Postoperative alterations in ventriculoarterial coupling are an indicator of cardiovascular outcomes in liver transplant recipients.

BACKGROUND: Liver transplantation (LT) increases the heart and vessel workload in patients with cirrhotic cardiomyopathy. While the interaction of the left ventricle (LV) with the arterial system (ventriculoarterial coupling, VAC) is a key determinant of cardiovascular performance, little is known about changes in VAC after LT. Therefore, we evaluated the relationship between VAC after LT and cardiovascular outcomes. METHODS: 344 consecutive patients underwent echocardiographic assessments before and within 30 days after LT. Non-invasive arterial elastance (Ea), LV end-systolic elastance (Ees), and LV end-diastolic elastance (Eed) were calculated. The postoperative outcomes included the development of major adverse cardiovascular events (MACE) and the length of stay in the intensive care unit and hospital. RESULTS: A total of 240 patients were included in the analyses. After LT, Ea increased by 16% (P < 0.001), and Ees and contractility index of systolic velocity (S') increased by 18% (P < 0.001) and 7% (P < 0.001), respectively. The Eed increased by 6% (P < 0.001). The VAC remained unchanged (0.56 to 0.56, P = 0.912). Of these patients, 29 had MACE, and those with MACE had significantly higher postoperative VAC. Additionally, a higher postoperative VAC was an independent risk factor for a longer postoperative hospital stay (P = 0.038). CONCLUSIONS: These data suggest that ventriculoarterial decoupling is associated with poor postoperative outcomes after LT.

High Detectivity Near Infrared Organic Photodetectors Using an Asymmetric Non-Fullerene Acceptor for Optimal Nanomorphology and Suppressed Dark Current.

Recently, the development of non-fullerene acceptors (NFAs) for near-infrared (NIR) organic photodetectors (OPDs) has attracted great interest due to their excellent NIR light absorption properties. Herein, we developed NFAs by substituting an electron-donating moiety (branched alkoxy thiophene (BAT)) asymmetrically (YOR1) and symmetrically (YOR2) for the Y6 framework. YOR1 exhibited nanoscale phase separation in a film blended with PTB7-Th. Moreover, substituting the BAT unit effectively extended the absorption wavelengths of YOR1 over 1000 nm by efficient intramolecular charge transfer and extension of the conjugation length. Consequently, YOR1-OPD exhibited significantly reduced dark current and improved responsivity by simultaneously satisfying optimal nanomorphology and significant suppression of charge recombination, resulting in 1.98 × 1013 and 3.38 × 1012 Jones specific detectivity at 950 and 1000 nm, respectively. Moreover, we successfully demonstrated the application of YOR1-OPD in highly sensitive photoplethysmography sensors using NIR light. This study suggests a strategic approach for boosting the overall performance of NIR OPDs targeting a 1000 nm light signal using an all-in-one (optimal morphology, suppressed dark current, and extended NIR absorption wavelength) NFA.

Mass-produced gram-negative bacterial outer membrane vesicles activate cancer antigen-specific stem-like CD8+ T cells which enables an effective combination immunotherapy with anti-PD-1.

Despite the capability of extracellular vesicles (EVs) derived from Gram-negative and Gram-positive bacteria to induce potent anti-tumour responses, large-scale production of bacterial EVs remains as a hurdle for their development as novel cancer immunotherapeutic agents. Here, we developed manufacturing processes for mass production of Escherichia coli EVs, namely, outer membrane vesicles (OMVs). By combining metal precipitation and size-exclusion chromatography, we isolated 357 mg in total protein amount of E. coli OMVs, which was equivalent to 3.93 × 1015 particles (1.10 × 1010 particles/µg in total protein amounts of OMVs) from 160 L of the conditioned medium. We show that these mass-produced E. coli OMVs led to complete remission of two mouse syngeneic tumour models. Further analysis of tumour microenvironment in neoantigen-expressing tumour models revealed that E. coli OMV treatment causes increased infiltration and activation of CD8+ T cells, especially those of cancer antigen-specific CD8+ T cells with high expression of TCF-1 and PD-1. Furthermore, E. coli OMVs showed synergistic anti-tumour activity with anti-PD-1 antibody immunotherapy, inducing substantial tumour growth inhibition and infiltration of activated cancer antigen-specific stem-like CD8+ T cells into the tumour microenvironment. These data highlight the potent anti-tumour activities of mass-produced E. coli OMVs as a novel candidate for developing next-generation cancer immunotherapeutic agents.

