The Na+/Ca2+ exchanger 1 (NCX1) participates in the maintenance of neuronal Na+ and Ca2+ homeostasis, and it is highly expressed at synapse level of some brain areas involved in learning and memory processes, including the hippocampus, cortex, and amygdala. Furthermore, NCX1 increases Akt1 phosphorylation and enhances glutamate-mediated Ca2+ influx during depolarization in hippocampal and cortical neurons, two processes involved in learning and memory mechanisms. We investigated whether the modulation of NCX1 expression/activity might influence learning and memory processes. To this aim, we used a knock-in mouse overexpressing NCX1 in hippocampal, cortical, and amygdala neurons (ncx1.4over) and a newly synthesized selective NCX1 stimulating compound, named CN-PYB2. Both ncx1.4over and CN-PYB2-treated mice showed an amelioration in spatial learning performance in Barnes maze task, and in context-dependent memory consolidation after trace fear conditioning. On the other hand, these mice showed no improvement in novel object recognition task which is mainly dependent on non-spatial memory and displayed an increase in the active phosphorylated CaMKIIα levels in the hippocampus. Interestingly, both of these mice showed an increased level of context-dependent anxiety.Altogether, these results demonstrate that neuronal NCX1 participates in spatial-dependent hippocampal learning and memory processes.Mammalian mitochondria have small genomes encoding very limited numbers of proteins. Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria. Here, we report the identification of hundreds of circular RNAs (mecciRNAs) encoded by the mitochondrial genome. We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins. Known components involved in mitochondrial protein and RNA importation, such as TOM40 and PNPASE, interact with mecciRNAs and regulate protein entry. The expression of mecciRNAs is regulated, and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation. mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an attractive antimalarial target. Here, we discovered that the natural compound NP1024 is a nonpeptidic inhibitor of FP-2 with an IC50 value of 0.44 μmol L-1. The most exciting finding is that both in vitro and in vivo, NP1024 directly targets FP-2 in malaria parasite-infected erythrocytes as a natural fluorescent probe, thereby paving the way for an integration of malaria diagnosis and treatment.Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines, selectins, addressins and other adhesion molecules derived from endothelial cells (ECs), but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive. In this study, using hepatic ischemia/reperfusion injury (HIRI) as a model, we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells (LSECs) in acute inflammation. In mice with EC-specific Notch activation (NICeCA), HIRI induced exacerbated liver damage. https://www.selleckchem.com/products/Y-27632.html Consistently, endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor (TNF)-α expression in HIRI. Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin (EMCN), a negative regulator of leukocyte adhesion, was downregulated in LSECs from NICeCA mice. EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury. Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration, which was abrogated by EMCN overexpression in vitro. In mice deficient of RBPj, the integrative transcription factor of canonical Notch signaling, although overwhelming sinusoidal malformation aggravated HIRI, the expression of EMCN was upregulated; and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils. The Notch activation-exaggerated HIRI was compromised by blocking LFA-1, which mediated leukocyte adherence by associating with EMCN. Therefore, endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.

Conclusion Secondary PD after prior gastrectomy remains challenging, with higher EBL and rate of transfusion. However, when performed by experienced surgeons, the patients with or without previous gastrectomy show comparable postoperative clinical outcomes, such as similar duration of postoperative hospital stay and rate of postoperative pancreatic fistula. Copyright © 2020, the Korean Surgical Society.Purpose Intrahepatic recurrence has a significant effect on the survival of hepatocellular carcinoma (HCC) patients. https://www.selleckchem.com/products/Vorinostat-saha.html We aimed to determine if there are useful indicators in predicting the recurrence of liver cancer after a hepatic resection. Methods We retrospectively reviewed medical records of 210 HCC patients who underwent hepatectomy between January 2009 and December 2015. We examined clinic-pathological variables comparing 2 groups of HCC patients, either intrahepatic recurrence or not. Results We divided 184 patients into 2 groups; 94 patients (51.1%) with intrahepatic recurrence and 90 patients (48.9%) without intrahepatic recurrence. Multivariate analysis showed operation type, preoperative α-FP, postoperative protein induced by vitamin K absence-II (PIVKA-II) elevation, and multiple tumor number were closely associated with intrahepatic recurrence. The preoperative PIVKA-II level was not statistically significant in postoperative intrahepatic recurrence rate. The recurrence rate was 46.2% in 132 of 184 cases of α-FP 200 ng/mL was 38 of 184 cases, 21 of which recurred (55.3%). According to the multivariate analysis, OR ratio was 8.003 (95% confidence interval [CI], 1.549-41.353) in the α-FP 100-200 ng/mL group and 1.867 (95% CI, 0.784-4.444) in α-FP 200 ng/mL or higher group (P = 0.013). Three-year survival rate of intrahepatic recurrence patients was 80.7%, 3-year survival rate of no intrahepatic recurrence patients was 95.0%. Conclusion The intrahepatic recurrence rates were high in the group preop α-FP over 100 ng/mL. Close observation is needed. Prospective study for α-FP genes of HCC patients should be planned for predicting intrahepatic recurrence after hepatectomy. Copyright © 2020, the Korean Surgical Society.Purpose We investigated the expression of Nrf2 in colorectal cancer and its correlation with clinicopathological characteristics as well as mechanisms and roles of Nrf2 expression including cell signaling pathway, survival, proliferation, and migration. Methods Nrf2 expression was measured in 12 and 30 different colorectal cancer (CRC) tissues by western blot (WB) and immunohistochemistry (IHC), respectively. SW480 cells were used for cell proliferation and cell migration tests. The correlation between the expression