Optimization of nitrogen-doped sludge char preparation and mechanism study for catalytic oxidation of NO at room temperature.

Catalytic oxidation of NO at room temperature was carried out over nitrogen (N)-doped sludge char (SC) prepared from pyrolysis of municipal sewage sludge, and urea was adopted as nitrogen source. The effects of different N-doping methods (one-step and two-step method), dried sludge (DS)/urea mass ratios (5:1, 4:1, 3:1, 2:1, and 1:1), SC preparation procedures (pyrolysis only, pyrolysis with acid washing, and pyrolysis with KOH activation and acid washing), and different pyrolysis temperatures (500, 600, 700, and 800°C) on the catalytic oxidation of NO were compared to optimize the procedure for SC preparation. The results indicated that N-doping could obviously promote the catalytic performance of SC. The one-step method with simultaneous sludge pyrolysis (at 700°C), KOH activation, and N-doping (DS/urea of 3:1) was the optimal procedure for preparing the N-doped SC with the NO conversion rate of 54.7%, whereas the optimal NO conversion rate of SC without N-doping was only 47.3%. Urea worked both as carbon and nitrogen source, which could increase about 2.9%-16.5% of carbon and 24.8%-42.7% of nitrogen content in SC pyrolyzed at 700°C. N-doping significantly promoted microporosity of SC. The optimal N-doped SC showed specific surface areas of 571.38 m2/g, much higher than 374.34 m2/g of the optimal SC without N-doping. In addition, N-doping also increased amorphousness and surface basicity of SC through the formation of N-containing groups. Finally, three reaction paths, i.e. microporous reactor, active sites, and basic site control path, were proposed to explain the mechanism of N-doping on promoting the catalytic performance of NO.

Electro-dewatering performance of sewage sludge under interrupted pulsating voltage: A comparison between square shape and half-sine shape waveform.

Electro-dewatering of sewage sludge with pulsating voltage was conducted under the two different wave shapes (square wave (SQW) and half-sine wave (HSW)) to investigate the influence of wave shape and duty cycle on sludge dewatering performance. The results indicated that, under the same average voltage, the moisture content of dewatered sludge with HSW was 10.3%-35.4% lower than that with SQW, suggesting the better dewatering performance of HSW. The optimal dewatering performance was achieved at duty cycle of 80% for SQW and 60% for SHW. The chemical oxygen demand of filtrate from HSW could be 13% higher than that from SQW, indicating the higher capacity of HSW in breaking sludge cells/floc structure. The applied voltage during electrochemical treatment promoted the hydrolysis of protein in filtrate, and the main components in the electro-dewatered filtrate were fulvic acid- and humic acid-like substances. The specific energy consumption for sludge electro-dewatering were 0.015-0.269 kWh/(kg removed water), and it was almost in linear relationship with duty cycle. By overall considering the energy consumption and electro-dewatering performance, the condition of 60% duty cycle with HSW was obviously better than other conditions, which provides a meaningful guidance for future application of sludge electro-dewatering technology with pulsating voltage.

[Applications of Artificial Intelligence in Pancreatic Cystic Lesion Imaging].

As the detection rate of pancreatic cystic lesions(PCL)increases,artificial intelligence(AI)has made breakthroughs in the imaging workflow of PCL,including image post-processing,lesion detection,segmentation,diagnosis and differential diagnosis.AI-based image post-processing can optimize the quality of medical images and AI-assisted models for lesion detection,segmentation,diagnosis and differential diagnosis significantly enhance the work efficiency of radiologists.This article reviews the application progress of AI in PCL imaging and provides prospects for future research directions.

Should All Pancreatic Cystic Lesions with Worrisome or High-Risk Features Be Resected? A Clinical and Radiological Machine Learning Model May Help to Answer.

