DrugBank 6.0: the DrugBank Knowledgebase for 2024.

First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.

Interferon-gamma signaling drives epithelial TNF-alpha receptor-2 expression during colonic tissue repair.

Interferon-gamma (IFNγ) is traditionally recognized for its pro-inflammatory role during intestinal inflammation. Here, we demonstrate that IFNγ also functions as a pro-repair molecule by increasing TNFα receptor 2 (TNFR2 protein/TNFRSF1B gene) expression on intestinal epithelial cells (IEC) following injury in vitro and in vivo. In silico analyses identified binding sites for the IFNγ signaling transcription factor STAT1 in the promoter region of TNFRSF1B. Scratch-wounded IEC exposed to IFNγ exhibited a STAT1-dependent increase in TNFR2 expression. In situ hybridization revealed elevated Tnfrsf1b mRNA levels in biopsy-induced colonic mucosal wounds, while intraperitoneal administration of IFNγ neutralizing antibodies following mucosal injury resulted in impaired IEC Tnfrsf1b mRNA and inhibited colonic mucosal repair. These findings challenge conventional notions that "pro-inflammatory" mediators solely exacerbate damage by highlighting latent pro-repair functions. Moreover, these results emphasize the critical importance of timing and amount in the synthesis and release of IFNγ and TNFα during the inflammatory process, as they are pivotal in restoring tissue homeostasis.

Synthesis of bis(ylidene) cyclohexanones and their antifungal activity against selected plant pathogenic fungi.

Botrytis cinerea, Rhizoctonia solani and Hemileia vastatrix are three species of phytopathogenic fungi behind major crop losses worldwide. These have been selected as target models for testing the fungicide potential of a series of bis(ylidene) cyclohexanones. Although some compounds of this chemical class are known to have inhibitory activity against human pathogens, they have never been explored for the control of phytopathogens until now. In the present work, bis(ylidene) cyclohexanones were synthesized through simple, fast and low-cost base- or acid-catalyzed aldol condensation reaction and tested in vitro against B. cinerea, R. solani and H. vastatrix. bis(pyridylmethylene) cyclohexanones showed the highest activity against the target fungi. When tested at 200 nmol per mycelial plug against R. solani., these compounds completely inhibited the mycelial growth, and the most active bis(pyridylmethylene) cyclohexanone compound had an IC50 of 155.5 nmol plug-1. Additionally, bis(pyridylmethylene) cyclohexanones completely inhibited urediniospore germination of H. vastatrix, at 125 µmol L-1. The most active bis(pyridylmethylene) cyclohexanone had an IC50 value of 4.8 µmol L-1, which was estimated as approximately 2.6 times lower than that found for the copper oxychloride-based fungicide, used as control. Additionally, these substances had a low cytotoxicity against the mammalian Vero cell line. Finally, in silico calculations indicated that these compounds present physicochemical parameters regarded as suitable for agrochemicals. Bis(ylidene) cyclohexanones may constitute promising candidates for the development of novel antifungal agents for the control of relevant fungal diseases in agriculture.

Sargassum natans I Algae: An Alternative for a Greener Approach for the Synthesis of ZnO Nanostructures with Biological and Environmental Applications.

In this work, the influence of the Sargassum natans I alga extract on the morphological characteristics of synthesized ZnO nanostructures, with potential biological and environmental applications, was evaluated. For this purpose, different ZnO geometries were synthesized by the co-precipitation method, using Sargassum natans I alga extract as stabilizing agent. Four extract volumes (5, 10, 20, and 50 mL) were evaluated to obtain the different nanostructures. Moreover, a sample by chemical synthesis, without the addition of extract, was prepared. The characterization of the ZnO samples was carried out by UV-Vis spectroscopy, FT-IR spectroscopy, X-ray diffraction, and scanning electron microscopy. The results showed that the Sargassum alga extract has a fundamental role in the stabilization process of the ZnO nanoparticles. In addition, it was shown that the increase in the Sargassum alga extract leads to preferential growth and arrangement, obtaining well-defined shaped particles. ZnO nanostructures demonstrated significant anti-inflammatory response by the in vitro egg albumin protein denaturation for biological purposes. Additionally, quantitative antibacterial analysis (AA) showed that the ZnO nanostructures synthesized with 10 and 20 mL of extract demonstrated high AA against Gram (+) S. aureus and moderate AA behavior against Gram (-) P. aeruginosa, depending on the ZnO arrangement induced by the Sargassum natans I alga extract and the nanoparticles' concentration (ca. 3200 µg/mL). Additionally, ZnO samples were evaluated as photocatalytic materials through the degradation of organic dyes. Complete degradation of both methyl violet and malachite green were achieved using the ZnO sample synthesized with 50 mL of extract. In all cases, the well-defined morphology of ZnO induced by the Sargassum natans I alga extract played a key role in the combined biological/environmental performance.

