Search Results (205)

A new lift enhancement scheme is designed for the cruise flight process of a tail-sitter UAV (Unmanned Aerial Vehicle), proposing a fusion configuration with embedded grid channels on the duct wall. The low pressure zone at the lip of the duct is induced to expand through the grid channels, forming a significant force component difference with the non-grid side, thereby generating significant lift effects for the propeller of the ducted fan during level flight. Taking a ducted fan system as an example, a design method for embedding grids into the ducted wall is established. By using the sliding mesh technique to simulate propeller rotation, the effects of annular distribution angle, grid channel width, circumferential and flow direction grid quantity on its aerodynamic performance are evaluated. The results indicate that the ducted fan embedded in the grid can generate a lift about 22.16% of total thrust without significantly affecting thrust and power characteristics. The increase in circumferential distribution angle increases within a reasonable range and benefits the lift of the propeller. However, the larger the grid width, the more it affects the lip and tail of the duct. Ultimately, the overall effect actually deteriorates the performance. The number of circumferential grids has a relatively small impact. As the number of flow grids increases, the aerodynamic characteristics of the entire fusion configuration significantly improves, due to its favorable induction of airflow at the lip and tail of the duct, as well as blocking the dissipation of blade-tip vortices. Full article

Breast cancer invasion and subsequent metastasis to distant tissues occur when cancer cells lose cell–cell contact, develop a migrating phenotype, and invade the basement membrane (BM) and the extracellular matrix (ECM) to penetrate blood and lymphatic vessels. The identification of the mechanisms which induce the development from a ductal carcinoma in situ (DCIS) to a minimally invasive breast carcinoma (MIBC) is an emerging area of research in understanding tumor invasion and metastatic potential. To investigate the progression from DCIS to MIBC, we analyzed peritumoral collagen architecture using correlative scanning electron microscopy (SEM) on histological sections from human biopsies. In DCIS, the peritumoral collagen organizes into concentric lamellae (‘circular fibers’) parallel to the ducts. Within each lamella, type I collagen fibrils align in parallel, while neighboring lamellae show orthogonal fiber orientation. The concentric lamellar arrangement of collagen may physically constrain cancer cell migration, explaining the lack of visible tumor cell invasion into the peritumoral ECM in DCIS. A lamellar dissociation or the development of small inter fiber gaps allowed isolated breast cancer cell invasion and exosomes infiltration in the DCIS microenvironment. The radially arranged fibers observed in the peri-tumoral microenvironment of MIBC biopsies develop from a bending of the circular fibers of DCIS and drive a collective cancer cell invasion associated with an intense immune cell infiltrate. Type I collagen fibrils represent the peri-tumoral nano-environment which can play a mechanical role in regulating the development from DCIS to MIBC. Collectively, it is plausible to suggest that the ECM effectors implicated in breast cancer progression released by the interplay between cancer, stromal, and/or immune cells, and degrading inter fiber/fibril hydrophilic ECM components of the peritumoral ECM, may serve as key players in promoting the dissociation of the concentric collagen lamellae. Full article

Clinical mastitis in small ruminants is usually seen with an incidence of less than 5% and most cases, especially with hyperacute evolution, are not referred for hospital care. During the 5-year survey, 16 goats and 7 sheep, totaling 23 small ruminants, met the inclusion criteria with a definitive diagnosis of clinical mastitis. Clinical signs ranged greatly among cases, varying from septic state in hyperacute cases, and enlarged, pendulous udder associated with chronic pain and abnormal gait in chronic cases. Microbiological culture revealed a wide array of bacterial pathogens, including Staphylococcus aureus, Escherichia coli, Streptococcus spp., and Pasteurella spp. In vitro antimicrobial susceptibility profiles varied greatly among bacteria isolates, ranging from sensitive to all tested antimicrobials to a multi-resistant profile. Pathological features included hyperemia and dark red areas of necrosis in the skin, marked hyperemia of the affected gland at the cut surface, lactiferous ducts and gland cisterns filled by cloudy or suppurative fluid, abscesses, and hardness of the mammary gland parenchyma. This retrospective study highlights the multifactorial nature and clinical variability of mastitis in small ruminants, demonstrating its significant impact on animal health, welfare, and production. Full article