RATIONALE AND OBJECTIVES: According to current guidelines, pancreatic cystic lesions (PCLs) with worrisome or high-risk features may have overtreatment. The purpose of this study was to build a clinical and radiological based machine-learning (ML) model to identify malignant PCLs for surgery among preoperative PCLs with worrisome or high-risk features. MATERIALS AND METHODS: Clinical and radiological details of 317 pathologically confirmed PCLs with worrisome or high-risk features were retrospectively analyzed and applied to ML models including Support Vector Machine, Logistic Regression (LR), Decision Tree, Bernoulli NB, Gaussian NB, K Nearest Neighbors and Linear Discriminant Analysis. The diagnostic ability for malignancy of the optimal model with the highest diagnostic AUC in the cross-validation procedure was further evaluated in internal (n = 77) and external (n = 50) testing cohorts, and was compared to two published guidelines in internal mucinous cyst cohort. RESULTS: Ten clinical and radiological feature-based LR model was the optimal model with the highest AUC (0.951) in the cross-validation procedure. In the internal testing cohort, LR model reached an AUC, accuracy, sensitivity, and specificity of 0.927, 0.909, 0.914, and 0.905; in the external testing cohort, LR model reached 0.948, 0.900, 0.963, and 0.826. When compared to the European guidelines and the ACG guidelines, LR model demonstrated significantly better accuracy and specificity in identifying malignancy, while maintaining the same high sensitivity. CONCLUSION: Clinical- and radiological-based LR model can accurately identify malignant PCLs in patients with worrisome or high-risk features, possessing diagnostic performance better than the European guidelines as well as ACG guidelines.

USP51 promotes non-small cell lung carcinoma cell stemness by deubiquitinating TWIST1.

BACKGROUND: USP51 is a deubiquitinase (DUB), that is involved in diverse cellular processes. Accumulating evidence has demonstrated that USP51 contributes to cancer development. However, its impact on non-small cell lung carcinoma (NSCLC) cell malignancy is largely unknown. METHODS: In this study, we performed bioinformatics analysis on a dataset from The Cancer Genome Atlas to determine the association between USP51 and cell stemness marker expression in NSCLC patients. RT‒qPCR, Western blotting, and flow cytometry were performed to examine the effects of USP51 depletion on stemness marker expression. Colony formation and tumor sphere formation assays were used to assess the stemness of NSCLC cells. A cycloheximide chase time-course assay and a polyubiquitination assay were carried out to analyze the effects of USP51 on the TWIST1 protein level. TWIST1 was overexpressed in USP51 knockdown NSCLC cells to determine whether TWIST1 is required. The effect of USP51 on the in vivo growth of NSCLC cells was tested through subcutaneous injections in mice. RESULTS: We found that USP51 deubiquitinates TWIST1, which is significantly upregulated in the tissues of patients with NSCLC and is closely associated with poor prognosis. USP51 expression was positively correlated with the expression of stemness marker CD44, SOX2, NANOG, and OCT4 in NSCLC patients. USP51 depletion attenuated mRNA, protein, and cell surface expression of stemness markers and the stemness of NSCLC cells. Ectopic USP51 expression potentiated the stability of the TWIST1 protein by attenuating its polyubiquitination. In addition, TWIST1 re-expression in NSCLC cells reversed the inhibitory effect of USP51 knockdown on cell stemness. Furthermore, the in vivo results confirmed the suppressive effect of USP51 depletion on NSCLC cell growth. CONCLUSIONS: Our results show that USP51 maintains the stemness of NSCLC cells by deubiquitinating TWIST1. Knocking it down reduces both cell stemness and growth of NSCLC cells.

Transformer guided progressive fusion network for 3D pancreas and pancreatic mass segmentation.

Pancreatic masses are diverse in type, often making their clinical management challenging. This study aims to address the task of various types of pancreatic mass segmentation and detection while accurately segmenting the pancreas. Although convolution operation performs well at extracting local details, it experiences difficulty capturing global representations. To alleviate this limitation, we propose a transformer guided progressive fusion network (TGPFN) that utilizes the global representation captured by the transformer to supplement long-range dependencies lost by convolution operations at different resolutions. TGPFN is built on a branch-integrated network structure, where the convolutional neural network and transformer branches first perform separate feature extraction in the encoder, and then the local and global features are progressively fused in the decoder. To effectively integrate the information of the two branches, we design a transformer guidance flow to ensure feature consistency, and present a cross-network attention module to capture the channel dependencies. Extensive experiments with nnUNet (3D) show that TGPFN improves the mass segmentation (Dice: 73.93% vs. 69.40%) and detection accuracy (detection rate: 91.71% vs. 84.97%) on 416 private CTs, and also obtains performance improvements of mass segmentation (Dice: 43.86% vs. 42.07%) and detection (detection rate: 83.33% vs. 71.74%) on 419 public CTs.

A systematic review of prognosis predictive role of radiomics in pancreatic cancer: heterogeneity markers or statistical tricks?