of Nrf2 and clinicopathologic parameters were evaluated using the chi-square or Fisher exact test. Data are expressed as the mean ± standard deviation for 3 independent experiments. P less then 0.05 was considered statistically significant. Results Analysis of WB demonstrated that Nrf2 proteins were increased in CRC tissues, and decreased in normal tissues. IHC staining showed that the Nrf2 expression was elevated in CRC tissues, compared to matched normal tissues. When SW480 cells were suppressed with small interfering RNA of Nrf2, cell viability was inhibited, and cell apoptosis was increased. These results were found along with suppression of the phosphorylated form of extracellular signal-regulated kinase 1/2 and AKT. Conclusion This study suggests that overexpression of Nrf2 may be related to carcinogenesis and progression of CRC. Copyright © 2020, the Korean Surgical Society.Introduction Besides more common sites such as lung or peritoneum, hepatocellular carcinoma (HCC) can metastatize to rare sites. We report herein a new metastatic site of HCC the nail-bed. We also review other recently reported rare site HCC metastases (RSHM). Case Report A 66-year-old woman with a 12-year history of resected-stage IA HCC who later presented lung, spleen and brain metastases treated with surgery, systemic therapies (sorafenib, sunitinib, capecitabine) and radiotherapy. The patient was referred to us because of a painful and rapidly evolving mass in the nail-bed of the left thumb. Biopsy confirmed nail-bed HCC metastasis, and the finger was amputated. The patient died few weeks later. Conclusion This case was an opportunity for us to review RSHM. This type of metastasis seems to be an early event, in the context of advanced stage HCC with elevated protein induced by vitamin K absence-II (PIVKA II). The Lee nomogram is useful in detecting patients at high risk of developing RSHM. We would suggest insisting on systemic treatment in these metastatic patients although overall survival after RSHM diagnosis is poor. © 2020 Boldo et al.Introduction Meningitis is a commonly seen disease in the daily practice of emergency departments. Cerebrospinal fluid (CSF) examination including Gram stain and culture are crucial for identifying between bacterial and viral meningitis and should be completed prior to antibiotic administration. Hypoglycorrhachia is one of the certain independent predictors of bacterial meningitis. Case report A 69-year-old male having a past medical history of alcoholism and liver cirrhosis presented to the emergency department with intermittent fever and chills for one day. Sudden onset of a tonic-clonic seizure for a few minutes with agitation, and neck stiffness on physical examination were noted. Lumbar puncture was performed and xanthochromic turbid cerebrospinal fluid (CSF) was retrieved. CSF analysis showed pleocytosis with a white blood cell count of 4608/cm2; the neutrophil-to-lymphocyte ratio was 964. The CSF also showed extreme hypoglycorrhachia (4 mg/dL) and high protein levels (865 mg/dL) were noted. Bacterial me results can also lead to the successful outcome without neurologic deficits. GERMS.Introduction Prevotella bacilli are prevalent in the body as members of the normal flora and in some cases they can be involved in infections throughout the body. Prevotella bivia is a member of a nonpigment group found in the resident flora of the female genital tract and it is occasionally seen in the oral cavity. Case report We describe the very rare case of a 39-year-old woman with fulminant generalized peritonitis secondary to purulent salpingitis caused by Prevotella bivia. Discussion In most cases described in the literature, Prevotella bivia was mixed with aerobes and caused bacterial vaginosis and pelvic inflammatory disease, whereas in our case study Prevotella bivia was the only microbe that was isolated. The infection was fulminant and caused generalized peritonitis. Rapid and systemic infections typically occur in immunocompromised hosts, however our patient was in good health condition and immunocompetent. Conclusions Prevotella bivia may cause rapid and systemic infections, even in immunocompetent hosts.

Pancreatic cancer (PanCa) is a lethal disease. Conventional chemotherapies for PanCa offer severe systemic toxicities. Thus, the development of a successful nanomedicine-based therapeutic regimen with augmented therapeutic efficacy is highly sought. Naturally occurring pectin and modified pectin-based drug delivery systems exhibit remarkable self-targeting ability via galactose residues to various cancer cells. Herein, we developed and used an innovative approach of highly stable nanocomplexes based on modified pectin and tannic acid (MPT-NCs). The nanocomplex formation was enabled by strong intermolecular interactions between pectin and tannic acid under very mild conditions. These nanocomplexes were characterized by particle size and morphology (DLS, TEM, and SEM), FT-IR spectroscopy, and zeta potential measurements. Additionally, MPT-NCs were capable of encapsulating anticancer drugs (5-fluorouracil, gemcitabine, and irinotecan) through tannic acid binding. The in vitro bioactivity of these drug MPT-NCs were evaluated in pancreatic cancer adenocarcinoma (PDAC) cell lines (HPAF-II and PANC-1). A dose-dependent internalization of nanocomplexes was evident from microscopy and flow cytometry analysis. Both proliferation and colony formation assays indicated the anticancer potential of pectin drug nanocomplexes against PDAC cells compared to that of free drug treatments. Together, the pectin-based nanocomplexes could be a reliable and efficient drug delivery strategy for cancer therapy.Staphylococcus aureus is an important bacterial pathogen. This study utilized known staphylococcal epidemiology to track S. aureus between patients, surfaces, staff hands and air in a ten-bed intensive care unit (ICU). METHODS Patients, air and surfaces were screened for total colony counts and S. aureus using dipslides, settle plates and an MAS-100 slit-sampler once a month for 10 months. Data were modelled against proposed standards for air and surfaces, and ICU-acquired staphylococcal infection. Whole-cell genomic typing (WGS) demonstrated possible transmission pathways between reservoirs. RESULTS Frequently touched sites were more likely to be contaminated (>12 cfu/cm2; p = 0.08). Overall, 235 of 500 (47%) sites failed the surface standard (≤2.5 cfu/cm2); 20 of 40 (50%) passive air samples failed the "Index of Microbial Air" standard (2 cfu/9 cm plate/h), and 15/40 (37.5%) air samples failed the air standard ( less then 10 cfu/m3). Settle plate data were closer to surface counts than automated air data; the surface count most likely to reflect pass/fail rates for air was 5 cfu/cm2. Surface counts/bed were associated with staphylococcal infection rates (p = 0.012). Of 34 pairs of indistinguishable S. aureus, 20 (59%) showed autogenous transmission, with another four (12%) occurring between patients. Four (12%) pairs linked patients with hand-touch sites and six (18%) linked airborne S. aureus, staff hands and hand-touch sites. CONCLUSION Most ICU-acquired S. aureus infection is autogenous, while staff hands and air were rarely implicated in onward transmission. Settle plates could potentially be used for routine environmental screening. ICU staphylococcal infection is best served by admission screening, systematic cleaning and hand hygiene.Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 ± 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.The high density, large capacity, and long-term stability of DNA molecules make them an emerging storage medium that is especially suitable for the long-term storage of large datasets. The DNA sequences used in storage need to consider relevant constraints to avoid nonspecific hybridization reactions, such as the No-runlength constraint, GC-content, and the Hamming distance. In this work, a new nonlinear control parameter strategy and a random opposition-based learning strategy were used to improve the Harris hawks optimization algorithm (for the improved algorithm NOL-HHO) in order to prevent it from falling into local optima. Experimental testing was performed on 23 widely used benchmark functions, and the proposed algorithm was used to obtain better coding lower bounds for DNA storage. The results show that our algorithm can better maintain a smooth transition between exploration and exploitation and has stronger global exploration capabilities as compared with other algorithms. https://www.selleckchem.com/products/erastin.html At the same time, the improvement of the lower bound directly affects the storage capacity and code rate, which promotes the further development of DNA storage technology.An air-backed diaphragm is the key structure of most dynamic pressure sensors and plays a critical role in determining the sensor performance. Our previous analytical model investigated the influence of air cavity length on the sensitivity and bandwidth. The model found that as the cavity length decreases, the static sensitivity monotonically decreases, and the fundamental natural frequency shows a three-stage trend increasing in the long-cavity-length range, reaching a plateau value in the medium-cavity-length range, and decreasing in the short-cavity-length range, which cannot be captured by the widely used lumped model. In this study, we conducted the first experimental measurements to validate these findings. Pressure sensors with a circular polyimide diaphragm and a backing air cavity with an adjustable length were designed, fabricated, and characterized, from which the static sensitivities and fundamental natural frequencies were obtained as a function of the cavity length. A further parametric study was conducted by changing the in-plane tension in the diaphragm.

5% vs 6.7%, P=0.001), resulting in a 4-fold decrease in VA-related complications. In 204 consecutive patients who underwent VM-facilitated USG-VA, FV diameters significantly increased during VM in both vertical (mean [SD] 10.1[3]mm vs 14.4[3.2]mm; P less then 0.001) and horizontal axis (10.6[2.9]mm vs 14.5[3.2]mm, P less then 0.001). This led to a mean (SD) 38% increase in EAA from 0.8(0.2)cm2 at baseline to 1.1(0.2)cm2 during VM (P less then 0.001). CONCLUSIONS USG-VA for EPS and/or CA is feasible. Complication rates using USG-VA are low and benign. VM is a simple way to significantly increase EAA of femoral vein and can support USG-VA in difficult cases.BACKGROUND Circumferential pulmonary vein isolation (CPVI) may affect heart rate variability (HRV) via incidental lesion of parasympathetic ganglia. AIMS We studied the pattern of HRV parameters changes and relationship between 1-year HRV change post-CPVI and atrial fibrillation (AF) recurrence. METHODS   One hundred consecutive patients undergoing CPVI for paroxysmal AF were enrolled (mean [SD] age 56.0 [11.2] years, 61 males). HRV was measured the day before and after CPVI, and 1, 3, 6 and 12 months post-CPVI using 24-h Holter-recording. RESULTS During the 33-month median follow-up 38 patients experienced a late AF recurrence (LRAF). Compared with the pre-CPVI values, HRV was significantly attenuated at 1-day post-CPVI in all patients. However, at 3 to 6 months post-CPVI, all HRV parameters remained significantly attenuated for 12 months post-CPVI in LRAF-free patients but not in those with LRAF. On multivariate Cox-analysis, early AF recurrence within the blanking period (HR 4.87, P 25 ms versus ≤25 ms (Log-Rank p=0.004). CONCLUSIONS Sustained parasympathetic denervation during 12 months after CPVI was a marker of successful CPVI, whereas a 3-month post-CPVI SDNN reduction (ΔSDNN(post-CA[3 m])) of ≤ 25 ms predicted LRAF occurrence.BACKGROUND Telbivudine (LdT) and tenofovir (TDF) are widely used in pregnant women to prevent vertical transmission; however, limited data are available on the differences in clinical efficacy and safety between the two drugs. METHODS A total of 307 hepatitis B e antigen (HBeAg)-positive pregnant women with complete follow-up data were enrolled, the patients with alanine aminotransferase (ALT) levels 0.05). CONCLUSIONS This study revealed that the clinical efficacy in LdT- or TDF-treated HBeAg-positive Chinese pregnant women is similar, and gastrointestinal adverse effects occurred more frequently in TDF-treated patients.BACKGROUND Interactive digital technology use is integral to adolescents' lives and has been associated with both health benefits and risks. Previous studies have largely focused on measuring the quantity of technology use or understanding the use of specific platforms. To better understand adolescents' interactive digital technology use, we need new approaches that consider technology interactions and their importance. OBJECTIVE This study aimed to develop an assessment tool to evaluate adolescents' digital technology interactions and their perceived importance. METHODS We used a validated scale development approach comprising 2 initial steps to create an item pool item pool development and item pool