Regulation of the AGEs-induced inflammatory response in human periodontal ligament cells via the AMPK/NF-κB/ NLRP3 signaling pathway.

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE). It showed that advanced glycation end products modulate inflammatory responses in HPDLCs by activating NLRP1 and NLRP3 inflammasomes, which are further regulated through the NF-κB signaling pathway. Furthermore, AGEs synergize with NOD2, NLRP1, and NLRP3 inflammasomes to augment MDP-induced inflammation significantly.

Entanglement-based quantum digital signatures over a deployed campus network.

The quantum digital signature protocol offers a replacement for most aspects of public-key digital signatures ubiquitous in today's digital world. A major advantage of a quantum-digital-signatures protocol is that it can have information-theoretic security, whereas public-key cryptography cannot. Here we demonstrate and characterize hardware to implement entanglement-based quantum digital signatures over our campus network. Over 25 hours, we collect measurements on our campus network, where we measure sufficiently low quantum bit error rates (<5% in most cases) which in principle enable quantum digital signatures at over 50 km as shown through rigorous simulation accompanied by a noise model developed specifically for our implementation. These results show quantum digital signatures can be successfully employed over deployed fiber. Moreover, our reported method provides great flexibility in the number of users, but with reduced entanglement rate per user. Finally, while the current implementation of our entanglement-based approach has a low signature rate, feasible upgrades would significantly increase the signature rate.

A novel histone deacetylase inhibitor Se-SAHA attenuates isoproterenol-induced heart failure via antioxidative stress and autophagy inhibition.

Heart failure is associated with histone deacetylase (HDAC) regulation of gene expression, the inhibition of which is thought to be beneficial for heart failure therapy. Here, we explored the cardioprotective effects and underlying mechanism of a novel selenium-containing HDAC inhibitor, Se-SAHA, on isoproterenol (ISO)-induced heart failure. We found that pretreatment with Se-SAHA attenuated ISO-induced cardiac hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Se-SAHA significantly attenuated the generation of ISO-induced reactive oxygen species (ROS) and restored the expression levels of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) in vitro. Furthermore, Se-SAHA pretreatment prevented the accumulation of autophagosomes. Se-SAHA reversed the high expression of HDAC1 and HDAC6 induced by ISO incubation. However, after the addition of the HDAC agonist, the effect of Se-SAHA on blocking autophagy was inhibited. Using ISO-induced mouse models, cardiac ventricular contractile dysfunction, hypertrophy, and fibrosis was reduced treated by Se-SAHA. In addition, Se-SAHA inhibited HDAC1 and HDAC6 overexpression in ISO-treated mice. Se-SAHA treatment significantly increased the activity of SOD2 and improved the ability to eliminate free radicals. Se-SAHA hindered the excessive levels of the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 in heart failure mice. Collectively, our results indicate that Se-SAHA exerts cardio-protection against ISO-induced heart failure via antioxidative stress and autophagy inhibition.

A Kalman Filtering Algorithm for Measurement Interruption Based on Polynomial Interpolation and Taylor Expansion.

Combined SINS/GPS navigation systems have been widely used. However, when the traditional combined SINS/GPS navigation system travels between tall buildings, in the shade of trees, or through tunnels, the GPS encounters frequent signal blocking, which leads to the interruption of GPS signals, and as a result, the combined SINS/GPS-based navigation method degenerates into a pure inertial guidance system, which will lead to the accumulation of navigation errors. In this paper, an adaptive Kalman filtering algorithm based on polynomial fitting and a Taylor expansion is proposed. Through the navigation information output from the inertial guidance system, the polynomial interpolation method is used to construct the velocity equation and position equation of the carrier, and then the Taylor expansion is used to construct the virtual measurement at the moment of the GPS signal interruption, which can make up for the impact of the lack of measurement information on the combined SINS/GPS navigation system when the GPS signal is interrupted. The results of computer simulation experiments and road measurement tests based on the loosely combined SINS/GPS navigation system show that when the carrier faces a GPS signal interruption situation, compared with a combined SINS/GPS navigation algorithm that does not take any rescue measures, our proposed combined SINS/GPS navigation algorithm possesses a higher accuracy in the attitude angle estimation, a higher accuracy in the velocity estimation, and a higher accuracy in the positional localization, and the system possesses higher stability.