OBJECTIVES: We aimed to systematically evaluate the prognostic prediction accuracy of radiomics features extracted from pre-treatment imaging in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Radiomics literature on overall survival (OS) prediction of PDAC were all included in this systematic review. A further meta-analysis was performed on the effect size of first-order entropy. Methodological quality and risk of bias of the included studies were assessed by the radiomics quality score (RQS) and prediction model risk of bias assessment tool (PROBAST). RESULTS: Twenty-three studies were finally identified in this review. Two (8.7%) studies compared prognosis prediction ability between radiomics model and TNM staging model by C-index, and both showed a better performance of the radiomics. Twenty-one (91.3%) studies reported significant predictive values of radiomics features. Nine (39.1%) studies were included in the meta-analysis, and it showed a significant correlation between first-order entropy and OS (HR 1.66, 95%CI 1.18-2.34). RQS assessment revealed validation was only performed in 5 (21.7%) studies on internal datasets and 2 (8.7%) studies on external datasets. PROBAST showed that 22 (95.7%) studies have a high risk of bias in participants because of the retrospective study design. CONCLUSION: First-order entropy was significantly associated with OS and might improve the accuracy of PDAC prognosis prediction. Existing studies were poorly validated, and it should be noted in future studies. Modification of PROBAST for radiomics studies is necessary since the strict requirements of prospective study design may not be applicable to the demand for a large sample size in the model construction stage. KEY POINTS: • Radiomics based on the primary lesion holds great potential for prognosis prediction. First-order entropy was significantly associated with the overall survival of PDAC and might improve the accuracy of current PDAC prognosis prediction. • We strongly recommend that at least an internal validation should be conducted in any radiomics study. Attention should be paid to the complex relationships between radiomics features. • Due to the close relationship between radiomics and big data, the strict requirement of prospective study design in PROABST may not be appropriate for radiomics studies. A balance between study types and sample sizes for radiomics studies needs to be found in the model construction stage.

Physicochemical Properties and in vitro Digestibility of Myofibrillar Proteins From the Scallop Mantle (Patinopecten yessoensis) Based on Ultrahigh Pressure Treatment.

The utilization of myofibrillar proteins (MPs) from the scallop mantle was limited due to its poor digestibility in vitro. In this study, structural properties and in vitro digestibility of MP were evaluated after modified by ultra-high pressure (UHP) at different pressures (0.1, 100, 200, 300, 400, and 500 MPa). The results showed that high pressure could significantly increase the ordered structure content like α-helix, inhibit the formation of disulfide bonds, and decrease surface hydrophobicity. Moreover, MP possessed the optimal solubility and in vitro digestibility properties at 200 MPa due to the minimum particle size and turbidity, relatively dense and uniform microstructure. The results indicated that the UHP treatment was an effective method to improve the digestibility of MP from scallop mantle and lay a theoretical basis for the functional foods development of poor digestion people and comprehensive utilization of scallop mantles.

Farnesoid X Receptor Deficiency Induces Hepatic Lipid and Glucose Metabolism Disorder via Regulation of Pyruvate Dehydrogenase Kinase 4.

Farnesoid X receptors (FXR) are bile acid receptors that play roles in lipid, glucose, and energy homeostasis. Synthetic FXR-specific agonists have been developed for treating nonalcoholic fatty liver disease (NAFLD) patients. However, the detailed mechanism remains unclear. To investigate the effects of FXR on NAFLD and the possible mechanism, FXR-null mice were fed either a normal or a high-fat diet. The FXR-null mice developed hepatomegaly, steatosis, accumulation of lipid droplets in liver cells, glucose metabolism disorder, and elevated serum lipid levels. Transcriptomic results showed increased expression of key lipid synthesis and glucose metabolism-related proteins. We focused on pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme involved in the regulation of glucose and fatty acid (FA) metabolism and homeostasis. Subsequently, we confirmed an increase in PDK4 expression in FXR knockout cells. Moreover, inhibition of PDK4 expression alleviated lipid accumulation in hepatocytes caused by FXR deficiency in vivo and in vitro. Our results identify FXR as a nuclear transcription factor that regulates glucose and lipid metabolism balance through PDK4, providing further insights into the mechanism of FXR agonists in the treatment of metabolic diseases.

Effect of ultrasonic treatment on the structure and functional properties of mantle proteins from scallops (Patinopecten yessoensis).