refinement. These steps relied upon empirical literature review and an expert convening. We then evaluated the item pool using a Web-based survey. Data were collected via Qualtrics panel recruitment from a national sample of 12- to 18-year-olds. Participant data were randomly split into a development subsample fffline environment, and (3) technology for social connection. CONCLUSIONS The resulting Adolescents' Digital Technology Interactions and Importance (ADTI) scale is a promising and psychometrically validated tool for identifying the importance of distinct technology interactions. The scale is informed by relevant theory and expert input. The 3 subscales have utility for future studies to understand whether certain subscale score ranges are associated with health or well-being outcomes. ©Megan A Moreno, Kole Binger, Qianqian Zhao, Jens Eickhoff. Originally published in the Journal of Medical Internet Research (http//www.jmir.org), 12.02.2020.BACKGROUND Immigrants to Canada belonging to ethnocultural minority groups are at increased risk of developing diabetes and complications, including diabetic retinopathy, and they are also less likely to be screened and treated. Improved attendance to retinopathy screening (eye tests) has the potential to reduce permanent complications, including blindness. OBJECTIVE This study aims to identify the barriers and enablers of attending diabetic retinopathy screening among ethnocultural minority immigrants living with diabetes in Quebec and Ontario, Canada, to inform the development of a behavior change intervention to improve diabetic retinopathy screening attendance. METHODS The research question draws on the needs of patients and clinicians. Using an integrated knowledge translation approach, the research team includes clinicians, researchers, and patient partners who will contribute throughout the study to developing and reviewing materials and procedures, helping to recruit participants, and disseminating fiDecember 2017, and the research ethics board approved the conduct of the study as of January 13, 2018. Data collection then began in April 2018. https://www.selleckchem.com/products/r428.html As of August 28, 2018, we have recruited 22 participants, and analysis is ongoing, with results expected to be published in 2020. CONCLUSIONS Findings from this study will inform the codevelopment of theory-informed, culturally- and linguistically-tailored interventions to support patients in attending retinopathy screening. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/15109. ©Maman Joyce Dogba, Michael H Brent, Catherine Bach, Sarah Asad, Jeremy Grimshaw, Noah Ivers, France Légaré, Holly O Witteman, Janet Squires, Xiaoqin Wang, Olivera Sutakovic, Mary Zettl, Olivia Drescher, Zack van Allen, Nicola McCleary, Marie-Claude Tremblay, Stefanie Linklater, Justin Presseau. Originally published in JMIR Research Protocols (http//www.researchprotocols.org), 12.02.2020.

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising drug delivery carriers and hyperthermia agents for the treatment of cancer. However, to ensure their safety in vivo, SPIONs must be modified in order to prevent unwanted iron release. Thus, SPIONs were coated with silica layers of different morphologies non-porous (@SiO2), mesoporous (@mSiO2) or with a combination of non-porous and mesoporous layers (@SiO2@mSiO2) deposited via a sol-gel method. The presence of SiO2 drastically changed the surface properties of the nanoparticles. The zeta potential changed from 19.6 ± 0.8 mV for SPIONs to -26.1 ± 0.1 mV for SPION@mSiO2. The Brunauer-Emmett-Teller (BET) surface area increased from 7.54 ± 0.02 m2/g for SPIONs to 101.3 ± 2.8 m2/g for SPION@mSiO2. All types of coatings significantly decreased iron release (at least 10 fold as compared to unmodified SPIONs). SPIONs and SPION@mSiO2 were tested in vitro in contact with human lung epithelial cells (A549 and BEAS-2B). Both nanoparticle types were cytocompatible, although some delay in proliferation was observed for BEAS-2B cells as compared to A549 cells, which was correlated with increased cell velocity and nanoparticles uptake.Similarity measurement is one of the key tasks in spatial data analysis. It has a great impact on applications i.e., position prediction, mining and analysis of social behavior pattern. Existing methods mainly focus on the exact matching of polylines which result in the trajectories. However, for the applications like travel/drive behavior analysis, even for objects passing by the same route the trajectories are not the same due to the accuracy of positioning and the fact that objects may move on different lanes of the road. Further, in most cases of spatial data mining, locations and sometimes sequences of locations on trajectories are most important, while how objects move from location to location (the exact geometries of trajectories) is of less interest. For the abovementioned situations, the existing approaches cannot work anymore. In this paper, we propose a grid aware approach to convert trajectories into sequences of codes, so that shape details of trajectories are neglected while emphasizing locations where trajectories pass through. Experiments with Shanghai Float Car Data (FCD) show that the proposed method can calculate trajectories with high similarity if these pass through the same locations. In addition, the proposed methods are very efficient since the data volume is considerably reduced when trajectories are converted into grid-codes.The genus Circovirus includes several species and mostly causes asymptomatic infections. Porcine circovirus 2 (PCV-2) and, with increasing evidence, Porcine circovirus 3 (PCV-3), have been associated with different clinical conditions all over the world. In 2019, a new porcine circovirus (PCV-4) was identified from diseased animals in China. Because of the lessons learned from PCV-2 and PCV-3, it appears mandatory to investigate the actual distribution of this new virus and its potential association with clinical outcomes. https://www.selleckchem.com/products/mk-8719.html To this purpose, an exploratory study to detect PCV-4 by molecular methods was performed in Italy and Spain by testing more than 300 samples of different types (serum and tissues), collected from both healthy and diseased pigs and wild boar as well. All samples, independently from the country, type, health status and host, tested PCV-4 negative. Therefore, no evidence of PCV-4 presence was found in Italy and Spain through this exploratory study. Considering the dense pig