Adiabatic versus non-adiabatic electron transfer at 2D electrode materials.

2D electrode materials are often deployed on conductive supports for electrochemistry and there is a great need to understand fundamental electrochemical processes in this electrode configuration. Here, an integrated experimental-theoretical approach is used to resolve the key electronic interactions in outer-sphere electron transfer (OS-ET), a cornerstone elementary electrochemical reaction, at graphene as-grown on a copper electrode. Using scanning electrochemical cell microscopy, and co-located structural microscopy, the classical hexaamineruthenium (III/II) couple shows the ET kinetics trend: monolayer > bilayer > multilayer graphene. This trend is rationalized quantitatively through the development of rate theory, using the Schmickler-Newns-Anderson model Hamiltonian for ET, with the explicit incorporation of electrostatic interactions in the double layer, and parameterized using constant potential density functional theory calculations. The ET mechanism is predominantly adiabatic; the addition of subsequent graphene layers increases the contact potential, producing an increase in the effective barrier to ET at the electrode/electrolyte interface.

The bridge stenting-based internal drainage in pancreatic trauma patients with main pancreatic duct injury.

Pancreatic trauma is associated with high mortality and morbidity, especially in main pancreatic duct (MPD) injuries. Here, we introduce a novel technique via the placement of bridge stenting-based internal drainage (BSID) along the injured MPD to restore pancreatic tissue integrity. Twelve patients with MPD injury underwent unobstructed BSID as physical support for healing. Six patients with peripheral organ injuries underwent operative end-to-end anastomosis of the MPD by using a polyurethane central venous catheter for the BSID, and the other six patients with isolated proximal MPD rupture received BSID via endoscopic pancreatic stent placement. The BSID technique was successfully performed in all pancreatic trauma patients without the need for a second open surgery. With this simplified BSID-based operation, a short procedure duration (242.7 ± 38.71 min in the surgical group and 100.2 ± 16.24 min in the endoscopic group) and a short hospital stay (13.0 ± 7.05 days) were achieved. However, a few complications (41.67%) still occurred, including pancreatitis, fistula, abscess, pseudocyst, cholangitis, and haemorrhage. Except for the deceased case, all postoperative courses were marked by decreases in the peripancreatic fluid collection, blood amylase recovery, and normal endocrine function. The BSID approach is a feasible surgical approach for the treatment of MPD injury and can be used endoscopically in isolated MPD injuries for its safety and convenience.

Endoscopic dissection of refractory pancreatic duct stricture via accessory pancreatic duct approach for concurrent treatment of anomalous pancreaticobiliary junction in aging patients.

BACKGROUND: Although endoscopic management of pancreatic strictures by dilation and stenting is well established, some high-grade strictures are refractory to conventional methods. Here, we report a novel technique via accessory pancreatic duct (APD) approach to simultaneously release chronic pancreatitis-associated pancreatic stricture and correct anomalous pancreaticobiliary junction (APBJ). Due to APBJ and stricture of proximal main pancreatic duct, the APD turned out to be compensatory expansion. The stiff stenosis was dissected along the axial of APD using needle-knife electrocautery or holmium laser ablation, and then the supporting stent was placed into the pancreatic body duct. By doing so, the outflow channels of pancreatic and biliary ducts were exquisitely separated. PATIENTS AND METHODS: Two patients aged 69 and 71 years underwent stricture dissection and stent insertion for fluent drainage of pancreatic juice. The postoperative course was marked by complete abdominal pain relief and normal blood amylase recovery. In the first patient, wire-guided needle-knife electrocautery under fluoroscopic control was applied to release refractory stricture. The second patient was treated by SpyGlass pancreatoscopy-guided holmium laser ablation to lift pancreatic stricture. RESULTS: Plastic stents in APD were removed at 3 months after surgery, and magnetic resonance imaging at 6 months showed strictly normal aspect of the pancreatic duct. CONCLUSION: Although both cases were successful without severe complications, we recommend this approach only for selected patients with short refractory pancreatic strictures due to chronic pancreatitis. In order to prevent severe complications (bleeding, perforation or pancreatitis), direct-view endoscopy-guided electrotomy needs to be developed.