Risk factors for severe postpartum hemorrhage requiring blood transfusion after cesarean delivery for twin pregnancy: a nationwide cohort study.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality. Twin pregnancy and cesarean delivery are well-known risk factors for PPH. However, few studies have investigated PPH risk factors in mothers who have undergone cesarean delivery for twin pregnancies. Therefore, this study investigated the risk factors associated with severe PPH after cesarean delivery for twin pregnancies. METHODS: We searched and reviewed the Korean Health Insurance Review and Assessment Service's claims data from July 2008 to June 2021 using the code corresponding to cesarean delivery for twin pregnancy. Severe PPH was defined as hemorrhage requiring red blood cell (RBC) transfusion during the peripartum period. The risk factors associated with severe PPH were identified among the procedure and diagnosis code variables and analyzed using univariate and multivariate logistic regressions. RESULTS: We analyzed 31,074 cesarean deliveries for twin pregnancies, and 4,892 patients who underwent cesarean deliveries for twin pregnancies and received RBC transfusions for severe PPH were included. According to the multivariate analysis, placental disorders (odds ratio, 4.50; 95% confidence interval, 4.09- 4.95; P < 0.001), general anesthesia (2.33, 2.18-2.49; P < 0.001), preeclampsia (2.20, 1.99-2.43; P < 0.001), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (2.12, 1.22-3.68; P = 0.008), induction failure (1.37, 1.07-1.76; P = 0.014), and hypertension (1.31, 1.18-1.44; P < 0.001) predicted severe PPH. CONCLUSIONS: Placental disorders, hypertensive disorders such as preeclampsia and HELLP syndrome, and induction failure increased the risk of severe PPH after cesarean delivery for twin pregnancy.

Osteopontin is a key regulator of vascular smooth muscle cell proliferation in the outflow vein of arteriovenous fistulas.

OBJECTIVES: Despite advances in the maintenance of arteriovenous fistulas (AVFs), the patency rates remain suboptimal. Most AVFs fail due to outflow vein stenosis; however, the underlying mechanism of AVF stenosis remains unclear. The present study aimed to identify key factors associated with AVF outflow stenosis. METHODS: We obtained gene expression profiling data for the outflow vein of AVF from three Gene Expression Omnibus database datasets (GSE39488, GSE97377, and GSE116268) and analyzed the common differentially expressed genes (DEGs). We evaluated a common DEG in an aortocaval mouse model and the stenotic outflow veins of AVFs collected from patients. Furthermore, we isolated vascular smooth muscle cells (VSMCs) from the inferior vena cava (IVC) of wild-type (WT) and osteopontin (Opn)-knockout (KO) mice and assessed the proliferation of VSMCs following stimulation with platelet-derived growth factors (PDGFs). RESULTS: OPN was the only common upregulated DEG among all datasets. OPN was expressed in the medial layer of the outflow vein of AVF in aortocaval mouse models and co-stained with the VSMC marker (α-smooth muscle actin). OPN expression was markedly increased in the VSMCs of stenotic outflow veins of AVF collected from patients undergoing hemodialysis compared to presurgical veins acquired during AVF formation surgery. PDGF-induced VSMC proliferation was significantly increased in the VSMCs isolated from the IVC of WT mice but not in those isolated from the IVC of Opn-KO mice. CONCLUSIONS: OPN may be a key gene involved in VSMC proliferation in the AVF outflow veins and a therapeutic target to improve the AVF patency rate.

Comparison of the perfusion index as an index of noxious stimulation in monitored anesthesia care of propofol/remifentanil and propofol/dexmedetomidine: a prospective, randomized, case-control, observational study.