Background/Objectives: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small- and large-duct types. Small-duct-type iCCAs are associated with a better prognosis, and each subclassification requires different surgical strategies. The efficacy of chemotherapy, including immune checkpoint inhibitors, may vary between subclassifications. However, there are no reports on tumor immune microenvironment (TIME) analyses based on iCCA subclassifications. This study investigated subclassification-specific TIMEs in iCCAs for the purpose of establishing appropriate pharmacotherapy. Methods: A total of 131 resected iCCA cases were analyzed, comprising 73 tumors classified as small-duct-type and 58 as large-duct-type based on pathological evaluation. Immunohistochemical analyses targeting CD8, PD-1, PD-L1, CTLA-4, and S100 protein (a dendritic cell [DC] marker) were performed to investigate the immune-cell status in each subclassification. Results: Large-duct-type iCCA had a significantly higher CD8 expression in tumor-infiltrating cells than small-duct-type ICC. However, the expression of other molecules did not significantly differ between the two tumor types. The proportion of tumors with a high level of S100 protein expression (DC-high group) in tumor-infiltrating cells was significantly higher in small-duct-type ICCs than in large-duct-type iCCAs (30% vs. 1.7%). In small-duct-type iCCAs, the expression levels of CD8, PD-1, PD-L1, and CTLA-4 were significantly higher in the DC-high group than in the DC-low group. Conclusions: We revealed subclassification-specific TIMEs in iCCAs. A subset of small-duct-type iCCAs exhibited strong DC infiltration. In these patients, the tumors may establish an immunosuppressive TIME to evade antitumor immunity triggered by DC-mediated antigen presentation. These findings may contribute to the development of tailored pharmacotherapy for each iCCA subclassification. Full article

Background: Infections of the biliary tract are found frequently in pathologically or surgically altered bile ducts. Mostly these infections result from the ascent of bacteria or fungi from the small bowel, although hematogeneous infections of the biliary system may also occur. The biliary sphincter and the continuous flow of bile are thought to prevent or limit ascending infections. Obstructive alterations in the biliary system are the most frequent indication of endoscopic retrograde cholangiography (ERC). The aim of this study was to analyze the spectrum and frequency of microbes within the bile, and discover the influence of earlier sphincterotomy. Methods: In our department, we routinely aspirate bile for microbiologic culture during ERC. For this study, all ERC performed in 2014–2018 were retrospectively analyzed, including all microbiological reports. Indications for the endoscopic examination were also recorded. In addition, the findings were correlated with whether or not a sphincterotomy had been previously performed, and whether or not there had been antibiotic treatment prior to the examination. Results: A total of 2253 successful standard ERC procedures were performed between 2014 and 2016. In 486 cases, bile was aspirated and sent for microbiologic culture. In total, 1220 bile samples were analyzed, and bacteria or fungi were found in 1029 (86.0%). Enterococci and Enterobacter were found most commonly, but E. coli, streptococci, klebsiella, and staphylococci were also found. In 11.2% of positive cultures, multiresistant pathogens were identified. In up to 29% Candida spp., most commonly, Candida albicans (68%) were also found, either alone or in conjunction with bacteria. Neither prior sphincterotomy nor the use of peri-interventional antibiotics had a major influence on the frequency with which positive bile cultures were detected. Conclusions: Aspiration of bile during ERC is of high clinical relevance, because microbiological analysis reveals the frequent presence of bacteria and fungi, knowledge of which may be useful for deciding on anti-infective treatment. Full article

Background/Objectives: Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. Although these subclassifications may help determine the appropriate treatment strategy, subclassification diagnosis currently depends on postoperative pathological examinations. This study aimed to establish a nomogram to predict ICC subclassifications. Methods: This study included 126 patients with ICC who underwent liver resection. The participants were divided into small and large duct-type ICC groups. A nomogram to predict large duct-type ICC was developed using four diagnostic imaging findings: rim-type enhancement in the early phase, an absence of tumor enhancement in the early phase, the presence of peripheral biliary dilatation due to tumor invasion, the presence of penetrating Glisson’s vessels in the tumor, and two laboratory test results: serum gamma-glutamyl transpeptidase and carbohydrate antigen 19-9 levels. Nomogram performance was also assessed. Moreover, the bootstrap method and calibration plots were used to assess nomogram validity. Results: Seventy and fifty-six patients were pathologically diagnosed with small and large duct-type ICCs, respectively. The area under the curve of the established nomogram was 0.93 and remained 0.91 after Harrell’s bias correction. The sensitivity and specificity of the nomogram developed using the Youden index were higher than those of any of the characteristic imaging findings. Calibration plots demonstrated a strong association between the nomogram and the actual data. Conclusions: We developed a novel preoperative nomogram to predict large duct-type ICC. This nomogram can be clinically useful for predicting the subclassifications of ICCs and may contribute to the establishment of a more appropriate treatment strategy for ICC. Full article

