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Scientific Reports Dec 2022Novel polyelectrolytic hybrid membranes are prepared by blending carboxy methyl cellulose (CMC)-polyvinyl alcohol (PVA)-acrylamide (AA). Succinic acid and chlorosulfonic...
Novel polyelectrolytic hybrid membranes are prepared by blending carboxy methyl cellulose (CMC)-polyvinyl alcohol (PVA)-acrylamide (AA). Succinic acid and chlorosulfonic acid (CSA) are employed as crosslinkers and modifiers, respectively. Additionally, carboxylated carbon nanotube (CCNT) and sulfonated activated carbon (SAC) as fillers are used to attain appropriate chemical and mechanical stability for use as polyelectrolyte membranes (PEM). CMC, PVA, and AA are mixed and treated with CSA, CCNT, and SAC in different concentrations. First, CMC/PVA/AA solution is modified using CSA to produce a sulfonated polymeric matrix. Second, a different amount of CCNT or SAC was added as a filler to enhance the ion exchange capacity (IEC), ionic conductivity, and chemical stability. Third, the solution is cast as polyelectrolytic membranes. Chemical interactions between CMC, PVA, AA and other membrane components were confirmed using various characterization techniques such as Raman scattering spectroscopy and Fourier Transform Infrared (FTIR). Furthermore, mechanical strength, methanol uptake, gel fraction, ion exchange capacity (IEC), proton conductivity (PC), chemical and thermal stability were determined as functions of varied membrane modification components. Results reveal that the increase of CSA, CCNT and SAC is leading to increase the IEC values reaching 1.54 mmol/g for (CMC/PVA-4% CSA), 1.74 mmol/g for (CMC/PVA-4%CSA-2%CCNT) and 2.31 mmol/g for (CMC/PVA-4% CSA-2% SAC) comparing to 0.11 mmol/g for non-modified CMC/PVA/AA membrane. Sequentially, the proton conductivity value is changed from 1 × 10 S/cm in non-modified CMC/PVA/AA membrane to 0.082 S/cm for (CMC/PVA-4% CSA), 0.0984 S/cm for (CMC/PVA-4%CSA-2%CCNT) and 0.1050 S/cm for (CMC/PVA-4% CSA-2% SAC). Such results enhance the potential feasibility of modified CMC/PVA/AA hybrid as polyelectrolytic membranes.
Topics: Polyvinyl Alcohol; Polyelectrolytes; Acrylamide; Carboxymethylcellulose Sodium; Protons; Alkanesulfonates
PubMed: 36539477
DOI: 10.1038/s41598-022-26489-0 -
Bioorganic & Medicinal Chemistry Letters Sep 2020Heroin overdose and addiction remain significant health and economic burdens in the world today costing billions of dollars annually. Moreover, only limited...
Heroin overdose and addiction remain significant health and economic burdens in the world today costing billions of dollars annually. Moreover, only limited pharmacotherapeutic options are available for treatment of heroin addiction. In our efforts to combat the public health threat posed by heroin addiction, we have developed vaccines against heroin. To expand upon our existing heroin-vaccine arsenal, we synthesized new aryl and alkyl sulfonate ester haptens; namely aryl-mono-sulfonate (H) and Aryl/alkyl-di-sulfonate (H) as carboxyl-isosteres of heroin then compared them to our model heroin-hapten (H) through vaccination studies. Heroin haptens were conjugated to the carrier protein CRM and the resulting CRM-immunoconjugates were used to vaccinate Swiss Webster mice following an established immunization protocol. Binding studies revealed that the highest affinity anti-heroin antibodies were generated by the H vaccine followed by the H and H vaccines, respectively (H > H≫H). However, neither the H nor H vaccines were able to generate high affinity antibodies to the psychoactive metabolite 6-acetyl morphine (6-AM), in comparison to the H vaccine. Blood brain bio-distribution studies supported these binding results with vaccine efficiency following the trend H > H ≫ H The work described herein provides insight into the use of hapten-isosteric replacement in vaccine drug design.