Antibacterial and Anti-Inflammatory Properties of ZnO Nanoparticles Synthesized by a Green Method Using Sargassum Extracts.

The present work shows the synthesis of ZnO nanoparticles through a green method, using sargassum extracts, which provide the reducing and stabilizing compounds. The conditions of the medium in which the reaction was carried out was evaluated, that is, magnetic stirring, ultrasound assisted, and resting condition. UV-Vis, FTIR spectroscopy, and X-ray diffraction results confirmed the synthesis of ZnO with nanometric crystal size. The scanning electron microscopy analysis showed that the morphology and size of the particles depends on the synthesis condition used. It obtained particles between 20 and 200 nm in the sample without agitation, while the samples with stirring and ultrasound were 80 nm and 100 nm, respectively. ZnO nanoparticles showed antibacterial activity against Gram-positive S. aureus and Gram-negative P. aeruginosa. A quantitative analysis was performed by varying the concentration of ZnO nanoparticles. In all cases, the antibacterial activity against Gram-positives was greater than against Gram-negatives. Ultrasound-assisted ZnO nanoparticles showed the highest activity, around 99% and 80% for S. aureus and P. aeruginosa, respectively. Similar results were obtained in the study of the anti-inflammatory activity of ZnO nanoparticles; the ultrasound-assisted sample exhibited the highest percentage (93%), even above that shown by diclofenac, which was used as a reference. Therefore, the ZnO nanoparticles synthesized with sargassum extracts have properties that can be used safely and efficiently in the field of biomedicine.

Involvement of nitric oxide in the neurobiology of fear-like behavior.

Fear is an emotional reaction that arises in dangerous situations, inducing the adaptation to an existing condition. This behavior was conserved in all vertebrates throughout evolution and is observed in mammals, birds, fish, amphibians, and reptiles. The neurocircuitry of fear involves areas of the limbic system, cortical regions, midbrain, and brainstem. These areas communicate with each other so that there is an expression of fear and memory formation to deal with the same situation at another time. The effect of nitric oxide (NO) on fear modulation has been explored. NO is a gaseous compound that easily diffuses through the cell membrane and is produced through the oxidation reaction of l-Arginine to l-citrulline catalyzed by nitric oxide synthase (NOS). Activating the intracellular NO receptor (soluble guanylyl cyclase enzyme - sGC) triggers an enzymatic cascade that can culminate in plastic events in the neuron. NOS inhibitors induce anxiolytic-like responses in fear modulation, whereas NO donors promote fear- and anxiety-like behaviors. This review describes the neurobiology of fear in mammals and non-mammals, how NO is produced in the central nervous system, and how NO acts in fear-like behavior.

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[18F]F PET-CT.

BACKGROUND: Fluorine-18 sodium fluoride (Na[18F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[18F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients. METHODS AND RESULTS: Thirty-four high CV risk individuals without previous CV events were scanned with Na[18F]F PET-CT. Cardiac Na[18F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[18F]F uptake. CONCLUSIONS: In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.

Modelling the no-show of patients to exam appointments of computed tomography.