DNA-Conjugated Cyclopropane Derivatives Constructed from Sulfonium Ylides with α,ß-Unsaturated Ketones.

Here, we report a DNA-compatible reaction for the generation of cyclopropane derivatives using thiolides with α,ß-unsaturated ketones in the absence of transition metal and N2 protection, which is convenient for DNA encoded library (DEL) construction. This approach allows the rapid and efficient production of a series of DEL libraries of potentially biologically active cyclopropanes and spirocyclopropyl oxindole derivatives.

Bayesian homodyne and heterodyne tomography: erratum.

We correct typographical errors in Eq. (15) in [Opt. Express30, 15184 (2022)10.1364/OE.456597] [1]. These errors were not present in the actual formulas used to calculate the results of the paper, so all results remain unaffected.

Fully Passive Quantum Key Distribution.

We propose a fully passive linear optical quantum key distribution (QKD) source that implements both random decoy-state and encoding choices with postselection only, thus eliminating all side channels in active modulators. Our source is general purpose and can be used in, e.g., BB84, the six-state protocol, and reference-frame-independent QKD. It can even potentially be combined with measurement-device-independent QKD to achieve robustness against side channels in both detectors and modulators. We also perform a proof-of-principle experimental source characterization to show its feasibility.

Unravelling the Hepatic Elimination Mechanisms of Colistin.

PURPOSE: Colistin is an antibiotic which is increasingly used as a last-resort therapy in critically-ill patients with multidrug resistant Gram-negative infections. The purpose of this study was to evaluate the mechanisms underlying colistin's pharmacokinetic (PK) behavior and to characterize its hepatic metabolism. METHODS: In vitro incubations were performed using colistin sulfate with rat liver microsomes (RLM) and with rat and human hepatocytes (RH and HH) in suspension. The uptake of colistin in RH/HH and thefraction of unbound colistin in HH (fu,hep) was determined. In vitro to in vivo extrapolation (IVIVE) was employed to predict the hepatic clearance (CLh) of colistin. RESULTS: Slow metabolism was detected in RH/HH, with intrinsic clearance (CLint) values of 9.34± 0.50 and 3.25 ± 0.27 mL/min/kg, respectively. Assuming the well-stirred model for hepatic drug elimination, the predicted rat CLh was 3.64± 0.22 mL/min/kg which could explain almost 70% of the reported non-renal in vivo clearance. The predicted human CLh was 91.5 ± 8.83 mL/min, which was within two-fold of the reported plasma clearance in healthy volunteers. When colistin was incubated together with the multidrug resistance-associated protein (MRP/Mrp) inhibitor benzbromarone, the intracellular accumulation of colistin in RH/HH increased significantly. CONCLUSION: These findings indicate the major role of hepatic metabolism in the non-renal clearance of colistin, while MRP/Mrp-mediated efflux is involved in the hepatic disposition of colistin. Our data provide detailed quantitative insights into the hereto unknown mechanisms responsible for non-renal elimination of colistin.

Bimodal persistent luminescence for autofluorescence-free ratiometric biosensing.