trade among European countries, its presence in the continent can similarly be considered unlikely. The reasons behind the restricted PCV-4 distribution compared to other porcine circoviruses will require further investigations. Careful surveillance might nevertheless be important since prompt recognition of PCV-4 would allow the implementation of effective countermeasures to prevent its spreading and potential economic losses.In this, work, metal inserts were joined with polyamide 6 by using the injection-molding technique. The metal parts, made of steel grade DC 04, were mechanically interlocked with polyamide 6 (PA6) by rivets as a mechanical connection between both components in the form of s polymer filling the holes in the metallic parts. The mechanical-interlocking joints made of steel/PA6 were mechanically tested in a tensile-lap-shear test. The damage behavior of the joined materials in relation to rivet number and position on the metal plate was studied. The observation of rivet deformation was also conducted by infrared IR thermography. The study showed that, for polymer-metal joined samples with fewer than three rivets, the destruction of rivets by shearing meant sample damage. On the other hand, when the polymer-metal joint was made with three or four rivets, the disruption mechanism was mostly related to the polymer part breaking. The maximal values of the joint's failure force under tensile-shear tests were achieved for samples where three rivets were used. Moreover, strong correlation was found between the surface temperature of the samples and their maximal force during the tensile-lap-shear test.Mistletoe (Viscum album) extracts have been used as alternative and complementary therapeutic preparations in multiple cancers for decades. Mistletoe lectins (ML-I, ML-II, and ML-III) are considered to be the main anticancer components of such preparations. In the present study, ML-II was transiently expressed in Nicotiana benthamiana using the pEAQ-HT expression system. Expression levels of up to 60 mg/kg of the infiltrated plant tissue were obtained, and a three-fold increase was achieved by adding the endoplasmic reticulum (ER) retention signal KDEL to the native ML-II sequence. The native protein containing His-tag and KDEL was purified by immobilized metal affinity chromatography (IMAC) and gel filtration. We found that the recombinant ML-II lectin was glycosylated and retained its carbohydrate-binding activity. In addition, we demonstrated that plant produced ML-II displayed anticancer activity in vitro, inhibiting non-small cell lung cancer H460 and A549 cells with EC50 values of 4 and 3.5 µg/mL, respectively.

AIM To determine the effectiveness of individual-based, nurse-delivered, on-campus screening and brief intervention (SBI) for hazardous alcohol use among college students. METHODS It was a parallel-design, double-blind, randomized controlled trial. Out of 793 students screened, 130 met the selection criteria of hazardous alcohol use, defined by alcohol use disorder identification test (AUDIT) score 8-19. Participants were randomly allocated to either SBI or general advice group. Both interventions were delivered by one specially trained nurse. Outcome was assessed after 3 months. Primary outcome was the change in the mean AUDIT score and the secondary outcome was difference in the proportion of students transited from the high- to low-risk category of AUDIT. General linear model with repeated measures and logistic regression were used to determine the primary and secondary outcome, respectively. RESULTS Majority (80.7%) of the participants were men. Among all the baseline demography and clinical characteristics, only family history of alcohol use was significantly different in the groups. Intention to treat analysis showed a significant but small effect (0.16) of SBI on the mean AUDIT score. Gender did not moderate the effect. SBI was also observed to have a significant effect (adjusted odds ratio 3.7 95% CI 1.529-8.850) on shifting the students from high- to low-risk AUDIT zone. CONCLUSION SBI among college students is acceptable and has a small but significant effect on alcohol use. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html In countries like India, where despite the increasing magnitude of hazardous drinking in students no formal system exists to deal with the problem, SBI might be useful. © The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.Discovering driver pathways is an essential step to uncover the molecular mechanism underlying cancer and to explore precise treatments for cancer patients. However, due to the difficulties of mapping genes to pathways and the limited knowledge about pathway interactions, most previous work focus on identifying individual pathways. In practice, two (or even more) pathways interplay and often cooperatively trigger cancer. In this study, we proposed a new approach called CDPathway to discover cooperative driver pathways. First, CDPathway introduces a driver impact quantification function to quantify the driver weight of each gene. CDPathway assumes that genes with larger weights contribute more to the occurrence of the target disease and identifies them as candidate driver genes. Next, it constructs a heterogeneous network composed of genes, miRNAs and pathways nodes based on the known intra(inter)-relations between them and assigns the quantified driver weights to gene-pathway and gene-miRNA relational edges. n/codes.php?name=CDPathway. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.Abundant evidence points to a critical role for antibodies in protection and pathology across infectious diseases. While the antibody variable domain facilitates antibody binding and the blockade of infection, the constant domain (Fc) mediates cross-talk with the innate immune system. The biological activity of the Fc region is controlled genetically via class switch recombination, resulting in the selection of distinct antibody isotypes and subclasses. However, a second modification is made to all antibodies, via post-translational changes in antibody glycosylation. Studies from autoimmunity and oncology have established the role of IgG Fc glycosylation as a key regulator of humoral immune activity. However, a growing body of literature, exploring IgG Fc glycosylation through the lens of infectious diseases, points to the role of inflammation in shaping Fc glycan profiles, the remarkable immune plasticity in antibody glycosylation across pathogen exposed populations, canonical and non-canonical functions of glycans, and the existence of antigen-specific control over antibody Fc glycosylation. Ultimately, this work provides critical new insights into the functional roles for antibody glycosylation, as well as lays the foundation for leveraging antibody glycosylation to drive prevention or control across diseases. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.To act on tissues, circulating insulin must perfuse the relevant organ and then leave the bloodstream by crossing the endothelium-a process known as insulin delivery. It has been postulated that the continuous endothelium is a rate-limiting barrier to insulin delivery but existing data are contradictory. This conflict is in part due to the limitations of current models, including the inability to maintain a constant blood pressure in animals and the absence of shear stress in cultured cells. We developed a murine cardiac ex vivo perfusion model that delivers insulin to the heart in situ at a constant flow. We hypothesized that if the endothelial barrier were rate-limiting to insulin delivery, increasing endothelial permeability would accelerate insulin action. The kinetics of myocardial insulin action were determined in the presence or absence of agents that increased endothelial permeability. Permeability was measured using Evans Blue, which binds with high affinity to albumin. During our experiments, the myocardium remained sensitive to insulin and the vasculature retained barrier integrity. Perfusion with insulin induced Akt phosphorylation in myocytes but not in the endothelium. Infusion of platelet-activating factor or vascular endothelial growth factor significantly increased permeability to albumin without altering insulin action. Amiloride, an inhibitor of fluid-phase uptake, also did not alter insulin action. These data suggest that the endothelial barrier is not rate limiting to insulin's action in the heart; its passage out of the coronary circulation is consistent with diffusion or convection. Modulation of transendothelial transport to overcome insulin resistance is unlikely to be a viable therapeutic strategy. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Our work strongly supports that spatial and temporal regulation of ERK activity is integrated to control signaling specificity from a single extracellular signal to multiple cellular processes.The lateral septum (LS), which is innervated by the hippocampus, is known to represent spatial information. However, the details of place representation in the LS, and whether this place information is combined with reward signaling, remains unknown. We simultaneously recorded from rat CA1 and caudodorsal lateral septum in rat during a rewarded navigation task and compared spatial firing in the two areas. While LS place cells are less numerous than in hippocampus, they are similar to the hippocampus in field size and number of fields per cell, but with field shape and center distributions that are more skewed toward reward. Spike cross-correlations between the hippocampus and LS are greatest for cells that have reward-proximate place fields, suggesting a role for the LS in relaying task-relevant hippocampal spatial information to downstream areas, such as the VTA.Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 65 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. https://www.selleckchem.com/products/hexamethonium-bromide.html The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.AMPARs control fast synaptic communication between neurons and their function relies on auxiliary subunits, which importantly modulate channel properties. Although it has been suggested that AMPARs can bind to TARPs with variable stoichiometry, little is known about the effect that this stoichiometry exerts on certain AMPAR properties. Here we have found that AMPARs show a clear stoichiometry-dependent modulation by the prototypical TARP γ2 although the receptor still needs to be fully saturated with γ2 to show some typical TARP-induced characteristics (i.e. an increase in channel conductance). We also uncovered important differences in the stoichiometric modulation between calcium-permeable and calcium-impermeable AMPARs. Moreover, in heteromeric AMPARs, γ2 positioning in the complex is important to exert certain TARP-dependent features. Finally, by comparing data from recombinant receptors with endogenous AMPAR currents from mouse cerebellar granule cells, we have determined a likely presence of two γ2 molecules at somatic receptors in this cell type.Adipogenesis in adulthood replaces fat cells that turn over and can contribute to the development of obesity. However, the proliferative potential of adipocyte progenitors in vivo is unknown (Faust et al., 1976; Faust et al., 1977; Hirsch and Han, 1969; Johnson and Hirsch, 1972). We addressed this by injecting labeled wild-type embryonic stem cells into blastocysts derived from lipodystrophic A-ZIP transgenic mice, which have a genetic block in adipogenesis. In the resulting chimeric animals, wild-type ES cells are the only source of mature adipocytes. We found that when chimeric animals were fed a high-fat-diet, animals with low levels of chimerism showed a significantly lower adipose tissue mass than animals with high levels of chimerism. The difference in adipose tissue mass was attributed to variability in the amount of subcutaneous adipose tissue as the amount of visceral fat was independent of the level of chimerism. Our findings thus suggest that proliferative potential of adipocyte precursors is limited and can restrain the development of obesity.Maf (c-Maf) and Mafb transcription factors (TFs) have compensatory roles in repressing somatostatin (SST+) interneuron (IN) production in medial ganglionic eminence (MGE) secondary progenitors in mice. Maf and Mafb conditional deletion (cDKO) decreases the survival of MGE-derived cortical interneurons (CINs) and changes their physiological properties. Herein, we show that (1) Mef2c and Snap25 are positively regulated by Maf and Mafb to drive IN morphological maturation; (2) Maf and Mafb promote Mef2c expression which specifies parvalbumin (PV+) INs; (3) Elmo1, Igfbp4 and Mef2c are candidate markers of immature PV+ hippocampal INs (HIN). Furthermore, Maf/Mafb neonatal cDKOs have decreased CINs and increased HINs, that express Pnoc, an HIN specific marker. Our findings not only elucidate key gene targets of Maf and Mafb that control IN development, but also identify for the first time TFs that differentially regulate CIN vs. HIN production.