BACKGROUND: Dexmedetomidine, one of the sedatives, has an analgesic effect. We aimed to investigate postoperative analgesia with dexmedetomidine as adjuvants for procedural sedation using perfusion index (PI). METHODS: In this prospective, randomized, case-control, observational study, 72 adult patients, 19-70 years, who were scheduled for chemoport insertion under monitored anesthesia care were performed. According to the group assignment, remifentanil or dexmedetomidine was simultaneously infused with propofol. The primary outcome was PI 30 min after admission to the post anesthesia care unit (PACU). And, pain severity using numerical rating scale (NRS) score and the relationship between NRS score and PI were investigated. RESULTS: During PACU staying, PI values were significantly different between the two groups PI values at 30 min after admission to the PACU were 1.3 (0.9-2.0) in the remifentanil group and 4.5 (2.9-6.8) in the dexmedetomidine group (median difference, 3; 95% CI, 2.1 to 4.2; P < 0.001). The NRS scores at 30 min after admission to the PACU were significantly lower in the dexmedetomidine group (P = 0.002). However, there was a weak positive correlation between NRS score and PI in the PACU (correlation coefficient, 0.188; P = 0.01). CONCLUSION: We could not find a significant correlation between PI and NRS score for postoperative pain control. Using PI as a single indicator of pain is insufficient. TRIAL REGISTRATION: Clinical Trial Registry of Korea, https://cris.nih.go.kr : KCT0003501, the date of registration: 13/02/2019.

Prospective comparative analysis of noninvasive body temperature monitoring using zero heat flux technology (SpotOn sensor) compared with esophageal temperature monitoring during pediatric surgery.

Maintaining body temperature in pediatric patients is critical, but it is often difficult to use currently accepted core temperature measurement methods. Several studies have validated the use of the SpotOn sensor for measuring core temperature in adults, but studies on pediatric patients are still lacking. The aim of this study was to investigate the accuracy of the SpotOn sensor compared with that of esophageal temperature measurement in pediatric patients intraoperatively. Children aged 1-8 years with American Society of Anesthesiology Physical Condition Classification I or II scheduled to undergo elective ear surgery for at least 30 min under general anesthesia were enrolled. Body core temperature was measured every 15 min after induction till the end of anesthesia with an esophageal probe, axillary probe, and SpotOn sensor. We included 49 patients, providing a total 466 paired measurements. Analysis of Pearson rank correlation between SpotOn and esophageal pairs showed a correlation coefficient (r) of 0.93 (95% confidence interval [CI] 0.92-0.94). Analysis of Pearson rank correlation between esophageal and axillary pairs gave a correlation coefficient (r) of 0.89 (95% CI 0.87-0.91). Between the SpotOn and esophageal groups, Bland-Altman analysis revealed a bias (SD, 95% limits of agreement) of -0.07 (0.17 [-0.41-0.28]). Between the esophageal and axillary groups, Bland-Altman analysis showed a bias (SD, 95% limits of agreement) of 0.45 (0.22 [0-0.89]). In pediatric patients during surgery, the SpotOn sensor showed high correlation and agreement with the esophageal probe, which is a representative core temperature measurement method.

Extracellular vesicles from in vivo liver tissue accelerate recovery of liver necrosis induced by carbon tetrachloride.

Extracellular vesicles (EVs) are nano-sized vesicles composed of proteolipid bilayers carrying various molecular signatures of the cells. As mediators of intercellular communications, EVs have gained great attention as new therapeutic agents in the field of nanomedicine. Therefore, many studies have explored the roles of cell-derived EVs isolated from cultured hepatocytes or stem cells as inducer of liver proliferation and regeneration under various pathological circumstances. However, study investigating the role of EVs directly isolated from liver tissue has not been performed. Herein, to understand the pathophysiological role and to investigate the therapeutic potential of in vivo liver EVs, we isolated EVs from both normal and carbon tetrachloride (CCl4)-induced damaged in vivo liver tissues. The in vivo EVs purified from liver tissues display typical features of EVs including spherical morphology, nano-size, and enrichment of tetraspanins. Interestingly, administration of both normal and damaged liver EVs significantly accelerated the recovery of liver tissue from CCl4-induced hepatic necrosis. This restorative action was through the induction of hepatocyte growth factor at the site of the injury. These results suggest that not only normal liver EVs but also damaged liver EVs play important pathophysiological roles of maintaining homeostasis after tissue damage. Our study, therefore, provides new insight into potentially developing in vivo EV-based therapeutics for preventing and treating liver diseases.