In this study, scallop mantle protein was treated by ultrasound at different powers, and then analyzed by ANS fluorescent probes, circular dichroism spectroscopy, endogenous fluorescence spectrum, DNTB colorimetry and in-vitro digestion model to elucidate the structure-function relationship. The results indicated that ultrasound can significantly affect the secondary structure of scallop mantle protein like enhancing hydrophobicity, lowering the particle size, increasing the relative contents of α-helix and decreasing contents of ß-pleated sheet, ß-turn and random coil, as well as altering intrinsic fluorescence intensity with blue shift of maximum fluorescence peak. But ultrasound had no effect on its primary structure. Moreover, the functions of scallop mantle protein were regulated by modifying its structures by ultrasound. Specifically, the protein had the highest performance in foaming property and in-vitro digestibility under ultrasonic power of 100 W, oil binding capacity under 100 W, water binding capacity under 300 W, solubility and emulsification capacity under 400 W, and emulsion stability under 600 W. These results prove ultrasonic treatment has the potential to effectively improve functional properties and quality of scallop mantle protein, benefiting in comprehensive utilization of scallop mantles.

Preparation of binder-less activated char briquettes from pyrolysis of sewage sludge for liquid-phase adsorption of methylene blue.

Binder-less activated char briquettes from sewage sludge were prepared and used for the liquid-phase adsorption of methylene blue. The properties of sludge char briquettes prepared under the different initial sludge moisture content, compression pressure, and heating rate were systematically investigated through the tests of thermogravimetric analysis (TGA), scanning electron microscopy (SEM), surface and mechanical properties, burn-off rates, methylene blue adsorption kinetics and isotherms. All of the prepared briquettes presented hierarchical structures and microporous/mesoporous characteristics, and the increase of initial sludge moisture content from 10 to 30 wt% resulted in a great increase of surface area (SBET), total pore volume (VT), apparent density, and a slight decrease of mechanical performance. The decrease of compression pressure markedly enhanced the equilibrium adsorption capacity (qe, exp), owing to the decreased diffusion resistance and blockage of diffusion pathways inside briquettes. In consideration of the mechanical performance and adsorption capacity, the optimum preparation condition was obtained at the initial moisture content of 30 wt%, compression pressure of 25 MPa, and heating rate of 10 °C/min, in which the axial compressive strength (ACS) and qe, exp of the prepared briquettes were as high as 22.2 ± 3.1 kg/m2 and 316.9 mg/g. The results also showed that the equilibrium adsorption data fit well into the pseudo-first order model system, and the adsorption isotherms followed the Langmuir isotherm model, suggesting that the adsorption process was attributed to physical adsorption, and was inclined to happen on the adsorption sites with the same energy level. Finally, the thermal regeneration tests demonstrated that the binder-less briquette had a good regeneration performance and was worthy of reusing for industrial applications.

CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR-424-5p/FoxO1 pathway in THP-1 macrophage-derived foam cells.

Prevention of ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux leads to lipid accumulation in macrophages and atherosclerosis development. C1q tumor necrosis factor-related protein 1 (CTRP1), a conserved paralog of adiponectin, has been shown to aggravate atherosclerosis via its proinflammatory property. However, very little is known about its effects on ABCA1 expression and macrophage lipid accumulation. In the current studies, we found that CTRP1 downregulated ABCA1 expression, inhibited cholesterol efflux to apoA-I and promoted lipid accumulation in THP-1 macrophage-derived foam cells. Forkhead box O1 (FoxO1), a transcriptional repressor of ABCA1, was identified as a direct target of miR-424-5p. Mechanistically, CTRP1 attenuated miR-424-5p levels and then augmented FoxO1 expression in the nucleus, which led to downregulation of ABCA1 expression and inhibition of cholesterol efflux. In conclusion, these findings suggest that CTRP1 restrains cholesterol efflux and facilitates macrophage lipid accumulation through the miR-424-5p/FoxO1/ABCA1 signaling pathway, thereby providing a novel mechanistical insight into its proatherosclerotic action.

Application of boundary electro-osmotic pulse to reduce sludge-to-wall adhesion.