BACKGROUND: Patients' no-shows negatively impact healthcare systems, leading to resources' underutilisation, efficiency loss, and cost increase. Predicting no-shows is key to developing strategies that counteract their effects. In this paper, we propose a model to predict the no-show of ambulatory patients to exam appointments of computed tomography at the Radiology department of a large Brazilian public hospital. METHODS: We carried out a retrospective study on 8382 appointments to computed tomography (CT) exams between January and December 2017. Penalised logistic regression and multivariate logistic regression were used to model the influence of 15 candidate variables on patients' no-shows. The predictive capabilities of the models were evaluated by analysing the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC). RESULTS: The no-show rate in computerised tomography exams appointments was 6.65%. The two models performed similarly in terms of AUC. The penalised logistic regression model was selected using the parsimony criterion, with 8 of the 15 variables analysed appearing as significant. One of the variables included in the model (number of exams scheduled in the previous year) had not been previously reported in the related literature. CONCLUSIONS: Our findings may be used to guide the development of strategies to reduce the no-show of patients to exam appointments.

Assessing organophosphorus and carbamate pesticides in maize samples using MIP extraction and PSI-MS analyzes.

The indiscriminate utilization of agrochemicals causes environmental and animal life impacts. In this regard, methodologies have been developed to offer efficiency and quickness for agrochemicals detection. Due to their selectivity and molecular recognition sites, Molecular Imprinted Polymer (MIPs) have been widely employed in some areas, including biotechnology, waste analyses, foodstuff, biological fluids, and others. This work proposed developing a method to determine aminocarb, pirimicarb, dimethoate, omethoate, pyridaphenthion, and fenitrothion pesticides using molecularly imprinted polymer combined with solid-phase extraction (MIP-SPE) for clean-up and paper spray ionization mass spectrometry for their analysis. Extractions analysis for Aminocarb, Pirimicarb, and Omethoate using MIP-SPE showed better performance when compared with MIP and NIP. The R 2 values were found with R 2 > 0.98 for all pesticides, and LODs and LOQs values were 50 and 100 µg kg-1, respectively. The precision and accuracy were assessed at three concentration levels-low, medium, and high. The precision values (interday and intraday) were below 10%, and the variation of recovery was between 80 and 120% for all pesticides. Therefore, it was possible to verify the presence of two carbamates and five organophosphorus without the necessity of preconcentration samples with precision and good recovery. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05464-7.

Social Distancing, Mask Use, and Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Brazil, April-June 2020.

We assessed the associations of social distancing and mask use with symptomatic, laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in Porto Alegre, Brazil. We conducted a population-based case-control study during April-June 2020. Municipal authorities furnished case-patients, and controls were taken from representative household surveys. In adjusted logistic regression analyses of 271 case-patients and 1,396 controls, those reporting moderate to greatest adherence to social distancing had 59% (odds ratio [OR] 0.41, 95% CI 0.24-0.70) to 75% (OR 0.25, 95% CI 0.15-0.42) lower odds of infection. Lesser out-of-household exposure (vs. going out every day all day) reduced odds from 52% (OR 0.48, 95% CI 0.29-0.77) to 75% (OR 0.25, 95% CI 0.18-0.36). Mask use reduced odds of infection by 87% (OR 0.13, 95% CI 0.04-0.36). In conclusion, social distancing and mask use while outside the house provided major protection against symptomatic infection.

Daylight LED promotes photochemical ring contraction of 2-amine-4H-pyran-3-carbonitriles with consequent loss of their antifungal activity.