In optical biosensing, analyte-independent factors such as autofluorescence interference and excitation source fluctuation decrease the sensitivity and accuracy. Herein, we reported a bimodal persistent luminescence strategy to design dual-emissive persistent luminescence nanoparticles (PLNPs) with built-in self-calibration to preclude interference from analyte-independent factors in biosensing. As a proof of concept, ZnGa2O4:Cr PLNPs with emissions at both 490 nm and 695 nm were designed. The I490/I695 ratio of ZnGa2O4:Cr was readily adjusted by simply changing the doping concentration of Cr3+. The ZnGa2O4:Cr PLNPs were employed for the ratiometric detection of urinary mesna. A good linear relationship between the I490/I695 ratio of ZnGa2O4:Cr-based nanoprobe and the concentration of mesna was obtained in the range of 0-40 µM. The limit of detection was about 0.40 µM. Results showed that autofluorescence interference from urine was totally eliminated by collecting the persistent luminescence signal of ZnGa2O4:Cr after excitation ceased. Moreover, the built-in self-calibration feature of the ratiometric ZnGa2O4:Cr PLNPs efficiently suppressed the interference from fluctuations in instrumental parameters during urinary mesna detection. The recovery rates of mesna in the spiked urine samples are in the range of 99.1~109.0%, showing the reliability of the ratiometric ZnGa2O4:Cr PLNPs in urinary mesna detection. ZnGa2O4:Cr can further be expanded to the detection of other analytes in complex matrices. This study may open new opportunities for the design of dual-emissive PLNPs with tunable ratios of emission intensity, and it can further promote the applications of optical biosensing in disease diagnosis, food safety, and environmental monitoring.

Diagnostic accuracy of updated risk assessment criteria and development of novel computational prediction models for patients with suspected choledocholithiasis.

BACKGROUND: There are risks of choledocholithiasis in symptomatic gallstones, and some surgeons have proposed the identification of choledocholithiasis before cholecystectomy. Our goal was to evaluate the diagnostic accuracy of the latest guidelines and create computational prediction models for the accurate prediction of choledocholithiasis. METHODS: We retrospectively reviewed symptomatic gallstone patients hospitalized with suspected choledocholithiasis. The diagnostic performance of 2019 and 2010 guidelines of the American Society for Gastrointestinal Endoscopy (ASGE) and 2019 guideline of the European Society of Gastrointestinal Endoscopy (ESGE) in different risks. Lastly, we developed novel prediction models based on the preoperative predictors. RESULTS: A total of 1199 patients were identified and 681 (56.8%) had concurrent choledocholithiasis and were included in the analysis. The specificity of the 2019 ASGE, 2010 ASGE, and 2019 ESGE high-risk criteria was 85.91%, 72.2%, and 88.42%, respectively, and their positive predictive values were 85.5%, 77.4%, and 87.3%, respectively. For Mid-risk patients who followed 2019 ASGE about 61.8% of them did not have CBD stones in our study. On the choice of surgical procedure, laparoscopic cholecystectomy + laparoscopic transcystic common bile duct exploration can be considered the optimal treatment choice for cholecysto-choledocholithiasis instead of Endoscopic Retrograde Cholangio-Pancreatography (ERCP). We build seven machine learning models and an AI diagnosis prediction model (ModelArts). The area under the receiver operating curve of the machine learning models was from 0.77 to 0.81. ModelArts AI model showed predictive accuracy of 0.97, recall of 0.97, precision of 0.971, and F1 score of 0.97, surpassing any other available methods. CONCLUSION: The 2019 ASGE guideline and 2019 ESGE guideline have demonstrated higher specificity and positive predictive value for high-risk criteria compared to the 2010 ASGE guideline. The excellent diagnostic performance of the new artificial intelligence prediction model may make it a better choice than traditional guidelines for managing patients with suspected choledocholithiasis in future.

Qingyi granules ameliorate severe acute pancreatitis in rats by modulating the gut microbiota and serum metabolic aberrations.