Adhesion is one of the main features of sewage sludge. This paper aims at reducing sludge-to-wall adhesion through formation of a water layer induced by boundary electro-osmotic pulse (BEOP) which is characterized by distributing anodes and cathodes on one surface and exerting a pulsating current. The effects of the related parameters, including current intensity, exerting time, frequency, duty cycle (DTC), and the ratio of cathodic surface area to anodic surface area (C/A), on the adhesive stress of sewage sludge with different moisture content were thoroughly studied. The results indicated that, under the optimal conditions of BEOP, the adhesive stress of sludge with moisture content of 35%, 45%, 60% and 70% was reduced by 40.4%, 54.5%, 31%, and 24.4%, respectively. The migrations of water, ions and organic matters were also investigated to explore the functional mechanism of BEOP. The results showed that the water migrated from the anode side to the cathode side, whereas the organic matters migrated in the opposite direction. The increment of the sludge moisture content on the cathode surface was reduced with the increase of distance away from the anode. Based on theoretical modeling, the distributions of current density and temperature in sludge cake were obtained. The current flowed from anode to cathode and decayed quickly with the increase of the flowing distance, which well explained the moisture content distribution in sludge cake.

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway.

C1q tumor necrosis factor-related protein 12 (CTRP12), a conserved paralog of adiponectin, is closely associated with cardiovascular disease. However, little is known about its role in atherogenesis. The aim of this study was to examine the influence of CTRP12 on atherosclerosis and explore the underlying mechanisms. Our results showed that lentivirus-mediated CTRP12 overexpression inhibited lipid accumulation and inflammatory response in lipid-laden macrophages. Mechanistically, CTRP12 decreased miR-155-5p levels and then increased its target gene liver X receptor α (LXRα) expression, which increased ATP binding cassette transporter A1 (ABCA1)- and ABCG1-dependent cholesterol efflux and promoted macrophage polarization to the M2 phenotype. Injection of lentiviral vector expressing CTRP12 decreased atherosclerotic lesion area, elevated plasma high-density lipoprotein cholesterol levels, promoted reverse cholesterol transport (RCT), and alleviated inflammatory response in apolipoprotein E-deficient (apoE-/-) mice fed a Western diet. Similar to the findings of in vitro experiments, CTRP12 overexpression diminished miR-155-5p levels but increased LXRα, ABCA1, and ABCG1 expression in the aortas of apoE-/- mice. Taken together, these results suggest that CTRP12 protects against atherosclerosis by enhancing RCT efficiency and mitigating vascular inflammation via the miR-155-5p/LXRα pathway. Stimulating CTRP12 production could be a novel approach for reducing atherosclerosis.

Experimental study on single-mode microwave-induced tungsten wire discharge for NO conversion in NO/N2 atmosphere.

Single-mode microwave-induced tungsten wire discharge was conducted to investigate discharge phenomena in Ar, N2, NO, and their mixtures, as well as the effects of parameters, including diameter and number of tungsten wire, initial NO concentration, total gas flow rate, and microwave power, on NO conversion. The discharge phenomena verified that intense discharge could be observed in pure Ar or N2, but the discharge was considerably weakened in gas mixtures. The results of NO conversion showed that the increases of the tungsten wire diameter (0.1-0.12 mm), the tungsten wire number (1-3 wires), and microwave power (400-700 W), or the decreases of the total gas flow rate (2-0.5 L/min), and the initial NO concentration (800-200 ppm) could effectively lead to the increase of NO conversion. A maximum NO conversion of 91.5% can be achieved under the optimal conditions in the examined range. Besides, spectral analysis showed that W, O, and N ions were found in the discharge zone. After reactions, depositions were found on the inner surface of reaction tube, and the results of EDS (energy dispersive X-ray spectrometer) tests show that the depositions were composed of W, O, and N. Therefore, a portion of NO was inferred to be consumed by tungsten ions through the formation of tungsten oxides and tungsten nitrides.

Kidney xenotransplantation: Recent progress in preclinical research.

Kidney transplantation is the most effective treatment for end-stage renal disease, but is limited by the increasing shortage of deceased and living human donor kidneys. Xenotransplantation using pig organs provides the possibility to resolve the issue of organ supply shortage and is regarded as the next great medical revolution. In the past five years, there have been sequential advances toward the prolongation of life-supporting pig kidney xenograft survival in non-human primates, with the longest survival being 499 days. This progress is due to the growing availability of pigs with multi-layered genetic modifications to overcome the pathobiological barriers and the application of a costimulation blockade-based immunosuppressive regimen. These encouraging results bring the hope to initiate the clinical trials of pig kidney transplantation in the near future. In this review, we summarized the latest advances regarding pig kidney xenotransplantation in preclinical models to provide a basis for future investigation and potential clinical translation.

LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis.

Kcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE-/- mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE-/- mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.