Single-operator cholangioscopy for the treatment of concomitant gallbladder stones and secondary common bile duct stones.

BACKGROUND AND AIM: This study aims to assess the clinical validity and safety of single-operator cholangioscopy system (SOCS) for the treatment of concomitant gallbladder stones and secondary common bile duct (CBD) stones. METHODS: This retrospective study included 10 consecutive patients who had small-sized stones (< 1 cm) in both the gallbladder and CBD; the patients underwent SOCS treatment from June 2016 to December 2016. The clinical validity of this minimally invasive surgery was determined by the operation success rate, stone removal rate, postoperative hospital stay, hospitalization cost, and contrast images before and after the operation. The clinical safety was evaluated by perioperative complications and outcomes, gallbladder stone recurrence, and gallbladder contractility function. RESULTS: Both the technique success rate and the stone removal rate when using SOCS was 100%. There were no serious complications that occurred during the operation; three patients developed acute cholecystitis, and four patients underwent hyperamylasemia after the surgery. The average postoperative hospital stay was 5.8 ± 1.32 days, and the average hospitalization cost was 7466 ± 566.1 dollars. In the follow-up period, which ranged from 3 to 8 months, there was no stone residuals or recurrences in the gallbladder and CBD, and no patient showed a recurrence of biliary colic. In addition, the gallbladder contractility function was proven to be normal within 3 to 6 months after the operation. CONCLUSIONS: SOCS could successfully manage concomitant gallbladder stones and secondary CBD stones and precisely protect normal biliary function.

Metal support effects in electrocatalysis at hexagonal boron nitride.

A scanning electrochemical droplet cell technique has been employed to screen the intrinsic electrocatalytic hydrogen evolution reaction (HER) activity of hexagonal boron nitride (h-BN) nanosheets supported on different metal substrates (Cu and Au). Local (spatially-resolved) voltammetry and Tafel analysis reveal that electronic interaction with the underlying metal substrate plays a significant role in modulating the electrocatalytic activity of h-BN, with Au-supported h-BN exhibiting significantly enhanced HER charge-transfer kinetics (exchange current is ca. two orders of magnitude larger) compared to Cu-supported h-BN, making the former material the superior support in a catalytic sense.

Polycaprolactone nanofibres loaded with 20(S)-protopanaxadiol for in vitro and in vivo anti-tumour activity study.

In this work, 20(S)-protopanaxadiol (PPD)-loaded polycaprolactone (PCL) nanofibres were successfully fabricated by the electrospinning technique using Tween 80 as a solubilizer. Firstly, smooth and continuous nanofibres were collected using suitable solvents and appropriate spinning conditions. Secondly, nanofibre mats were characterized by scanning electron microscopy, thermogravimetric (TG) analysis, Fourier transform infrared spectroscopy and mechanical testing. Finally, nanofibrous membranes were evaluated using water contact angle, in vitro drug release, biodegradation test, in vitro and in vivo anti-tumour activity and cell apoptosis assay. Scanning electron microscopic observations indicated that the diameter of the drug-loaded nanofibres increased with the increase of drug concentration. TG analysis and mechanical test showed that nanofibres were equipped with great thermal and mechanical properties. Biodegradation test exhibited that the structure of fabricated nanofibres had a certain degree of change after 15 days. An in vitro release study showed that PPD from drug-loaded nanofibres could be released in a sustained and prolonged mode. The cytotoxic effect of drug-loaded nanofibre mats examined on human laryngeal carcinoma cells (Hep-2 cells) demonstrated that the prepared nanofibres had a remarkable anti-tumour effect. Meanwhile, the drug-loaded fibre mats showed a super anti-tumour effect in an in vivo anti-tumour study. All in all, PCL nanofibres could be a potential carrier of PPD for cancer treatment.

Enhanced photocatalytic efficiency of C3N4/BiFeO3 heterojunctions: the synergistic effects of band alignment and ferroelectricity.