CONTEXT: Qingyi granules can be used to effectively treat patients with severe acute pancreatitis (SAP). OBJECTIVE: To elucidate the role of gut microbiota-mediated metabolism in the therapeutic effects of Qingyi granules. MATERIALS AND METHODS: Sprague-Dawley rats were grouped into the sham operation, SAP model, Qingyi granule intervention (Q, 1.8 g/kg) and emodin intervention (E, 50 mg/kg) groups and observed for 24 h. H&E staining and ELISA were used for histopathological analysis and serum enzyme and cytokine assays. 16S rDNA sequencing and UHPLC-HRMS were used for gut microbiota analysis and untargeted metabolomics. RESULTS: In SAP rats, Qingyi granules decreased the pancreatic pathological score (Q, 7.4 ± 1.14; SAP, 11.6 ± 1.14, p < 0.01); serum amylase (Q, 121.2 ± 6.7; SAP, 144.3 ± 8.86, p < 0.05), lipase (Q, 566 ± 20.34; SAP, 656.7 ± 29.32, p < 0.01), and diamineoxidase (Q, 492.8 ± 26.08; SAP, 566.1 ± 26.83, p < 0.05) activities; and IL-1ß (Q, 29.48 ± 0.88; SAP, 36.17 ± 1.88, p < 0.01), IL-6 (Q, 112.2 ± 3.57; SAP, 128.9 ± 9.09, p < 0.05) and TNF-α (Q, 215.3 ± 8.67; SAP, 266.4 ± 28.03, p < 0.05) levels. SAP induced Helicobacter and Lactobacillus overgrowth and suppressed Romboutsia and Allobaculum growth and caused aberrations in bacterial metabolites, which were partly reversed by Qingyi granules. DISCUSSION AND CONCLUSIONS: Qingyi granules can modulate the gut microbiota and metabolic abnormalities to ameliorate SAP. Multi-omics approaches allow systematic study of the pharmacological mechanisms of compound prescriptions for critical illnesses.

CHI3L1 predicted in malignant entities is associated with glioblastoma immune microenvironment.

Effective immunotherapies for patients with glioblastoma (GBM) are urgently needed. Chitinase-3 like-protein-1 (CHI3L1) play important roles in the development of gliomas. However, its role in glioma-related immune responses remains unclear. We aimed to comprehensively investigate its biological features and clinical value in glioma, especially in GBM. Transcriptome, proteome and single-cell RNA-sequencing databases were enrolled in the study. Immunostaining and immunoblotting were performed for validation. CHI3L1 was highly correlated with clinical and molecular features, suggesting that high CHI3L1 expression is more likely to be predicted as malignant entities. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed CHI3L1 closely associated with immune responses and inflammatory activities in GBM. In addition, CHI3L1 also correlated with immune cell infiltration and immune checkpoints. Our study suggests that inhibition of CHI3L1 may help to reduce immunosuppression and overcome immunotherapy resistance, which would be an therapeutic area for the treatment of GBM.

Bayesian homodyne and heterodyne tomography.

Continuous-variable (CV) photonic states are of increasing interest in quantum information science, bolstered by features such as deterministic resource state generation and error correction via bosonic codes. Data-efficient characterization methods will prove critical in the fine-tuning and maturation of such CV quantum technology. Although Bayesian inference offers appealing properties-including uncertainty quantification and optimality in mean-squared error-Bayesian methods have yet to be demonstrated for the tomography of arbitrary CV states. Here we introduce a complete Bayesian quantum state tomography workflow capable of inferring generic CV states measured by homodyne or heterodyne detection, with no assumption of Gaussianity. As examples, we demonstrate our approach on experimental coherent, thermal, and cat state data, obtaining excellent agreement between our Bayesian estimates and theoretical predictions. Our approach lays the groundwork for Bayesian estimation of highly complex CV quantum states in emerging quantum photonic platforms, such as quantum communications networks and sensors.

Mechanically Tough and Regenerable Antibacterial Nanofibrillated Cellulose-Based Aerogels for Oil/Water Separation.