Topics: Alkanesulfonates; Animals; Antibodies; Bacterial Proteins; Brain; Drug Design; Haptens; Heroin; Mice; Vaccines, Synthetic
PubMed: 32738981
DOI: 10.1016/j.bmcl.2020.127388 -
Environment International Feb 2023Epidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency and magnitude of this association remain unclear.
OBJECTIVE
The goal of this systematic review was to determine the size of the association between a doubling in perfluoroalkyl substances (PFAS) serum concentration and difference in log antibody concentration following a vaccine, with a focus on five PFAS: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA).
DATA SOURCE
We conducted online searches of PubMed and Web of Science through May 17, 2022 and identified 14 eligible reports published from 2012 to 2022.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
We included studies conducted in humans, including mother-child pairs, which examined serum PFAS concentration in relation to serum concentration of antibody to a specific antigen following a vaccine.
STUDY APPRAISAL AND SYNTHESIS METHODS
We used the risk of bias assessment for non-randomized studies of exposure and certainty assessment method proposed by Morgan et al. (2019). Using a multilevel meta-regression model, we quantitatively synthesized the data.
RESULTS
The 14 reports represented 13 unique groups of subjects; the frequency of studies of a given antibody was Tetanus (n = 7); followed by Diphtheria (6); Measles (4); Rubella (3); Haemophilus influenzae type b and Influenza A H1N1 (2 each); and Hepatitis A, Hepatitis B, Influenza A H2N3, Influenza B, and Mumps (1 each). There were approximately 4,830 unique participants included in the analyses across the 14 reports. The models of coefficients between antibody concentration and the five principal PFAS showed homogeneity of associations across antibody types for each principal PFAS. In the models with all antibodies treated as one type, evidence of effect modification by life stage was present for PFOA and PFOS, and for consistency, all associations were evaluated for all ages and for children. The summary associations (coefficients for difference in log[antibody concentration] per doubling of serum PFAS) with 95% confidence intervals that excluded zero ("statistical support"), and certainty of evidence ratings were as follows: for PFOA and all antibodies treated as one type in all ages, -0.06 (-0.10, -0.01; moderate) and in children, -0.10 (-0.16, -0.03; moderate); for Diphtheria in children, -0.12 (-0.23, -0.00; high); for Rubella in all ages, -0.09 (-0.17, -0.01; moderate), and for Tetanus in children, -0.12 (-0.24, -0.00; moderate). For PFOS the summary associations were, for all antibodies treated as one type in all ages, -0.06 (-0.11, -0.01; moderate) and in children, -0.10 (-0.18, -0.03; moderate); for Rubella in all ages, -0.09 (-0.15, -0.03; high) and in children, -0.12 (-0.20, -0.04; high). For PFHxS the summary associations were, for all antibodies treated as one type in all ages, -0.03 (-0.06, -0.00; moderate) and in children, -0.05 (-0.09, -0.00; low); and for Rubella in children, -0.07 (-0.11, -0.02; high). Summary associations for PFNA and PFDA did not have statistical support, but all PFAS studied tended to have an inverse association with antibody concentrations.
LIMITATIONS AND CONCLUSIONS
Epidemiologic data on immunosuppression and five principal PFAS suggest an association, with support across antibodies against multiple types of antigens. Data on Diphtheria, Rubella, and Tetanus were more supportive of an association than for other antibodies, and support was greater for associations with PFOA, PFOS, and PFHxS, than for PFNA or PFDA. The data on any specific antibody were scarce. Confounding factors that might account for the relation were not identified. Nearly all studies evaluated were judged to have a low or moderate risk of bias.
Topics: Humans; Infant, Newborn; Infant; Environmental Pollutants; Tetanus; Diphtheria; Influenza A Virus, H1N1 Subtype; Influenza, Human; Fluorocarbons; Vaccines; Alkanesulfonic Acids; Alkanesulfonates; Rubella
PubMed: 36764183
DOI: 10.1016/j.envint.2023.107734 -
Ecotoxicology and Environmental Safety Dec 2022Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to...
BACKGROUND
Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to adverse birth outcomes. However, the association between maternal exposure to PFASs and hemoglobin (Hb) and hematocrit (HCT) remains unclear.
OBJECTIVES
We aimed to explore the relationship between PFASs exposure with Hb and HCT during pregnancy.