Helicobacter pylori (H. pylori) is one of the main causes of gastric gancer. TNF-related apoptosis-inducing ligand (TRAIL) is a protein able to promote apoptosis in cancer cells, however not in gastric cancer, which presents resistance to apoptosis via TRAIL. It is believed that MicroRNA-106b-5p might be involved in this resistance, although its role in Gastric Cancer is unclear. We aimed to determine the expression of microRNA-106b-5p and TRAIL in patients with gastric diseases, infected by H. pylori, and understand the relationship between these genes and their role in apoptosis and the gastric cancer pathways. H. pylori was detected by PCR, gene expression analysis was performed by real-time-qPCR, and bioinformatics analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cytoscape software. A total of 244 patients were divided into groups (Control, Gastritis, and Cancer); H. pylori was detected in 42.2% of the samples. The cancer group had a poor expression of TRAIL (p less then 0.0001) and overexpression of microRNA-106b-5p (p = 0.0005), however, our results confirmed that these genes are not directly related to each other although both are apoptosis-related regulators. Our results also indicated that H. https://www.selleckchem.com/products/CP-690550.html pylori decreases microRNA-106b-5p expression and that this is a carcinogenic bacterium responsible for gastric diseases.The chemical composition of eight (seven shoot and one inflorescence) essential oils (EOs) of Rh. tomentosum H. plants growing in Eastern Lithuania is reported. The plant material was collected during different phases of vegetation (from April to October). The oils were obtained by hydrodistillation from air-dried aerial parts (leaves and inflorescences). In total, up to 70 compounds were identified by GC-MS and GC (flame-ionization detector, FID); they comprised 91.0 ± 4.7%-96.2 ± 3.1% of the oil content. Sesquiterpene hydrocarbons (54.1 ± 1.5%-76.1 ± 4.5%) were found to be the main fraction. The major compounds were palustrol (24.6 ± 2.6%-33.5 ± 4.4%) and ledol (18.0 ± 2.9%-29.0 ± 5.0%). Ascaridol isomers (7.0 ± 2.4%-14.0 ± 2.4% in three oils), myrcene (7.2 ± 0.3% and 10.1 ± 1.3%), lepalol (3.3 ± 0.3% and 7.9 ± 3.0%), and cyclocolorenone isomers (4.1 ± 2.5%) were determined as the third main constituents. The toxic activity of marsh rosemary inflorescence and shoot oils samples was evaluated using a brine sy at yeast Saccharomyces cerevisiae-modified electrodes. The subjection of yeast cells to vapors of EO resulted in a three to four-fold increase of electrode responses due to the disruption of yeast cell membranes.BACKGROUND Dental treatments often cause pain and anxiety in patients. Virtual reality (VR) is a novel procedure that can provide distraction during dental procedures or prepare patients to receive such type of treatments. This meta-analysis is the first to gather evidence on the effectiveness of VR on the reduction of pain (P) and dental anxiety (DA) in patients undergoing dental treatment, regardless of age. METHODS MEDLINE, CENTRAL, PubMed, EMBASE, Wiley Library and Web of Science were searched for scientific articles in November 2019. The keywords used were "virtual reality", "distraction systems", "dental anxiety" and "pain". Studies where VR was used for children and adults as a measure against anxiety and pain during dental treatments were included. VR was defined as a three-dimensional environment that provides patients with a sense of immersion, transporting them to appealing and interactive settings. Anxiety and pain results were assessed during dental treatments where VR was used, and in standard care situations. RESULTS 31 studies were identified, of which 14 met the inclusion criteria. Pain levels were evaluated in four studies (n = 4), anxiety levels in three (n = 3) and anxiety and pain together in seven (n = 7). Our meta-analysis was based on ten studies (n = 10). The effect of VR was studied mainly in the pediatric population (for pain SMD = -0.82). In the adult population, only two studies (not significant) were considered. CONCLUSIONS The findings of the meta-analysis show that VR is an effective distraction method to reduce pain and anxiety in patients undergoing a variety of dental treatments; however, further research on VR as a tool to prepare patients for dental treatment is required because of the scarcity of studies in this area.Pig embryo transfer (ET) is burdened by high embryo mortality, with cytokines playing a significant role in recruitment of immune cells during embryo attachment and placentation. We hereby tested if their levels in endometrium and placenta from sows carrying hemi-allogeneic (artificially inseminated sows; C+ positive control) or allogeneic embryos (sows subjected to ET; ET) during peri-implantation (D18) or post-implantation (D24) are suitable mirrors of embryo rejection or tolerance after ET. Non-pregnant sows (C-) were used as negative controls. A set of cytokines was assayed in the tissues through multiplexed microsphere-based flow cytometry (Luminex xMAP, Millipore. USA). Fewer (58.7%. p less then 0.003) conceptuses were recovered at D24 after ET compared to C+ (80.9%); with more than 20% of the ET conceptuses being developmentally delayed. Cytokine levels shifted during implantation. Anti-inflammatory IL-10 levels were significantly (p less then 0.05) lower in ET sows compared to C+ at D24 of pregnancy. The C+ controls (carrying hemi-allogeneic embryos) consistently showed higher levels of pro-inflammatory TNF-α, IFN-γ, and IL-2 cytokines at D18 and IL-1α at D24, compared to the ET group. This clear dysregulation of pro- and anti-inflammatory cytokine levels in sows subjected to ET could be associated with an impaired maternal immune tolerance, explaining the high embryonic mortality of ET programs.Brassica rapa is an important Chinese vegetable crop that is beneficial to human health. The primary factor affecting B. rapa yield is low temperature, which promotes bolting and flowering, thereby lowering its commercial value. However, quickened bolting and flowering can be used for rapid breeding. Therefore, studying the underlying molecular mechanism of vernalization in B. rapa is crucial for solving production-related problems. Here, the transcriptome of two B. rapa accessions were comprehensively analyzed during different vernalization periods. During vernalization, a total of 974,584,022 clean reads and 291.28 Gb of clean data were obtained. Compared to the reference genome of B. rapa, 44,799 known genes and 2280 new genes were identified. A self-organizing feature map analysis of 21,035 differentially expressed genes was screened in two B. rapa accessions, 'Jin Wawa' and 'Xiao Baojian'. The analysis indicated that transcripts related to the plant hormone signal transduction, starch and sucrose metabolism, photoperiod and circadian clock, and vernalization pathways changed notably at different vernalization periods.