Nanofibrillated cellulose (NFC)-based aerogels have been widely used for various applications. However, the disadvantages of poor structural stability, low mechanical toughness, and easy contamination by bacteria hinder their large-scale application. In this work, 3-(3'-acrylicacidpropylester)-5,5-dimethyl hydantoin (APDMH) was grafted on oxidized NFC (ONC) to prepare antibacterial poly(APDMH)-g-ONC (PAC). PAC and poly(ethyleneimine) (PEI) were chemically cross-linked using 3-glycidoxypropyltrimethox (GPTMS), aiming at constructing a PAC-g-PEI aerogel with multiple network structures. The mechanical behaviors of composite aerogel and oil/water separation performances under different conditions were investigated. PAC-g-PEI aerogel exhibits outstanding fatigue resistance (>50 cycles of compression) and superior elasticity (96.76% height recovery after five compression-release cycles at 50% strain). The obtained superhydrophilic and underwater-oleophobic properties endow the aerogel with excellent oil/water separation performances, achieving a satisfactory separation efficiency of over 99% and flux of over 9500 L·m-2·h-1. Furthermore, the chlorinated aerogel of PAC-g-PEI-Cl shows highly efficient and rechargeable antibacterial properties, can inactivate 6.72-log Escherichia coli and 6.60-log Staphylococcus aureus within 10 min, and can still kill all inoculated bacteria after 50 cycles. In addition, PAC-g-PEI-Cl aerogel can inhibit biofilm formation, making it a promising candidate for highly efficient oil/water separation applications in diverse harsh conditions.

Plaque progression at coronary CT angiography links non-alcoholic fatty liver disease and cardiovascular events: a prospective single-center study.

OBJECTIVES: The presence of non-alcoholic fatty liver disease (NAFLD) has been associated with major adverse cardiovascular events (MACEs); however, the mechanisms that initiate the risk for MACEs in patients with NAFLD remain unknown. We sought to investigate whether plaque progression (PP), determined by coronary CT angiography (CCTA), moderate the relationship between NAFLD and MACEs. METHODS: A total of 1683 asymptomatic participants (mean age, 63.3 ± 9.4 [range, 38-85] years; 1117 men) who underwent baseline and follow-up CCTA examination were prospectively included in our study. All of the participants were divided into the NAFLD and non-NAFLD groups. PP was determined by follow-up CCTA. The primary endpoint was MACEs, defined as the composite of all-cause death, nonfatal myocardial infarction, and unplanned hospitalization for acute coronary syndrome leading to revascularization. RESULTS: At follow-up CCTA, participants with NAFLD showed higher incidence of PP than those without [33.0% (248/752) vs. 16.6% (155/931), p < 0.001]. Compared with non-NAFLD participants, participants with NAFLD had a lower 9.7-year event-free survival rate (80.9 vs. 66.4%, log-rank p < 0.001). Cox regression analysis revealed NAFLD was significantly associated with MACEs (HR = 1.63, 95% CI: 1.28 to 2.06, p < 0.001) after adjusting for covariables. However, this association was no longer significant after adjustment for PP (HR = 1.10, 95% CI: 0.84 to 1.45, p = 0.496). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs. CONCLUSIONS: Plaque progression, identified by follow-up CCTA, mediates the relationship between NAFLD and MACEs. KEY POINTS: The incidence of CCTA-identified PP was higher for participants with NAFLD than those without NAFLD (248/752 [33.0%] vs. 155/931 [16.6%], p < 0.001). Participants with NAFLD had a lower 9.7-year event-free survival rate than those without NAFLD (66.4% vs. 80.9%, log-rank p < 0.001). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs.

Challenges in treatment of a patient suffering from neuroendocrine tumor G1 of the hilar bile duct: a case report.

BACKGROUND: Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are extremely rare in the biliary tract. Currently, there are no guidelines for the diagnosis and treatment of biliary NETs. We presented a case with NETs G1 of the hilar bile duct and the challenges for her treatment. CASE PRESENTATION: A 24-year-old woman was presented to our department with painless jaundice and pruritus, and the preoperative diagnosis was Bismuth type II hilar cholangiocarcinoma. She underwent Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy. Unexpectedly, postoperative pathological and immunohistochemical examination indicated a perihilar bile duct NETs G1 with the microscopic invasion of the resected right hepatic duct. Then the patient received 3 cycles of adjuvant chemotherapy (Gemcitabine and tegafur-gimeracil-oteracil potassium capsule). At present, this patient has been following up for 24 months without recurrence or disease progression. CONCLUSION: We know little of biliary NETs because of its rarity. There are currently no guidelines for the diagnosis and treatment of biliary NETs. We reported a case of perihilar bile duct NETs G1 with R1 resection, as far as we know this is the first report. More information about biliary NETs should be registered.