METHODS
The present birth cohort study included 1044 pregnant women from Wuhan, China. Maternal HCT and Hb were measured in the first, second and third trimesters, and 13 PFASs were detected in the cord sera. Mixed linear models and general linear regression were applied to analyze the association between each single PFASs and Hb and HCT. Weighted quantile sum (WQS) regressions were used to investigate the association between PFASs mixture and Hb and HCT during pregnancy.
RESULTS
In single-PFAS models, 10 PFASs were positively associated with HCT and Hb across pregnancy (a 10-fold increase in PFASs was associated with 1.47-3.54 % change in HCT and 1.46-3.20 % change in Hb (All P-FDR < 0.05). In addition, Hb and HCT were more positively related to PFASs in the second and third trimesters rather than the first trimester. The association between PFASs exposure and maternal HCT and Hb was not significant in the iron supplementation group, whereas significant in the non-iron supplementation group. A significant interaction between iron supplementation and non-iron supplementation was also detected. WQS regressions showed that perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) contributed most to the association between PFASs and HCT and Hb in the second and third trimesters, respectively.
CONCLUSION
Maternal PFASs exposure was positive with serum Hb and HCT. Moreover, maternal iron supplementation may play a modifying effect in influencing the relationship between PFASs and HCT and Hb.
Topics: Pregnancy; Female; Humans; Hematocrit; Fluorocarbons; Cohort Studies; Hemoglobins; Alkanesulfonates
PubMed: 36423372
DOI: 10.1016/j.ecoenv.2022.114319 -
Journal of the American Chemical Society Mar 2020Photoactivation of bioactive molecules allows manipulation of cellular processes with high spatiotemporal precision. The recent emergence of visible-light excitable...
Photoactivation of bioactive molecules allows manipulation of cellular processes with high spatiotemporal precision. The recent emergence of visible-light excitable photoprotecting groups has the potential to further expand the established utility of the photoactivation strategy in biological applications by offering higher tissue penetration, diminished phototoxicity, and compatibility with other light-dependent techniques. Nevertheless, a critical barrier to such applications remains the significant hydrophobicity of most visible-light excitable photocaging groups. Here, we find that applying the conventional 2,6-sulfonation to -methyl BODIPY photocages is incompatible with their photoreaction due to an increase in the excited state barrier for photorelease. We present a simple, remote sulfonation solution to BODIPY photocages that imparts water solubility and provides control over cellular permeability while retaining their favorable spectroscopic and photoreaction properties. Peripherally disulfonated BODIPY photocages are cell impermeable, making them useful for modulation of cell-surface receptors, while monosulfonated BODIPY retains the ability to cross the cellular membrane and can modulate intracellular targets. This new approach is generalizable for controlling BODIPY localization and was validated by sensitization of mammalian cells and neurons by visible-light photoactivation of signaling molecules.
Topics: Alkanesulfonates; Animals; Boron Compounds; Cell Membrane; Dopamine; Drug Carriers; Fluorescent Dyes; HEK293 Cells; Hippocampus; Histamine; Humans; Light; Microscopy, Confocal; Microscopy, Fluorescence; Molecular Structure; Neurons; Rats; Solubility
PubMed: 32115942
DOI: 10.1021/jacs.9b13219 -
International Journal of Biological... Feb 2022The coimmobilization of lipases from Rhizomucor miehei (RML) and Candida antarctica (CALB) has been intended using agarose beads activated with divinyl sulfone. CALB...
The combination of covalent and ionic exchange immobilizations enables the coimmobilization on vinyl sulfone activated supports and the reuse of the most stable immobilized enzyme.
The coimmobilization of lipases from Rhizomucor miehei (RML) and Candida antarctica (CALB) has been intended using agarose beads activated with divinyl sulfone. CALB could be immobilized on this support, while RML was not. However, RML was ionically exchanged on this support blocked with ethylendiamine. Therefore, both enzymes could be coimmobilized on the same particle, CALB covalently using the vinyl sulfone groups, and RML via anionic exchange on the aminated blocked support. However, immobilized RML was far less stable than immobilized CALB. To avoid the discarding of CALB (that maintained 90% of the initial activity after RML inactivation), a strategy was developed. Inactivated RML was desorbed from the support using ammonium sulfate and 1% Triton X-100 at pH 7.0. That way, 5 cycles of RML thermal inactivation, discharge of the inactivated enzyme and re-immobilization of a fresh sample of RML could be performed. In the last cycle, immobilized CALB activity was still over 90% of the initial one. Thus, the strategy permits that enzymes can be coimmobilized on vinyl sulfone supports even if one of them cannot be immobilized on it, and also permits the reuse of the most stable enzyme (if it is irreversibly attached to the support).