The initial objective of our work was to synthesize a series of 2-amino-4H-pyran-3-carbonitriles to be tested for their antifungal activities against economically relevant phytopathogenic fungi. Fourteen compounds were prepared in up to 94% yield and shown percentages of Botrytis cinerea inhibition above 70%. Despite the promising biological results, we observed that stock solutions prepared for biological tests showed color changing when kept for a few days on the laboratory bench, under room conditions, illuminated by common LED daylight tubes (4500-6000 k). This prompted us to investigate the possible photo-induced degradation of our compounds. FT-IR ATR experiments evidenced variations in the expected bands for functional of -amino-4H-pyran-3-carbonitriles stored under LED daylight. Following, HPLC-UV analysis showed reductions in the intensity of chromatographic peaks of 2-amino-4H-pyran-3-carbonitriles, and but not for solutions kept in the dark. A solution of (E)-2-amino-8-(4-nitrobenzylidene)-4-(4-nitrophenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile underwent 84.4% of conversion after 72 h of exposure to continuous LED daylight in a BOD chamber, and the reaction product was isolated in 36% yield and characterized as (E)-7-cyano-5-(4-nitrobenzylidene)-8-(4-nitrophenyl)bicyclo[4.2.0]oct-1(6)-ene-7-carboxamide (7*). Despite freshly prepared solutions of 2-amino-4H-pyran-3-carbonitriles produced antifungal activities, these solutions lost biological activity when left on the bench for a week. Besides, compound 7* formed from photo-induced degradation of 7 also showed no antifungal activity. With this, we hope to bring two contributions: (1) production of cyclobutenes through photochemical reactions of 2-amino-4H-pyran-3-carbonitriles can be carried out through exposure to simple white LED daylight; (2) biological applications of such 2-amino-4H-pyran-3-carbonitriles may be impaired by their poor photostability.

Prevalence and risk factors of chronic kidney disease in an HIV positive Mexican cohort.

BACKGROUND: HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8-16%; however, in HIV subjects, the prevalence varies between geographic regions (2-38%). The aim was to determine the prevalence of CKD and identify the associated risk factors. METHODS: A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 - Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made. RESULTS: One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4+ T cells count < 200 cells/µL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7. CONCLUSIONS: Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis. The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible.

Dynamic capacity allocation in a radiology service considering different types of patients, individual no-show probabilities, and overbooking.

BACKGROUND: We propose a mathematical model formulated as a finite-horizon Markov Decision Process (MDP) to allocate capacity in a radiology department that serves different types of patients. To the best of our knowledge, this is the first attempt at considering radiology resources with different capacities and individual no-show probabilities of ambulatory patients in an MDP model. To mitigate the negative impacts of no-show, overbooking rules are also investigated. METHODS: The model's main objective is to identify an optimal policy for allocating the available capacity such that waiting, overtime, and penalty costs are minimized. Optimization is carried out using traditional dynamic programming (DP). The model was applied to real data from a radiology department of a large Brazilian public hospital. The optimal policy is compared with five alternative policies, one of which resembles the one currently used by the department. We identify among alternative policies the one that performs closest to the optimal. RESULTS: The optimal policy presented the best performance (smallest total daily cost) in the majority of analyzed scenarios (212 out of 216). Numerical analyses allowed us to recommend the use of the optimal policy for capacity allocation with a double overbooking rule and two resources available in overtime periods. An alternative policy in which outpatients are prioritized for service (rather than inpatients) displayed results closest to the optimal policy, being also recommended due to its easy implementation. CONCLUSIONS: Based on such recommendation and observing the state of the system at any given period (representing the number of patients waiting for service), radiology department managers should be able to make a decision (i.e., define number and type of patients) that should be selected for service such that the system's cost is minimized.

The burden of low back pain in Brazil: estimates from the Global Burden of Disease 2017 Study.

BACKGROUND: The prevalence and burden of musculoskeletal (MSK) conditions are growing around the world, and low back pain (LBP) is the most significant of the five defined MSK disorders in the Global Burden of Disease (GBD) study. LBP has been the leading cause of non-fatal health loss for the last three decades. The objective of this study is to describe the current status and trends of the burden due to LBP in Brazil based on information drawn from the GBD 2017 study. METHODS: We estimated prevalence and years lived with disability (YLDs) for LBP by Brazilian federative units, sex, age group, and age-standardized between 1990 and 2017 and conducted a decomposition analysis of changes in age- and sex-specific YLD rates attributable to total population growth and population ageing for the purpose of understanding the drivers of changes in LBP YLDs rates in Brazil. Furthermore, we analyzed the changes in disability-adjusted life years (DALYs) rankings for this disease over the period. RESULTS: The results show high prevalence and burden of LBP in Brazil. LBP prevalence increased 26.83% (95% UI 23.08 to 30.41) from 1990 to 2017. This MSK condition represents the most important cause of YLDs in Brazil, where the increase in burden is mainly related to increase in population size and ageing. The LBP age-standardized YLDs rate are similar among Brazilian federative units. LBP ranks in the top three causes of DALYs in Brazil, even though it does not contribute to mortality. CONCLUSIONS: Findings from this study show LBP to be the most important cause of YLDs and the 3rd leading cause of DALYs in Brazil. The Brazilian population is ageing, and the country has been experiencing a rapid epidemiological transition, which generates an increasing number of people who need chronic care. In this scenario, more attention should be paid to the burden of non-fatal health conditions.