This review focuses on current advances in researches of gasdermin family. The distinctive expression patterns and biological roles of members in this family were discussed. Most of them exhibit pore-forming activity on cell membranes and are executors for programmed cell death with cytokines release, and play roles in cancers and inflammation-driven diseases. Therefore, they can be used as potential therapeutic targets to treat related diseases.BACKGROUND How clinical teams function varies across sites and may affect follow-up of abnormal fecal immunochemical test (FIT) results. AIMS This study aimed to identify the characteristics of clinical practices associated with higher diagnostic colonoscopy completion after an abnormal FIT result in a multi-site integrated safety-net system. METHODS We distributed survey questionnaires about tracking and follow-up of abnormal FIT results to primary care team members across 11 safety-net clinics from January 2017 to April 2017. Surveys were distributed at all-staff clinic meetings and electronic surveys sent to those not in attendance. Participants received up to three reminders to complete the survey. RESULTS Of the 501 primary care team members identified, 343 (68.5%) completed the survey. In the four highest-performing clinics, nurse managers identified at least two team members who were responsible for communicating abnormal FIT results to patients. Additionally, team members used a clinic-based registry to track patients with abnormal FIT results until colonoscopy completion. Compared to higher-performing clinics, lower-performing clinics more frequently cited competing health issues (56% vs. 40%, p = 0.03) and lack of patient priority (59% vs. 37%, p  less then  0.01) as barriers and were also more likely to discuss abnormal results at a clinic visit (83% vs. 61%, p  less then  0.01). CONCLUSIONS Our findings suggest organized and dedicated efforts to communicate abnormal FIT results and track patients until colonoscopy completion through registries is associated with improved follow-up. Increased utilization of electronic health record platforms to coordinate communication and navigation may improve diagnostic colonoscopy rates in patients with abnormal FIT results.BACKGROUND Phospholipase C delta 1 (PLCD1) has been found to be abnormally expressed in various cancers. However, the potential roles of PLCD1 in esophageal squamous cell carcinoma (ESCC) are still unknown. METHODS Western blot and qPCR were used to explore PLCD1 expression in various ESCC cells. https://www.selleckchem.com/products/pf-06424439.html MTT, colony formation assays, wound-healing assay, and transwell cell invasion assay were used to examine the cell viability in vitro. Western blot, qPCR, and luciferase assays were used to investigate the effects of PLCD1 on Wnt/β-catenin signaling pathway. The xenograft models in nude mice were established to explore the roles of PLCD1 in vivo. RESULTS We found that the expression of PLCD1 in ESCC cells was significantly downregulated than that in normal esophageal epithelial cells. In addition, upregulation of PLCD1 decreased the capacity of TE-1 and EC18 cells in proliferation, invasion, and migration. Then, the expression of β-catenin/p-β-catenin, C-myc, cyclin D1, MMP9, and MMP7 was investigated. PLCD1 activity was found to be negatively associated with the expression of β-catenin, C-myc, cyclin D1, MMP9, and MMP7. Finally, the activity of PLCD1 in inhibiting ESCC proliferation in vivo was validated. CONCLUSION The inhibitory effects of PLCD1 on the proliferation, invasion, and migration of TE-1 and EC18 cells might be associated with inhibition of Wnt/β-catenin signaling pathway. PLCD1 played a key role in inhibiting ESCC carcinogenesis and progression in patients with ESCC.Since antiquity, Cannabis has provoked enormous intrigue for its potential medicinal properties as well as for its unique pharmacological effects. The elucidation of its major cannabinoid constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), led to the synthesis of new cannabinoids (termed synthetic cannabinoids) to understand the mechanisms underlying the pharmacology of Cannabis. These pharmacological tools were instrumental in the ultimate discovery of the endogenous cannabinoid system, which consists of CB1 and CB2 cannabinoid receptors and endogenously produced ligands (endocannabinoids), which bind and activate both cannabinoid receptors. CB1 receptors mediate the cannabimimetic effects of THC and are highly expressed on presynaptic neurons in the nervous system, where they modulate neurotransmitter release. In contrast, CB2 receptors are primarily expressed on immune cells. The endocannabinoids are tightly regulated by biosynthetic and hydrolytic enzymes. Accordingly, the endocannabinoid system plays a modulatory role in many physiological processes, thereby generating many promising therapeutic targets. An unintended consequence of this research was the emergence of synthetic cannabinoids sold for human consumption to circumvent federal laws banning Cannabis use. Here, we describe research that led to the discovery of the endogenous cannabinoid system and show how knowledge of this system benefitted as well as unintentionally harmed human health.Discussion section, 9th paragraph.Curcumin is a yellow-orange dye widely used as a spice, food coloring and food preservative. It also exhibits a broad range of therapeutic effects against different disorders such as cancer, diabetes, or neurodegenerative diseases. As a compound insoluble in water curcumin accumulates in cell membranes and due to this location it may indirectly lead to the observed effects by structurally altering the membrane environment. To exert strong structural effects on membrane curcumin needs to adopt a transbilayer orientation. However, there is no agreement in literature as to curcumin's orientation and its structural effects on membranes. Here, we investigated the effects of curcumin on lipid order, lipid phase transition, and local polarity in a model liposome membranes made of DMPC or DSPC using electron paramagnetic resonance (EPR) spin labeling technique. Curcumin affected lipid order at different depths within the membrane it slightly increased the phospholipid polar headgroup mobility as monitored by spectral parameters of T-PC, while along the acyl chain the ordering effect was observed in terms of order parameter S.