Rapid analysis of components in Qizhiweitong tablets and plasma after oral administration in rats by UPLC-Q-TOF-MS/MS based on a self-developed database.

Qizhiweitong is a famous traditional Chinese prescription medicine. It has been used to treat various stomach disorders, such as functional dyspepsia, chronic gastritis and intestinal stress syndrome, for a long time and gives favorable therapeutic effects in clinical settings. However, its chemical composition and possible bioactive components are not completely known. In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) and qualitatively analyzed the chemical composition of Qizhiweitong tablet extract and the absorbed prototype constituents along with corresponding metabolites in rat plasma following oral administration of Qizhiweitong tablet on the basis of our self-developed component database that was established accurately and rapidly. We detected a total of 119 compounds and 61 xenobiotics in the Qizhiweitong tablet, which included 32 prototypes and 28 metabolites. The results of the present study laid a solid foundation for quality marker screening and an integrative pharmacology-based study on the Qizhiweitong tablet.

Coronary CT Angiography in Asymptomatic Adults with Hepatic Steatosis.

Background The long-term prognostic value of coronary CT angiography (CCTA) in asymptomatic adults with hepatic steatosis (HS) remains unknown. Purpose To evaluate the long-term prognostic value of CCTA in asymptomatic adults with HS. Materials and Methods Between January 2009 and December 2013, consecutive asymptomatic adults who underwent CCTA evaluation and unenhanced abdominal CT were prospectively enrolled. All participants were divided into two groups-with HS and without HS according to abdominal CT results. The primary end point was major adverse cardiovascular events (MACEs), defined as cardiac death, stroke, myocardial infarction, and angina requiring hospitalization. Multivariable Cox regression analysis and Kaplan-Meier analysis were used to compare survival rates. Results One thousand thirteen participants with HS and 1940 participants without HS who completed the follow-up were included (mean age, 66 years ± 10 [standard deviation] [range, 29-90 years]; 1940 men). During a median of 7.2 years of follow-up (interquartile range, 6.3-8.1), MACEs were observed in 96 of 1013 participants with HS (10%), whereas 80 of 1940 participants without HS (4%) had MACEs. In participants with a Coronary Artery Disease Reporting and Data System (CAD-RADS) category of 0, both participants with and without HS had a similar 8.8-year event-free survival rate (99.2% event-free survival rate in participants with HS vs 99.0% event-free survival rate in participants without HS, P = .77). As for participants with CAD-RADS categories 1 or 2 or 3-5, the 8.8-year event-free survival rate was lower in participants with HS than in those without HS (70.6% vs 85.2%, P < .001; 51.4% vs 71.7%, P = .03, respectively). The risk of MACEs was higher for participants with HS than for those without HS in CAD-RADS categories 1 and 2 (adjusted hazard ratio = 2.3; 95% CI: 1.4, 3.9; P < .001) and CAD-RADS categories 3-5 (adjusted HR = 2.1; 95% CI: 1.2, 3.6; P = .006) but not in the setting of CAD-RADS category 0 (adjusted HR = 5.1; 95% CI: 0.1, 398; P = .47). Conclusion Asymptomatic participants with hepatic steatosis (HS) had a worse prognosis than those without HS in the presence of coronary artery disease (CAD) at coronary CT angiography, whereas participants with HS and without CAD might have excellent clinical outcomes during a median follow-up of 7.2 years. © RSNA, 2021 Online supplemental material is available for this article.

Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice.

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.

Simulated Participants as Health Care Providers: An Innovative Approach to Interprofessional Simulation.

ABSTRACT: With the increased attention to patient safety and quality care in health care, it is imperative that prelicensure health care provider students are taught to collaborate effectively to decrease medical errors. For this project, simulated participants were utilized as health care providers for a simulation in a stand-alone nursing school without affiliation to a medical or allied health school. Both simulated participants and students reacted positively to the experience. This project demonstrated that utilizing simulated participants to portray health care providers in simulation scenarios is a feasible and well-received method of providing learning experiences that emphasize the importance of collaboration.