As one of the most promising photocatalysts, graphitic carbon nitride (g-C3N4) shows a visible light response and great chemical stability. However, its relatively low photocatalytic efficiency is a major obstacle to actual applications. Here an effective and feasible method to dramatically increase the visible light photocatalytic efficiency by forming C3N4/BiFeO3 ferroelectric heterojunctions is reported, wherein the band alignment and piezo-/ferroelectricity have synergistic positive effects in accelerating the separation of the photogenerated carriers. At the optimum composition of 10 wt% BiFeO3, the heterojunction shows 1.4 times improved photocatalytic efficiency than that of the pure C3N4. Most importantly, mechanical pressing and electrical poling can also improve the photocatalytic efficiencies by 1.3 times and 1.8 times, respectively. The optimized photocatalytic efficiency is even comparable with that of some noble metal based compounds. These results not only prove the improved photocatalytic activity of the C3N4-ferroelectric heterojunctions, but also provide a new approach for designing high-performance photocatalysts by taking advantage of ferroelectricity.

Optimal teaching strategy in periodic impulsive knowledge dissemination system.

Accurately describing the knowledge dissemination process is significant to enhance the performance of personalized education. In this study, considering the effect of periodic teaching activities on the learning process, we propose a periodic impulsive knowledge dissemination system to regenerate the knowledge dissemination process. Meanwhile, we put forward learning effectiveness which is an outcome of a trade-off between the benefits and costs raised by knowledge dissemination as objective function. Further, we investigate the optimal teaching strategy which can maximize learning effectiveness, to obtain the optimal effect of knowledge dissemination affected by the teaching activities. We solve this dynamic optimization problem by optimal control theory and get the optimization system. At last we numerically solve this system in several practical examples to make the conclusions intuitive and specific. The optimal teaching strategy proposed in this paper can be applied widely in the optimization problem of personal education and beneficial for enhancing the effect of knowledge dissemination.

Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin.

BACKGROUND: Statin therapy has shown to deplete atherosclerotic plaque lipid content and induce plaque regression. However, how early the plaque lipid depletion can occur with low-density lipoprotein cholesterol (LDL-C) lowering in humans in vivo has not been fully described. METHODS: We enrolled 43 lipid treatment naïve subjects with asymptomatic carotid atherosclerosis and LDL-C ≥ 100 and ≤ 250 mg/dl. Rosuvastatin 5-20 mg/day was used to lower LDL-C levels to < 80 mg/dl. Lipid profile and carotid MRI scans were obtained at baseline, 3, 12, and 24 months. Carotid plaque lipid-rich necrotic core (LRNC) and plaque burden were measured and compared between baseline and during treatment. RESULTS: Among the 32 subjects who completed the study, at 3 months, an average dose of rosuvastatin of 11 mg/day lowered LDL-C levels by 47% (125.2 ± 24.4 mg/dl vs. 66.7 ± 17.3 mg/dl, p < 0.001). There were no statistically significant changes in total wall volume, percent wall volume or lumen volume. However, LRNC volume was significantly decreased by 7.9 mm3, a reduction of 7.3% (111.5 ± 104.2 mm3 vs. 103.6 ± 95.8 mm3, p = 0.044). Similarly, % LRNC was also significantly decreased from 18.9 ± 11.9% to 17.9 ± 11.5% (p = 0.02) at 3 months. Both LRNC volume and % LRNC continued to decrease moderately at 12 and 24 months, although this trend was not significant. CONCLUSIONS: Among a small number of lipid treatment naïve subjects, rosuvastatin therapy may induce a rapid and lasting decrease in carotid plaque lipid content as assessed by MRI. TRIAL REGISTRATION: ClinicalTrials.Gov numbers NCT00885872.

Uncoupling protein-2 negatively regulates polymorphonuclear leukocytes chemotaxis via modulating [Ca2+] influx.