Background: Synchronous small- and large-duct intrahepatic cholangiocarcinoma (iCCA) represents a rare and heterogeneous entity, posing challenges for diagnosis, prognosis, and treatment selection. The pathological and molecular diversity between these subtypes influences tumor behavior and therapeutic response, necessitating a personalized approach. This study investigates the molecular and pathological heterogeneity of synchronous iCCA and its clinical implications. Methods: This prospective case series included six patients diagnosed with synchronous small- and large-duct iCCA at the Military Medical Academy, Sofia, between January 2023 and January 2025, with a median follow-up of 15 months. Tumor classification was based on histopathological examination, immunohistochemical analysis, and next-generation sequencing (NGS)-based genomic profiling. Radiological and clinical data were analyzed to assess tumor growth patterns, treatment response, and progression-free survival (PFS). Results: Small-duct-predominant iCCA was associated with IDH1/2 mutations and FGFR2 fusions, a mass-forming growth pattern, and longer PFS. In contrast, large-duct-predominant iCCA exhibited KRAS, TP53, and NF1 mutations, an infiltrative periductal growth pattern, and a more aggressive clinical course with shorter PFS. Tumor mutational burden-high (TMB-H) and microsatellite instability-high (MSI-H) were observed in a subset of large-duct iCCA cases, suggesting potential benefit from immune checkpoint inhibitors (ICIs). Conclusions: Synchronous small- and large-duct iCCA demonstrates distinct molecular, histopathological, and clinical features, necessitating individualized treatment strategies. Targeted therapies for IDH1/2- and FGFR2-altered small-duct iCCA have shown efficacy, whereas large-duct iCCA remains more aggressive and treatment-resistant, requiring novel therapeutic approaches. Future research should focus on adaptive treatment strategies that account for tumor heterogeneity and dominant molecular drivers. Full article

Background: Glucagon-like peptide-2 (GLP-2) is a gut hormone secreted in response to nutrient intake and regulates lipid metabolism in the gut. The present study aims to elucidate the underlying mechanism of GLP-2 in stimulating gut lipid secretion in the fasted state by testing whether GLP-2 signals through the brain’s GLP-2 receptor and melanocortin 4 receptor (MC4R). Methods: Sprague-Dawley rats were implanted with a mesenteric lymph duct cannula for measuring gut lipid secretion and an intracerebroventricular cannula for infusion of a GLP-2R antagonist (GLP-2(11-33)), an MC4R antagonist (SHU9119), or saline as a control. The rat received a lipid infusion into the small intestine and a peritoneal injection of GLP-2 five hours later. Results: Brain administration of a GLP-2R antagonist or an MC4R antagonist attenuated the stimulatory effects of peripheral GLP-2 on lymph triglyceride output. These effects were associated with differential changes in the expression of key genes in jejunal endothelial cells, smooth muscle cells, and neuronal cells. Conclusions: These results support the involvement of central GLP-2R and MC4R in a neural pathway for GLP-2 to mobilize lipids stored in the gut during the post-absorptive state. Full article

Distributed propulsion systems are strategically placed along the aircraft wingspan to ingest the fuselage boundary layer, thereby enhancing propulsion efficiency. However, the aerodynamic effects of S-shaped duct geometry on a distributed propulsion system are not fully understood. The impact of the S-shaped duct inlet aspect ratio and centerline offset on the inlet distortion of ducted fans was numerically investigated using a method based on the circumferential body force model. The results show that the most severe inlet distortion occurs when a large centerline offset is combined with a small aspect ratio. For an S-shaped duct with a substantial centerline offset, increasing the aspect ratio mitigates the distortion level in the edge fans. Specifically, increasing the aspect ratio from 6 to 10 reduces the total pressure and swirl distortion index in the edge fan by up to 80.1% and 84.2%, respectively. In an S-shaped duct with a small aspect ratio, decreasing the centerline offset from 1.75 times to 0.75 times the ducted fan diameter lowers the total pressure and swirl distortion index in the edge fan by up to 75.2% and 87.5%, respectively. These insights provide valuable information for the integrated design and optimization of the S-shaped duct in distributed propulsion systems. Full article