Profilin-1; a novel regulator of DNA damage response and repair machinery in keratinocytes.

Profilin-1 (PFN1) regulates actin polymerization and cytoskeletal growth. Despite the essential roles of PFN1 in cell integration, its subcellular function in keratinocyte has not been elucidated yet. Here we characterize the specific regulation of PFN1 in DNA damage response and repair machinery. PFN1 depletion accelerated DNA damage-mediated apoptosis exhibiting PTEN loss of function instigated by increased phosphorylated inactivation followed by high levels of AKT activation. PFN1 changed its predominant cytoplasmic localization to the nucleus upon DNA damage and subsequently restored the cytoplasmic compartment during the recovery time. Even though γH2AX was recruited at the sites of DNA double strand breaks in response to DNA damage, PFN1-deficient cells failed to recruit DNA repair factors, whereas control cells exhibited significant increases of these genes. Additionally, PFN1 depletion resulted in disruption of PTEN-AKT cascade upon DNA damage and CHK1-mediated cell cycle arrest was not recovered even after the recovery time exhibiting γH2AX accumulation. This might suggest PFN1 roles in regulating DNA damage response and repair machinery to protect cells from DNA damage. Future studies addressing the crosstalk and regulation of PTEN-related DNA damage sensing and repair pathway choice by PFN1 may further aid to identify new mechanistic insights for various DNA repair disorders.

Nanoparticles in 472 Human Cerebrospinal Fluid: Changes in Extracellular Vesicle Concentration and miR-21 Expression as a Biomarker for Leptomeningeal Metastasis.

Leptomeningeal metastasis (LM) has a poor prognosis and is difficult to diagnose and predict the response of treatment. In this study, we suggested that the monitoring of changes in the concentration of extracellular vesicles in cerebrospinal fluid could help diagnose or predict outcomes for LM. We measured nanoparticles in 472 human cerebrospinal fluid (CSF) from patients including LM with both Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) after two-step centrifugations. NTA revealed that the concentration of CSF nanoparticles was significantly increased in LM compared to other groups (2.80 × 108 /mL vs. 1.49 × 108 /mL, p < 0.01). Changes in NTA-measured nanoparticles concentration after intra-CSF chemotherapy were further examined in 33 non-small cell lung cancer patients with LM. Overall survival was longer for patients with increased EV than the others (442 vs. 165 days, p < 0.001). Markers of extracellular vesicles (CD9/CD63/CD81) significantly decreased in the EV-decreased group. MicroRNA-21 expression decreased in this favorable prognostic group, whereas it increased in the EV-decreased group. In conclusion, the elevated concentration of extracellular vesicles in cerebrospinal fluid in patients with LM may be a predictive marker for survival duration. Moreover, EV changes combined with microRNA-21 might be a biomarker for monitoring the efficacy of intracranial chemotherapy of LM in non-small cell lung cancer patients.

Twist2 promotes CD8+ T-cell differentiation by repressing ThPOK expression.

CD4/CD8 T-cell lineage differentiation is a key process in immune system development; however, a defined regulator(s) that converts the signal from T-cell receptor and co-receptor complexes into lineage differentiation remains unclear. Here, we show that Twist2 is a critical factor in CD4/CD8 thymocyte differentiation. Twist2 expression is differentially regulated by T-cell receptor signaling, leading to differentiation into the CD4 or CD8 lineage. Forced Twist2 expression perturbed CD4+ thymocyte differentiation while enhancing CD8+ thymocyte differentiation. Furthermore, Twist2 expression produced mature CD8+ thymocytes in B2m-/- mice, while its deficiency significantly impaired CD8+ cells in MHC class-II-/- and TCR transgenic mice, favoring CD8 T-cell differentiation. During CD8 lineage differentiation, Twist2 interacted with Runx3 to bind to the silencer region of the ThPOK locus, thereby blocking ThPOK expression. These findings indicate that Twist2 is a part of the transcription factor network controlling CD8 lineage differentiation.

Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro.

OBJECTIVE: Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from Artemisia, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung. However, the effects of eupatilin on endometrial fibrosis have not yet been investigated. In this study, we present the first report on the impact of eupatilin treatment on transforming growth factor beta (TGF-ß)-induced endometrial fibrosis. METHODS: The efficacy of eupatilin on TGF-ß-induced endometrial fibrosis was assessed by examining changes in morphology and the expression levels of fibrosis markers using immunofluorescence staining and quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: Eupatilin treatment significantly reduced the fibrotic activity of TGF-ß-induced endometrial fibrosis in Ishikawa cells, which displayed more circular shapes and formed more colonies. Additionally, the effects of eupatilin on fibrotic markers including alpha-smooth muscle actin, hypoxia-inducible factor 1 alpha, collagen type I alpha 1 chain, and matrix metalloproteinase-2, were evaluated in TGF-ß-induced endometrial fibrosis. The expression of these markers was highly upregulated by TGF-ß pretreatment and recovered to the levels of control cells in response to eupatilin treatment. CONCLUSION: Our findings suggest that suppression of TGF-ß-induced signaling by eupatilin might be an effective therapeutic strategy for the treatment of endometrial fibrosis.

Endometrial profilin 1: a key player in embryo-endometrial crosstalk.

OBJECTIVE: Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation. METHODS: Morphological alterations depending on the status of PFN1 expression were assessed in PFN1-depleted or control cells grown on Matrigel-coated cover glass. Day-5 mouse embryos were cocultured with Ishikawa cells. Comparisons of the rates of F-actin formation and embryo attachment were performed by measuring the stability of the attached embryo onto PFN1-depleted or control cells. RESULTS: Depletion of PFN1 in endometrial epithelial cells induced a significant reduction in cell-cell adhesion displaying less formation of colonies and a more circular cell shape. Mouse embryos co-cultured with PFN1-depleted cells failed to form actin cytoskeletal networks, whereas more F-actin formation in the direction of surrounding PFN1-intact endometrial epithelial cells was detected. Furthermore, significantly lower embryo attachment stability was observed in PFN1-depleted cells than in control cells. This may have been due to reduced endometrial receptivity caused by impaired actin cytoskeletal networks associated with PFN1 deficiency. CONCLUSION: These observations definitively demonstrate an important role of PFN1 in mediating cell-cell adhesion during the initial stage of embryo implantation and suggest a potential therapeutic target or novel biomarker for patients suffering from implantation failure.

Proton Conducting Perhydropolysilazane-Derived Gate Dielectric for Solution-Processed Metal Oxide-Based Thin-Film Transistors.

Perhydropolysilazane (PHPS), an inorganic polymer composed of Si-N and Si-H, has attracted much attention as a precursor for gate dielectrics of thin-film transistors (TFTs) due to its facile processing even at a relatively low temperature. However, an in-depth understanding of the tunable dielectric behavior of PHPS-derived dielectrics and their effects on TFT device performance is still lacking. In this study, the PHPS-derived dielectric films formed at different annealing temperatures have been used as the gate dielectric layer for solution-processed indium zinc oxide (IZO) TFTs. Notably, the IZO TFTs fabricated on PHPS annealed at 350 °C exhibit mobility as high as 118 cm2 V-1 s-1, which is about 50 times the IZO TFTs made on typical SiO2 dielectrics. The outstanding electrical performance is possible because of the exceptional capacitance of PHPS-derived dielectric caused by the limited hydrolysis reaction of PHPS at a low processing temperature (<400 °C). According to our analysis, the exceptional dielectric behavior is originated from the electric double layer formed by mobile of protons in the low temperature-annealed PHPS dielectrics. Furthermore, proton conduction through the PHPS dielectric occurs through a three-dimensional pathway by a hopping mechanism, which allows uniform polarization of the dielectric even at room temperature, leading to amplified performance of the IZO TFTs.

Composite Interlayer Consisting of Alcohol-Soluble Polyfluorene and Carbon Nanotubes for Efficient Polymer Solar Cells.