OBJECTIVE: Previous studies demonstrated that uncoupling protein 2 (UCP2) plays a negative role in modulating leukocyte inflammatory responses. The mechanism underneath the role of UCP2 in modulating leukocyte inflammatory responses, however, is incompletely understood. Here, we investigated the effect of UCP2 in polymorphonuclear leukocyte (PMN) chemotaxis. METHODS AND RESULTS: First, we assessed PMN chemotaxis in zymosan-induced murine peritonitis and found that UCP2(-/-) mice had significantly more migrated PMN in peritoneal lavage compared to their wild-type littermates. In vitro transmigration assays using isolated PMN also showed that PMN from UCP2(-/-) mice migrated faster than those from wild-type mice in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP). Second, in supporting an inhibitory role of UCP2 in PMN transmigration, migrated PMN had a decreased UCP2 expression compared to nonmigrated PMN. In contrast, in streptozotocin-induced diabetic mice in which UCP2 expression was enhanced, PMN chemotaxis was reduced. Third, comparing to UCP2(+/+) PMN, UCP2(-/-) PMN had a stronger upregulation of fMLP-induced surface CD11b/CD18 and CD11a/CD18. Finally, UCP2(-/-) PMN showed a quicker and larger fMLP-triggered intracellular calcium mobilization compared to UCP2(+/+) PMN. CONCLUSIONS: Our study demonstrates that UCP2 serves as a brake in controlling PMN chemotaxis and that the effect of UCP2 on PMN chemotaxis may be through modulating calcium influx.

Down-regulation of platelet surface CD47 expression in Escherichia coli O157:H7 infection-induced thrombocytopenia.

BACKGROUND: Platelet depletion is a key feature of hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) infection. The mechanism underlying STEC-induced platelet depletion, however, is not completely understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated for the first time that platelet surface expression of CD47 was significantly decreased in C57BL6 mice treated with concentrated culture filtrates (CCF) from STEC O157:H7. STEC O157:H7 CCF treatment also led to a sharp drop of platelet counts. The reduction of cell surface CD47 was specific for platelets but not for neutrophil, monocytes and red blood cells. Down-regulation of platelet surface CD47 was also observed in isolated human platelets treated with O157:H7 CCF. Platelet surface CD47 reduction by O157:H7 CCF could be blocked by anti-TLR4 antibody but not anti-CD62 antibody. Down-regulation of platelet surface CD47 was positively correlated with platelet activation and phagocytosis by human monocyte-derived macrophages. Furthermore, the enhanced phagocytosis process of O157:H7 CCF-treated platelets was abolished by addition of soluble CD47 recombinants. CONCLUSIONS/SIGNIFICANCE: Our results suggest that platelet CD47 down-regulation may be a novel mechanism underneath STEC-induced platelet depletion, and that the interactions between CD47 and its receptor, signal regulatory protein alpha (SIRPalpha), play an essential role in modulating platelet homeostasis.

Role of junctional adhesion molecule-like protein in mediating monocyte transendothelial migration.

OBJECTIVE: Monocyte migration across the vascular endothelium of blood vessels is a key early event in atherosclerosis. The mechanisms underlying monocyte transendothelial migration (TEM), however, are still not completely understood. Here we studied the role of junctional adhesion molecule-like protein (JAML) in regulating monocyte TEM. METHODS AND RESULTS: Firstly, by Western blot and flow cytometry, we showed that JAML was strongly expressed in monocytes and monocyte surface expression of JAML was upregulated by monocyte chemotaxis protein-1 stimulation. Both monocyte adhesion to and migration across tumor necrosis factor-alpha (TNFalpha) preactivated human microvascular endothelial cell (HMEC-1) monolayers were dose-dependently reduced by anti-JAML antiserum or soluble extracellular JAML recombinant. Secondly, short-term exposure of human monocytes and THP-1 cells to advanced glycation end products increased cell surface JAML expression, which was correlated with enhanced cell adhesion and TEM. In contrast, knockdown of JAML in THP-1 monocytes decreased both adhesion and transmigration of THP-1 monocytes. Finally, direct binding assay of the soluble JAML to HMEC-1 monolayers suggested that endothelial coxsackie and adenovirus receptor (CAR) may serve as one of the ligands for JAML. CONCLUSIONS: Monocytic JAML plays a critical role in regulating monocyte TEM probably via binding to the endothelial CAR and other tight junction-associated adhesive molecules.

The heparan sulfate proteoglycan form of epithelial CD44v3 serves as a CD11b/CD18 counter-receptor during polymorphonuclear leukocyte transepithelial migration.