Based on the Daozhen–Wulong Zimuyan tunnel, the distance from the outlet of the air duct to the tunnel face and the diameter of the air duct are studied through an orthogonal experimental design. Aiming at the influence of the position of the air duct of the axial flow fan in the tunnel on the ventilation flow field, the improved TOPSIS theory is adopted for detailed data analysis, and the flow field characteristics are thoroughly checked to identify the optimal working condition configuration. The results show that with the increase in the distance between the air duct and the tunnel face, the local CO concentration will first decrease and then increase, indicating that too large or too small a distance will weaken the effective CO emission ability of the tunnel face, and the distance between the air duct outlet and the tunnel face is the best scheme; by combining the TOPSIS theory, entropy weight method, and analytic hierarchy process, the optimization scheme is obtained. When the distance between the outlet of the air duct and the working face is 15 m, the side wall of the air duct is 4 m away from the air, the diameter of the air duct is 1.8 m, the flow field in the tunnel shows a high degree of stability, the wind speed is significantly increased, and the vortex area that may hinder the air flow is effectively eliminated. The ventilation efficiency is greatly improved and the overall stability of the tunnel is enhanced. Full article

Extracellular vesicles (EVs) contain bioactive lipids that play a key role in pathophysiology. We hypothesized that EVs released from salt-loaded hypertensive diabetic db/db mice have increased bioactive lipid content that inhibits intracellular calcium mobilization and increases the activity of renal epithelial sodium channels (ENaC). An enrichment of sphingomyelins (SMs) was found in small urinary EVs (uEVs) isolated from salt-loaded hypertensive diabetic db/db mice (n = 4) compared to non-salt loaded db/db mice with diabetes alone (n = 4). Both groups of mice were included in the same cohort to control for variability. Cultured mouse cortical collecting duct (mpkCCD) cells loaded with a calcium reporter dye and challenged with small uEVs from hypertensive diabetic db/db mice showed a decrease in calcium mobilization when compared to cells treated with small uEVs from diabetic db/db mice. The amiloride-sensitive transepithelial current was increased in mpkCCD cells treated with small uEVs with abundant sphingomyelin content from hypertensive diabetic db/db mice in a dose- and time-dependent manner. Similar results were observed in mpkCCD cells and Xenopus 2F3 cells treated with exogenous sphingomyelin in a time-dependent manner. Single-channel patch clamp studies showed a decrease in ENaC activity in cells transiently transfected with sphingomyelin synthase 1/2 specific siRNA compared to non-targeting siRNA. These data suggest EVs with high sphingomyelin content positively regulate renal ENaC activity in a mechanism involving an inhibition of calcium mobilization. Full article

The missions of modern aircraft require multiple abilities, such as highly efficient taking-off and landing, fast arrival, and long-endurance hovering. It is difficult to achieve all technical objectives using traditional aircraft design technology. The active flow control technology using the concept of a co-flow jet (CFJ) is a flow control method without a mass source that does not require air from the engine. It has strong flow control ability in low-speed flow, can greatly improve the stall angle of the aircraft, and can obtain large lift enhancement. At transonic conditions, it can lead to a larger lift–drag ratio with a small expense. CFJ technology has great application potential for aircraft due to its flexible control strategy and remarkable control effect. In this paper, the concept of a combination of CFJ and variable camber technology is proposed which realizes the change of airfoil camber to meet different task requirements with the movable droop head. By using the built-in ducted fan, air is blown and sucked in the jet channel so as to realize CFJ flow control. In a state of high-speed flight, complete geometric restoration is achieved by closing the channel and retracting the droop head. In this paper, the design and aerodynamic analysis of a CFJ device with variable camber based on a supercritical airfoil with small camber and a small leading-edge radius are carried out using the computational fluid dynamics (CFD) method. Comparative studies are conducted for different schemes on the taking off and landing performances, and discussions are had on core technical parameters such as power consumption. The results indicate that by utilizing the CFJ technology with more than 10 degrees of droop device, the maximum lift coefficient of a supercritical airfoil with a small camber and leading-edge radius, which is suitable for transonic flight, can be increased to a value larger than 4.0. Full article

A 30-year-old woman presented with progressive edema and mild diarrhea. Laboratory examination revealed hypoalbuminemia. She underwent ^99mTc-antimony sulphide colloid (^99mTc-ASC) lymphoscintigraphy to evaluate potential loss of protein through gastrointestinal tract caused by lymphatic leakage and detect abnormalities in the lymphatic systems. The images showed abnormal leakage of radiotracers in the bowel, suggestive of protein loss through the gastrointestinal tract. Abnormal visualization of the lower part of thoracic duct and bilateral venous angle was also demonstrated on ^99mTc-ASC scintigraphy. It suggested secondary intestinal lymphangiectasis caused by lymphatic obstruction and reflux. Enhanced CT reconstruction of the small intestine revealed roughness and thickening of intestinal wall, consistent with the diagnosis of protein-losing enteropathy. Full article