We report the synthesis of composite interlayers using alcohol-soluble polyfluorene (ASP)-wrapped single-walled carbon nanotubes (SWNTs) and their application as electron-transport layers for efficient organic solar cells. The ASP enables the individual dispersion of SWNTs in solution. The ASP-wrapped SWNT solutions are stable for 54 days without any aggregation or precipitation, indicating their very high dispersion stability. Using the ASP-wrapped SWNTs as a cathode interlayer on zinc oxide nanoparticles (ZnO NPs), a power conversion efficiency of 9.45% is obtained in PTB7-th:PC71BM-based organic solar cells, which is mainly attributed to the improvement in the short circuit current. Performance enhancements of 18 and 17% are achieved compared to those of pure ZnO NPs and ASP on ZnO NPs, respectively. In addition, the composite interlayer is applied to non-fullerene-based photovoltaics with PM6:Y6, resulting in a power conversion efficiency of up to 14.37%. The type of SWNT (e.g., in terms of diameter range and length) is not critical to the improvement in the charge-transport properties. A low density of SWNTs in the film (∼1 SWNTs/µm2 for ASP-wrapped SWNTs) has a significant influence on the charge transport in solar cells. The improvement in the performance of the solar cell is attributed to the increased internal quantum efficiency, balanced mobility between electrons and holes, and minimized charge recombination.

Characterization of human cardiac mesenchymal stromal cells and their extracellular vesicles comparing with human bone marrow derived mesenchymal stem cells.

Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90low, c-kitnegative, CD105positive phenotype and these cells express NANOG, SOX2, and GATA4. To identify the more effective type of EVs for angiogenesis among the different sources of ASCs, we isolated EVs which were derived from CMSCs with either normoxic or hypoxic condition and BM-MSCs. Our in vitro tube-formation results demonstrated that the angiogenic effects of EVs from hypoxia-treated CMSCs (CMSC-Hpx EVs) were greater than the well-known effects of EVs from BM-MSCs (BM-MSC EVs), and these were even comparable to human vascular endothelial growth factor (hVEGF), a potent angiogenic factor. Therefore, we present here that CD90lowc-kitnegativeCD105positive CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights on understanding myocardial repair. [BMB Reports 2020; 53(2): 118-123].

Toll-Like Receptors 2 and 4 Modulate Pulmonary Inflammation and Host Factors Mediated by Outer Membrane Vesicles Derived from Acinetobacter baumannii.

Pneumonia due to Gram-negative bacteria is associated with high mortality. Acinetobacter baumannii is a Gram-negative bacterium that is associated with hospital-acquired and ventilator-associated pneumonia. Bacteria have been described to release outer membrane vesicles (OMVs) that are capable of mediating systemic inflammation. The mechanism by which A. baumannii OMVs mediate inflammation is not fully defined. We sought to investigate the roles that Toll-like receptors (TLRs) play in A. baumannii OMV-mediated pulmonary inflammation. We isolated OMVs from A. baumannii cultures and intranasally introduced the OMVs into mice. Intranasal introduction of A. baumannii OMVs mediated pulmonary inflammation, which is associated with neutrophil recruitment and weight loss. In addition, A. baumannii OMVs increased the release of several chemokines and cytokines in the mouse lungs. The proinflammatory responses were partially inhibited in TLR2- and TLR4-deficient mice compared to those of wild-type mice. This study highlights the important roles of TLRs in A. baumannii OMV-induced pulmonary inflammation in vivo.

Outer Membrane Vesicles Derived From Escherichia coli Regulate Neutrophil Migration by Induction of Endothelial IL-8.