The effectiveness of the combined problem-based learning (PBL) and case-based learning (CBL) teaching method in the clinical practical teaching of thyroid disease.

BACKGROUND: This study aimed to evaluate the effectiveness and efficiency of PBL-CBL combined teaching in thyroid surgery and make observations from the students' perspectives, based on their satisfaction with the learning process. METHODS: We prospectively enrolled 354 fourth-year students majoring in clinical medicine, along with 232 residents, from September 2014 to June 2019. These participants were randomly allocated into either the combined PBL-CBL teaching group or the traditional lecture-based classroom group to attend a course about thyroid nodules. Both pre- and post-class quizzes were conducted. An anonymous questionnaire was also administered to both groups to evaluate the students' perceptions and experiences. We compared the two teaching methods among all the students as well as with the fourth-year students and residents in subgroups. RESULTS: The traditional group's pre-class quiz scores were significantly higher than the PBL-CBL group's (as determined by a two-tailed t-test at a 95% confidence interval, T = 16.483, P < 0.001). After class, in the PBL-CBL group, the mean total quiz score and the basic knowledge and case analysis scores increased significantly (P < 0.001). The PBL-CBL group's performance improvement was significantly higher than the traditional group's (increasing from 52.76 to 70.51 vs. from 67.03 to 71.97). Furthermore, the scores for learning motivation, understanding, student-teacher interaction, the final examination, communication skills, clinical thinking skills, self-learning skills, teamwork skills, and knowledge absorption, as measured by the survey, were significantly higher in the PBL-CBL group than in the traditional group (P < 0.001). Meanwhile, the survey scores representing the amount of students' free time the course consumed were significantly lower in the PBL-CBL group than in the traditional group (P < 0.001). CONCLUSIONS: PBL combined with CBL may be an effective method for improving medical students' and residents' performance and enhancing their clinical skills.

Structural Insight into the Mechanism of 4-Aminoquinolines Selectivity for the alpha2A-Adrenoceptor.

BACKGROUND: α2A-adrenoceptor (AR) is a potential target for the treatment of degenerative diseases of the central nervous system, and α2A-AR agonists are effective drugs for this condition. However, the lack of high selectivity for α2A-AR subtype of traditional drugs greatly limits their clinic usage. METHODS: A series of homobivalent 4-aminoquinolines conjugated by two 4-aminoquinoline moieties via varying alkane linker length (C2-C12) were characterized for their affinities for each α2-AR subtype. Subsequently, docking, molecular dynamics and mutagenesis were applied to uncover the molecular mechanism. RESULTS: Most 4-aminoquinolines (4-aminoquinoline monomer, C2-C6, C8-C10) were selective for α2A-AR over α2B- and α2C-ARs. Besides, the affinities are of similar linker length-dependence for each α2-AR subtype. Among all the compounds tested, C10 has the highest affinity for α2A-AR (pKi=-7.45±0.62), which is 12-fold and 60-fold selective over α2B-AR and α2C-AR, respectively. Docking and molecular dynamics suggest that C10 simultaneously interacts with orthosteric and "allosteric" sites of the α2A-AR. The mutation of F205 decreases the affinity by 2-fold. The potential allosteric residues include S90, N93, E94 and W99. CONCLUSION: The specificity of C10 for the α2A-AR and the potential orthosteric and allosteric binding sites proposed in this study provide valuable guidance for the development of novel α2A-AR subtype selective compounds.

Syngas production from biomass pyrolysis in a continuous microwave assisted pyrolysis system.

In light of the knowledge gap in the scale-up of microwave-assisted pyrolysis technology, this study developed a continuous microwave-assisted pyrolysis (CMAP) system and examined its feasibility for syngas production. Wood pellets were pyrolyzed in the system under various temperatures, and the product distribution and energy efficiency were investigated. At a processing temperature of 800 °C, the CMAP system obtained a high quality producer gas (lower heating value 18.0 MJ/Nm3 and a 67 vol% syngas content) at a yield of 72.2 wt% or 0.80 Nm3/kg d.a.f. wood, outperforming several conventional pyrolysis processes probably due to two factors: 1) reactions between primary tar and biochar enhanced by microwave irradiation, and 2) the absence of carrier gas in the process. Energy efficiency of the process was also assessed. Potentially the electricity consumption could be reduced from 7.2 MJ to 3.45 MJ per kg of wood, enabling net electricity production from the process.