Background and Aims: Primary biliary cholangitis (PBC) leads to the slow, progressive destruction of the small bile ducts with consecutive cholestasis and intrahepatic cholangitis. If this disease remains untreated, liver parenchyma will be damaged resulting in fibrosis and end-stage liver disease with the need for transplantation. The approval of the Farnesoid X receptor agonist obeticholic acid (Ocaliva; OCA) in early 2017 expanded the drug therapy options of PBC, which previously consisted primarily of the administration of ursodeoxycholic acid (UDCA). Patients and Methods: Included in our prospective pilot study were 16 patients with a confirmed diagnosis of PBC who were treated with an add-on therapy with OCA (5 mg/d). None of the patients had an overlap to autoimmune hepatitis. Patients were investigated between 09/2022 and 09/2023. Results: The majority of patients was female (15/16, 93.75%), and the mean age was 57.63 ± 9.59 (43–77) years. OCA treatment led to a statistically significant decrease in aspartate aminotransferase (AST; AST baseline: 38.50 [26.25; 50.00] IU/L vs. AST 6-month follow-up: 23.50 [21.50; 44.25] IU/L, p = 0.0012), alanine aminotransferase (ALT; ALT baseline: 55.50 [28.75; 97.00] IU/L vs. ALT 6-month follow-up: 36.50 [28.00; 57.25] IU/L, p = 0.0035), and gamma-glutamyl transferase (GGT; GGT baseline: 168.00 [100.30; 328.50] IU/L vs. GGT 6-month follow-up: 88.00 [44.50; 259.80] IU/L, p = 0.0063), while the decrease in alkaline phosphatase (AP) was not statistically significant (AP baseline: 197.00 [170.00; 253.30] IU/L vs. AP 6-month follow-up: 196.00 [134.00; 227.00] IU/L, p = 0.0915). In addition, liver stiffness measurement (LSM) showed a statistically significant decrease after six months of treatment with OCA (LSM baseline: 7.85 [5.55; 10.13] kPa vs. LSM 6-month follow-up: 5.95 [4.55; 8.225] kPa, p = 0.0001). However, the increase in enzymatic liver function measured by LiMAx failed to reach statistical significance, but showed a positive trend (LiMAx baseline: 402.50 [341.50; 469.80] μg/kg/h vs. LiMAx 6-month follow-up: 452.50 [412.50; 562.00] μg/kg/h, p = 0.0625). In none of our patients did therapy with obeticholic acid have to be stopped due to pruritus or poor tolerability. Conclusions: In patients with PBC without adequate response to UDCA, OCA is a promising alternative, which in our group of 16 patients led to a significant improvement of liver enzymes, the amelioration of liver fibrosis, and an increase in liver function capacity in a short-term clinical course. Full article

Parasitic gastrointestinal worms (i.e., helminths) remain a significant global health and economic burden. The increasing inefficacy of current anthelmintic drugs against parasitic diseases necessitates the discovery of novel therapeutic options. This study investigated the anthelmintic properties and therapeutic potential of stonefish ichthyocrinotoxins (i.e., secreted skin toxins). xWORM (xCELLigence Worm Real-Time Motility Assay) was used to evaluate the anthelmintic activity of ichthyocrinotoxins from two stonefish species, Synanceia horrida (Estuarine Stonefish) and Synanceia verrucosa (Reef Stonefish), against the infective third-stage larvae of Nippostrongylus brasiliensis (Rodent Hookworm). Both toxins demonstrated potent anthelmintic effects, with S. horrida ichthyocrinotoxin exhibiting greater potency (IC₅₀ = 196.0 µg/mL) compared to ichthyocrinotoxin from S. verrucosa (IC₅₀ = 329.7 µg/mL). Fractionation revealed that the anthelmintic activity of S. verrucosa is likely driven by synergistic interactions between the large (>3 kDa) and small (<3 kDa) components. In contrast, the small components isolated from S. horrida ichthyocrinotoxin were responsible for the majority of the observed activity, making them a more attractive therapeutic candidate. Furthermore, despite the cytotoxicity of crude S. horrida ichthyocrinotoxin against human skin and bile duct cell lines, the isolated small components exhibited potent anthelmintic effects (IC₅₀ = 70.5 µg/mL) with negligible cytotoxicity (<10% decrease in survival at 100 µg/mL). While further research is necessary to fully characterise these compounds and assess their clinical suitability, this study highlights the potential of stonefish ichthyocrinotoxins as a novel source of anthelmintic therapeutics. Full article