Outer membrane vesicles (OMVs) are spherical, proteolipid nanostructures that are constitutively released by Gram-negative bacteria including Escherichia coli. Although it has been shown that administration of E. coli OMVs stimulates a strong pulmonary inflammatory response with infiltration of neutrophils into the lungs in vivo, the mechanism of E. coli OMV-mediated neutrophil recruitment is poorly characterized. In this study, we observed significant infiltration of neutrophils into the mouse lung tissues in vivo, with increased expression of the neutrophil chemoattractant CXCL1, a murine functional homolog of human IL-8, on intraperitoneal administration of E. coli OMVs. In addition, OMVs and CD31-positive endothelial cells colocalized in the mouse lungs. Moreover, in vitro results showed that E. coli OMVs significantly increased IL-8 release from human microvascular endothelial cells and toll-like receptor (TLR)4 was found to be the main component for recognizing E. coli OMVs among human endothelial cell-associated TLRs. Furthermore, the transmigration of neutrophils was suppressed in the lung tissues obtained from TLR4 knockout mice treated with E. coli OMVs. Taken together, our data demonstrated that E. coli OMVs potently recruit neutrophils into the lung via the release of IL-8/CXCL1 from endothelial cells in TLR4- and NF-κB-dependent manners.

Visible-Light-Responsive High-Detectivity Organic Photodetectors with a 1 µm Thick Active Layer.

Organic photodetectors (OPDs) are attracting attention for use in flexible and portable electronic applications such as image sensors, remote sensing, optical communications, and medical sensors because of their strong photon responsivity in thin films over a broad range of wavelengths. In particular, the efficient photon-to-current conversion of OPDs under visible light allows their use in indirect X-ray detectors using scintillators to convert X-rays to visible light. The polymer poly(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2- b:4,5- b']dithiophene- co-5-(2-hexyldecyl)-1,3-bis(6-octylthieno[3,2- b]thiophen-2-yl)-4 H-thieno[3,4- c]pyrrole-4,6(5 H)-dione) (PBDTT-8ttTPD) shows strong absorption bands in the region of 500-650 nm, as well as high hole mobility, which provides excellent photoresponsivity and photon-to-current conversion efficiency. A p-n junction photodetector was fabricated by blending PBDTT-8ttTPD and [6,6]-phenyl C71 butyric acid methyl ester (PC71BM) and varying the thickness of the active layer (260-1100 nm). The PBDTT-8ttTPD:PC71BM-based OPDs show promising photodetecting properties having a low dark current of 3.72 × 10-9 A cm-2 and high responsivity of 0.39 A W-1 because of the well-controlled morphology, high molar absorption coefficient, and excellent carrier mobility of the PBDTT-8ttTPD:PC71BM layer. Consequently, the specific detectivity of the PBDTT-8ttTPD-based OPD devices was 1.13 × 1013 Jones at -2 V on irradiation with a light-emitting diode (530 nm wavelength) with a power density of 55.6 µW cm-2.

Botulinum toxin type A enhances the inhibitory spontaneous postsynaptic currents on the substantia gelatinosa neurons of the subnucleus caudalis in immature mice.

Botulinum toxin type A (BoNT/A) has been used therapeutically for various conditions including dystonia, cerebral palsy, wrinkle, hyperhidrosis and pain control. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) receive orofacial nociceptive information from primary afferents and transmit the information to higher brain center. Although many studies have shown the analgesic effects of BoNT/A, the effects of BoNT/A at the central nervous system and the action mechanism are not well understood. Therefore, the effects of BoNT/A on the spontaneous postsynaptic currents (sPSCs) in the SG neurons were investigated. In whole cell voltage clamp mode, the frequency of sPSCs was increased in 18 (37.5%) neurons, decreased in 5 (10.4%) neurons and not affected in 25 (52.1%) of 48 neurons tested by BoNT/A (3 nM). Similar proportions of frequency variation of sPSCs were observed in 1 and 10 nM BoNT/A and no significant differences were observed in the relative mean frequencies of sPSCs among 1-10 nM BoNT/A. BoNT/A-induced frequency increase of sPSCs was not affected by pretreated tetrodotoxin (0.5 µM). In addition, the frequency of sIPSCs in the presence of CNQX (10 µM) and AP5 (20 µM) was increased in 10 (53%) neurons, decreased in 1 (5%) neuron and not affected in 8 (42%) of 19 neurons tested by BoNT/A (3 nM). These results demonstrate that BoNT/A increases the frequency of sIPSCs on SG neurons of the Vc at least partly and can provide an evidence for rapid action of BoNT/A at the central nervous system.