Aortic stiffness and central hemodynamics in treatment-naïve HIV infection: a cross-sectional study.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with a greater risk of cardiovascular disease (CVD). HIV infection causes a chronic inflammatory state and increases oxidative stress which can cause endothelial dysfunction and arterial stiffness. Aortic stiffness measured by carotid femoral-pulse wave velocity (cfPWV) and central hemodynamics are independent cardiovascular risk factors and have the prognostic ability for CVD. We assessed cfPWV and central hemodynamics in young individuals with recent HIV infection diagnosis and without antiretroviral therapy. We hypothesized that individuals living with HIV would present greater cfPWV and central hemodynamics (central systolic blood pressure and pulse pressure) compared to uninfected controls. METHODS: We recruited 51 treatment-naïve individuals living with HIV (HIV(+)) without previous CVD and 51 age- and sex-matched controls (HIV negative (-)). We evaluated traditional CVD risk factors including metabolic profile, blood pressure (BP), smoking, HIV viral load, and CD4+ T-cells count. Arterial stiffness and central hemodynamics were evaluated by cfPWV, central systolic BP, and central pulse pressure (cPP) via applanation tonometry. RESULTS: HIV(+) individuals presented a greater prevalence of smoking, reduced high-density lipoprotein cholesterol, and body mass index. 65.9% of HIV(+) individuals exhibited lymphocyte CD4+ T-cells count < 500 cells/µL. There was no difference in brachial or central BP between groups; however, HIV(+) individuals showed significantly lower cPP. We observed a greater cfPWV (mean difference = 0.5 m/s; p < 0.01) in HIV(+) compared to controls, even after adjusting for heart rate, mean arterial pressure and smoking. CONCLUSION: In the early stages of infection, non-treated HIV individuals present a greater prevalence of traditional CVD risk factors, arterial stiffness, and normal or in some cases central hemodynamics.

Cytomegalovirus and disseminated histoplasmosis-related hemophagocytic lymphohistiocytosis syndrome in an HIV-patient late presenter with IRIS: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis syndrome (HLS) is an immune-mediated life-threatening disease considered as a medical emergency, with a potentially fatal multisystem inflammatory outcome. We present a patient that developed HLS and was able to be diagnosed efficiently with the help of an academic research institute of immunology. CASE PRESENTATION: A 21 years old male Mexican with human immunodeficiency virus (HIV), late presenter; who developed cytomegalovirus (CMV) infection and a disseminated histoplasmosis-related HLS, as part of an immune reconstitution inflammatory syndrome (IRIS). The patient required a long course of corticotherapy, intravenous immunoglobulin and massive transfusions (more than 10 units in 24 h, and a total of 83 units), besides amphotericin-B and ganciclovir treatment. An academic research institute of immunology aided in the accurate diagnosis of HLS with the implementation of tests not available within the hospital, thus improving the care provided to the patient. The patient recovered, was discharged, and continue to improve. CONCLUSION: The objective of this report is to highlight the importance of having multidisciplinary support, including basic medical sciences groups providing specific tests that are sometimes very difficult to get, which provides a benefit to patients in the well-aimed diagnosis as part of applied translational medicine.

Developing a CNT-SPE Sensing Platform Based on Green Synthesized AuNPs, Using Sargassum sp.