Leukocyte beta2-integrin CD11b/CD18 mediates the firm adhesion and subsequent transepithelial migration of polymorphonuclear leukocytes, but the identity of its counter-receptor(s) on epithelia remains elusive. Here we identified a monoclonal antibody, clone C3H7, which strongly bound to the basolateral membranes of epithelial cells and inhibited both the adhesion of epithelial cells to immobilized CD11b/CD8 and the transepithelial migration of PMNs in a physiologically relevant basolateral-to-apical direction. C3H7 antigen expression in epithelial monolayers was significantly increased by treatment with proinflammatory cytokine interferon-gamma or a combination of interferon-gamma and tumor necrosis factor-alpha. Up-regulation of C3H7 antigen was also observed in the epithelium of inflamed human colon tissues. Microsequencing and Western blotting of the purified antigen showed it to be CD44 variant 3 (CD44v3), a approximately 160-kDa membrane glycoprotein. Further studies demonstrated that this epithelial CD44v3 specifically binds to CD11b/CD18 through its heparan sulfate moieties. In summary, our study demonstrates for the first time that the heparan sulfate proteoglycan form of epithelial CD44v3 plays a critical role in facilitating PMN recruitment during inflammatory episodes via directly binding to CD11b/CD18.

Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis.

BACKGROUND: Signal regulate protein alpha (SIRPalpha) is involved in many functional aspects of monocytes. Here we investigate the role of SIRPalpha in regulating beta(2) integrin-mediated monocyte adhesion, transendothelial migration (TEM) and phagocytosis. METHODOLOGY/PRINCIPAL FINDINGS: THP-1 monocytes/macropahges treated with advanced glycation end products (AGEs) resulted in a decrease of SIRPalpha expression but an increase of beta(2) integrin cell surface expression and beta(2) integrin-mediated adhesion to tumor necrosis factor-alpha (TNFalpha)-stimulated human microvascular endothelial cell (HMEC-1) monolayers. In contrast, SIRPalpha overexpression in THP-1 cells showed a significant less monocyte chemotactic protein-1 (MCP-1)-triggered cell surface expression of beta(2) integrins, in particular CD11b/CD18. SIRPalpha overexpression reduced beta(2) integrin-mediated firm adhesion of THP-1 cells to either TNFalpha-stimulated HMEC-1 monolayers or to immobilized intercellular adhesion molecule-1 (ICAM-1). SIRPalpha overexpression also reduced MCP-1-initiated migration of THP-1 cells across TNFalpha-stimulated HMEC-1 monolayers. Furthermore, beta(2) integrin-mediated THP-1 cell spreading and actin polymerization in response to MCP-1, and phagocytosis of bacteria were both inhibited by SIRPalpha overexpression. CONCLUSIONS/SIGNIFICANCE: SIRPalpha negatively regulates beta(2) integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis, thus may serve as a critical molecule in preventing excessive activation and accumulation of monocytes in the arterial wall during early stage of atherosclerosis.

CD44v4 is a major E-selectin ligand that mediates breast cancer cell transendothelial migration.

BACKGROUND: Endothelial E-selectin has been shown to play a pivotal role in mediating cell-cell interactions between breast cancer cells and endothelial monolayers during tumor cell metastasis. However, the counterreceptor for E-selectin and its role in mediating breast cancer cell transendothelial migration remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: By assessing migration of various breast cancer cells across TNF-alpha pre-activated human umbilical vein endothelial cells (HUVECs), we found that breast cancer cells migrated across HUVEC monolayers differentially and that transmigration was E-selectin dependent. Cell surface labeling with the E-selectin extracellular domain/Fc chimera (exE-selectin/Fc) showed that the transmigration capacity of breast cancer cells was correlated to both the expression level and localization pattern of E-selectin binding protein(s) on the tumor cell surface. The exE-selectin/Fc strongly bound to metastatic MDA-MB-231, MDA-MB-435 and MDA-MB-468 cells, but not non-metastatic MCF-7 and T47D cells. Binding of exE-selectin/Fc was abolished by removal of tumor cell surface sialyl lewis x (sLe(x)) moieties. Employing an exE-selectin/Fc affinity column, we further purified the counterreceptor of E-selectin from metastatic breast cancer cells. The N-terminal protein sequence and cDNA sequence identified this E-selectin ligand as a approximately 170 kD human CD44 variant 4 (CD44v4). Purified CD44v4 showed a high affinity for E-selectin via sLe(x) moieties and, as expected, MDA-MB-231 cell adhesion to and migration across HUVEC monolayers were significantly reduced by down-regulation of tumor cell CD44v4 via CD44v4-specific siRNA. CONCLUSIONS/SIGNIFICANCE: We demonstrated, for the first time, that breast cancer cell CD44v4 is a major E-selectin ligand in facilitating tumor cell migration across endothelial monolayers. This finding offers new insights into the molecular basis of E-selectin-dependent adhesive interactions that mediate breast cancer cell transendothelial metastasis.

