients, 26.7% (79/304) avoided surgery based on the preoperative EUS-FNA findings. Of the 528 patients who underwent distal pancreatectomy, 193 patients received EUS-FNA and 335 did not. During follow-up (median 21.7 months), the recurrence rate was similar in the two groups (EUS-FNA, 72.7%; non-EUS-FNA, 75%; P = 0.58). The median cancer-free survival was also similar (P = 0.58); however, gastric wall recurrence was only encountered in the patients with EUS-FNA (n = 2). CONCLUSION: Preoperative EUS-FNA is not associated with increased risks of cancer-specific or overall survival. However, clinicians must consider the potential risks of needle tract seeding, and care should be taken when selecting patients.

Lipid Indexes and Quality Evaluation of Omega-3 Rich Oil from the Waste of Japanese Spanish Mackerel Extracted by Supercritical CO2.

Japanese Spanish mackerel (JSM) (Scomberomorus niphonius) is a marine fish species containing health-beneficial polyunsaturated fatty acids (PUFAs). In the present study, the quality of JSM by-products oils extracted by supercritical CO2 (SC-CO2) and organic solvent extraction was compared in terms of physico-chemical properties of the oils. Eicosapentaenoic acid (EPA) is one of the important polyunsaturated fatty acids present in SC-CO2-extracted skin and muscle oil 5.81 ± 0.69% and 4.93 ± 0.06%, respectively. The amount of docosahexaenoic acid (DHA) in SC-CO2-extracted skin and muscle oil was 12.56 ± 0.38% and 15.01 ± 0.28%, respectively. EPA and DHA are considered as important PUFAs for the development of brain function and the prevention of coronary heart diseases. Extracted oils showed considerable antioxidant activity. In the obtained oils, atherogenic index (AI) values varied from 0.72 to 0.93 and thrombogenic index (TI) ranged from 0.75 to 0.92, which is considered an acceptable level. Fatty acid composition, bio potentiality, thermogravimetric, and vitamin D analysis showed that oils extracted from JSM by-products can be a good source of oil for application in food, pharmaceutical and cosmetic industries. Therefore, the present research revealed the potentiality of green valorisation of S. niphonius by-products as a possible sustainable approach for targeting the era of zero waste.

Subcritical Water Hydrolysis of Comb Pen Shell (Atrina pectinata) Edible Parts to Produce High-Value Amino Acid Products.

Artina pectinata (Comb pen shell, CPS) is a high-protein source that contains a variety of essential amino acids. Subcritical water hydrolysis (SWH) was used to recover amino acids from the posterior adductor muscle (PAM), anterior adductor muscle (ADM), and mantle. The temperatures ranged from 120 °C to 200 °C, and the pressure and time of hydrolysis were 3 MPa and 30 min, respectively. Further characterization of the hydrolysates was performed to ascertain amino acid profiles and biofunctional properties. The hydrolysates contained more free amino acids than the untreated samples. Antioxidant activity of treated samples increased as SW temperatures increased. At 200 °C, those inhibiting ACE had a maximum antihypertensive activity of 200 °C in 1% PAM, ADM, and mantle with 85.85 ± 0.67, 84.55 ± 0.18, and 82.15 ± 0.85%, respectively, compared to 97.57 ± 0.67% in 1% standard captopril. Perhaps the most significant finding was the predominance of taurine in the three parts following SW treatment at 120 °C. The hydrolysates may be of considerable interest for use in food or energy drinks. SWH demonstrates efficacy in recovering amino acids, particularly taurine, from edible parts of A. pectinata.

Laser ablation of pancreatic cancer using a cylindrical light diffuser.

Pancreatic cancer (PC) is a leading cause of cancer death and its incidence and mortality have shown an increasing trend. Despite improvements in outcomes, another treatment option is required for PC. Laser ablation (LA) has been evaluated for the treatment of various types of cancer. The aim of this study was to assess the safety and feasibility of a novel cylindrical light diffuser in a xenograft model of PC. This study was performed using a customized high-power laser system. PANC-1 cells and BALB/c mice were used for experiments at a laser power of 5 W for 40 to 200 s at five different energy levels (n = 30). There was no acute bleeding or major complication. Using the cylindrical light diffuser, tumors were irradiated with similar size in each energy group. A correlation between laser dose and tumor necrosis was observed. Pearson's correlation for the relation between the amount of necrosis area and laser ablation energy on day 3 was 0.78 (p < 0.01). No statistical difference of necrosis area was exhibited when the necrosis area of each harvested tumor analyzed by dividing into 5 specimens for each energy. The study demonstrates that LA treatment using a cylindrical light diffuser induced remarkable tumor necrosis at histopathologic examinations. Laser ablation dosage and tumor response were strongly correlated, and the ablation procedure resulted in homogeneous tissue necrosis. No adverse event was encountered. These findings suggest that the devised cylindrical light diffuser offers a safe and effective means of treating pancreatic cancer.

Efficacy of a novel hemostatic adhesive powder in patients with upper gastrointestinal tumor bleeding.

BACKGROUND: Gastrointestinal tumor bleeding remains a clinical challenge because it is difficult to treat with conventional endoscopic hemostatic options. Recently, an endoscopic hemostatic powder (UI-EWD) was developed and reported to provide effective control of upper gastrointestinal bleeding. The aim of current study was to evaluate the feasibility and efficacy of this novel hemostatic powder in tumor bleeding. METHODS: A total of 41 consecutive patients with upper gastrointestinal tumor bleeding were included. UI-EWD was applied in all patients as an auxiliary hemostatic method as a salvage therapy or monotherapy during endoscopic treatment. Hemostasis success rates, adverse event related to UI-EWD, and rates of re-bleeding were evaluated. RESULTS: In all cases, UI-EWD application was successful at tumor bleeding sites. Immediate hemostasis occurred in 40/41 (97.5%) patients, and re-bleeding within 28 days occurred in 10 of 40 (22.5%) patients that achieved initial hemostasis. The success rate of immediate hemostasis for UI-EWD monotherapy was 100% (23/23). The re-bleeding rate at 28 days after UI-EWD monotherapy was 26.1% (6/23). No adverse events associated with UI-EWD application were encountered. CONCLUSIONS: The success rate of UI-EWD for immediate hemostasis in cases of GI tumor bleeding was excellent and UI-EWD produced promising results with respect to the prevention of re-bleeding. Based on these results, we suggest that UI-EWD be considered an effective salvage therapy or even monotherapy for GI tumor bleeding.

Can prophylactic argon plasma coagulation reduce delayed post-papillectomy bleeding? A prospective multicenter trial.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed post-papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy. METHODS: In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow-up duodenoscopy to identify post-papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post-papillectomy bleeding rate and the tumor persistence rate. RESULTS: The delayed post-papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non-APC group (P = 0.434). The post-procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure-related mortalities or serious complications. CONCLUSION: Prophylactic APC may not be effective in reducing delayed post-papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration-cris.nih.go.kr; KCT0001955).