Detection and quantification of diverse analytes such as molecules, cells receptor and even particles and nanoparticles, play an important role in biomedical research, particularly in electrochemical sensing platform technologies. In this study, gold nanoparticles (AuNPs) prepared by green synthesis from Sargassum sp. were characterized using ultraviolet-visible (UV-Vis) and Fourier transform-infrared (FT-IR) spectroscopies, X-ray diffraction (XRD), scanning electron microscopy (SEM), dynamic light scattering (DLS) and zeta potential (ζ) obtaining organic capped face-centered cubic 80-100 nm AuNPs with an excellent stability in a wide range of pH. The AuNPs were used to modify a carbon nanotubes-screen printed electrode (CNT-SPE), through the drop-casting method, to assemble a novel portable electrochemical sensing platform for glucose, using a novel combination of components, which together have not been employed. The ability to sense and measure glucose was demonstrated, and its electrochemical fundamentals was studied using cyclic voltammetry (CV). The limits of detection (LOD) and quantification (LOQ) to glucose were 50 µM and 98 µM, respectively, and these were compared to those of other sensing platforms.

New Insights in the Natural Organic Matter Fouling Mechanism of Polyamide and Nanocomposite Multiwalled Carbon Nanotubes-Polyamide Membranes.

Polyamide (PA) membranes comprise most of the reverse osmosis membranes currently used for desalination and water purification. However, their fouling mechanisms with natural organic matter (NOM) is still not completely understood. In this work, we studied three different types of PA membranes: a laboratory made PA, a commercial PA, and a multiwalled carbon nanotube (CNT-PA nanocomposite membrane during cross-flow measurements by NaCl solutions including NOM, humic acid (HA), or alginate, respectively). Molecular dynamic simulations were also used to understand the fouling process of NOM down to its molecular scale. Low molecular weight humic acid binds to the surface cavities on the PA structures that leads to irreversible adsorption induced by the high surface roughness. In addition, the larger alginate molecules show a different mechanism, due to their larger size and their ability to change shape from the globule type to the uncoiled state. Specifically, alginate molecules either bind through Ca2+ bridges or they uncoil and spread on the surface. This work shows that carbon nanotubes can help to decrease roughness and polymer mobility on the surfaces of the membranes at the molecular scale, which represents a novel method to design antifouling membranes.

Homoectoine Protects Against Colitis by Preventing a Claudin Switch in Epithelial Tight Junctions.

BACKGROUND: Inflammatory bowel diseases (IBD) are multifactorial disorders affecting millions of people worldwide with alarmingly increasing incidences every year. Dysfunction of the intestinal epithelial barrier is associated with IBD pathogenesis, and therapies include anti-inflammatory drugs that enhance intestinal barrier function. However, these drugs often have adverse side effects thus warranting the search for alternatives. Compatible solutes such as bacterial ectoines stabilize cell membranes and proteins. AIM: To unravel whether ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and homoectoine (4,5,6,7-tetrahydro-2-methyl-1H-(1,3)-diazepine-4-carboxylic acid), a synthetic derivative of ectoine, have beneficial effects during dextran sulfate sodium (DSS)-induced colitis in mice. METHODS/RESULTS: We found that the disease activity index was significantly reduced by both ectoines. DSS-induced edema formation, epithelial permeability, leukocyte recruitment and tissue damage were reduced by ectoine and homoectoine, with the latter having stronger effects. Interestingly, the claudin switch usually observed during colitis (decreased expression of claudin-1 and increased expression of the leaky claudin-2) was completely prevented by homoectoine, whereas ectoine only reduced claudin-2 expression. Concomitantly, only homoectoine ameliorated the drop in transepithelial electrical resistance induced by IFN-γ and TNF-α in Caco-2 cells. Both ectoines inhibited loss of ZO-1 and occludin and prevented IFN-γ/TNF-α-induced increased paracellular flux of 4 kDa FITC-dextran in vitro. Moreover, both ectoines reduced expression of pro-inflammatory cytokines and oxidative stress during colitis. CONCLUSION: While both ectoine and homoectoine have protective effects on the epithelial barrier during inflammation, only homoectoine completely prevented the inflammatory claudin switch in tight junctions. Thus, homoectoine may serve as diet supplement in IBD patients to reach or extend remission.