[Molecular typing of Neisseria meningitidis serogroup C strains with pulsed field gel electrophoresis in China].

OBJECTIVE: To study the characteristics of epidemiology and molecular typing on Neisseria meningitidis serogroup C strains associated with outbreaks of Anhui province and sporadic cases in China, using pulsed field gel electrophoresis (PFGE). METHODS: 212 Neisseria meningitidis serogroup C strains were isolated from invasive meningococcal cases, close contacts and healthy carriers, including 48 strains from Anhui province with 38 strains associated with serogroup C outbreaks. PFGE were performed by genomic DNA digestion with Nhe I restriction enzyme. The results of PFGE were analyzed by BioNumerics software (Version 4.0, Applied Maths BVBA, Belgium). RESULTS: A total number of 212 Neisseria meningitidis serogroup C isolates were typed by 43 patterns, named AH1 to AH43. In China, AH1 pattern was the major PFGE pattern with 69.3% (n = 147) of all strains, distributed in 11 provinces. Three types of PFGE patterns (AH1 to AH3) were found in 48 strains from Anhui province, in which, 93.8% (n = 45) belonged to AH1. 97.4% (n = 37) of 38 strains associated with serogroup C outbreaks in Anhui province showed AH1 pattern. A total of 53 serogroup C strains were isolated from invasive meningococcal cases with 67.9% (36/53) of AH pattern. 71.9% (87/121) of serogroup C strains isolated from contacts of invasive meningococcal cases was AH1 pattern and 63.2% (24/38) of the strains from healthy carriers showed AH1 pattern. CONCLUSION: By PFGE typing and analysis, AH1 pattern of Neisseria meningitidis serogroup C strains was proved to be the main clone which causing the outbreaks in Anhui province and might be responsible for the sporadic serogroup C meningococcal disease epidemics else where in the country.

Using a new alignment kernel function to identify secretory proteins.

As the knowledge of protein signal peptides can be used to reprogram cells in a desired way for gene therapy, signal peptides have become a crucial tool for researchers to design new drugs for targeting a particular organelle to correct a specific defect. To effectively use such a technique, however, we have to develop an automated method for fast and accurately predicting signal peptides and their cleavage sites, particularly in the post-genomic era when the number of protein sequences is being explosively increased. To realize this, the first important thing is to discriminate secretory proteins from non-secretory proteins. On the basis of the Needleman-Wunsch algorithm, we proposed a new alignment kernel function. The novel approach can be effectively used to extract the statistical properties of protein sequences for machine learning, leading to a higher prediction success rate.

Buddlin, a new compound from Buddleja asiatica.

A new compound, named buddlin (1), was isolated from the whole plant of Buddleja asiatica. Its structure was elucidated from spectral evidence.

[Application potentials of on-line near infrared spectroscopy technology in manufacturing of traditional Chinese medicine].

The characteristics of On-line Near Infrared Spectroscopy Technology are introduced and its applications in various industries, such as petro-chemical, pharmaceutical, agriculture and food are reviewed. Considering the features in TCM manufacturing, the application potentials of On-line Near Infrared Spectroscopy Technology in Manufacturing TCM are forecasted and the key problems to be solved are discussed.