Topics: Candida; Enzyme Stability; Enzymes, Immobilized; Fungal Proteins; Sulfones
PubMed: 34973984
DOI: 10.1016/j.ijbiomac.2021.12.148 -
Environment International Mar 2023Perfluoroalkyl substances (PFAS) are persistent and pose a risk to human health. High throughput screening (HTS) cell-based bioassays may inform risk assessment of PFAS...
Perfluoroalkyl substances (PFAS) are persistent and pose a risk to human health. High throughput screening (HTS) cell-based bioassays may inform risk assessment of PFAS provided that quantitative in vitro to in vivo extrapolation (QIVIVE) can be developed. The QIVIVE ratio is the ratio of nominal (C) or freely dissolved concentration (C) in human blood to C or C in the bioassays. Considering that the concentrations of PFAS in human plasma and in vitro bioassays may vary by orders of magnitude, we tested the hypothesis that anionic PFAS bind to proteins concentration-dependently and therefore the binding differs substantially between human plasma and bioassays, which has an impact on QIVIVE. Solid phase microextraction (SPME) with C18-coated fibers served to quantify the C of four anionic PFAS (perfluorobutanoate (PFBA), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS)) in the presence of proteins and lipid, medium components, cells and human plasma over five orders of magnitude in concentrations. The C18-SPME method was used to quantify the non-linear binding to proteins, human plasma and medium, and the partition constants to cells. These binding parameters were used to predict C of PFAS in cell bioassays and human plasma by a concentration-dependent mass balance model (MBM). The approach was illustrated with a reporter gene assay indicating activation of the peroxisome proliferator-activated receptor gamma (PPARγ-GeneBLAzer). Blood plasma levels were collected from literature for occupational exposure and the general population. The QIVIVE ratios were higher than the QIVIVE ratios due to the strong affinity to proteins and large differences in protein contents between human blood and bioassays. For human health risk assessment, the QIVIVE ratios of many in vitro assays need to be combined to cover all health relevant endpoints. If C cannot be measured, they can be estimated with the MBM and concentration-dependent distribution ratios.
Topics: Humans; Biological Availability; Protein Binding; Fluorocarbons; Alkanesulfonic Acids; Alkanesulfonates; Biological Assay; Environmental Pollutants
PubMed: 36881956
DOI: 10.1016/j.envint.2023.107857 -
Molecules (Basel, Switzerland) Dec 2016Sulfones are one of the most important classes of agricultural fungicides. To discover new lead compounds with high antibacterial activity, a series of new sulfone...
Sulfones are one of the most important classes of agricultural fungicides. To discover new lead compounds with high antibacterial activity, a series of new sulfone derivatives were designed and synthesized by introducing the aroxymethyl moiety into the scaffold of 1,3,4-oxadiazole/thiadiazole sulfones. Antibacterial activities against three phytopathogens (, , .) were assayed in vitro. As compared to the control of commercial fungicides and some reported sulfone fungicides, seven compounds - exerted remarkably higher activities with EC values ranging from 0.45-1.86 μg/mL against and 1.97-20.15 μg/mL against . Exhilaratingly, , and displayed significant in vivo activity against with protective effect of 90.4%, 77.7%, and 81.1% at 200 μg/mL, respectively, much higher than that exhibited by Bismerthiazol (25.6%) and Thiadiazole-copper (32.0%). And the differential phytotoxicity of active derivatives was preliminarily checked. The results demonstrated that derivative of 2-aroxymethyl-1,3,4-oxadiazole/thiadiazole sulfone can serve as potential alternative bactericides for the management of plant bacterial diseases.
Topics: Anti-Bacterial Agents; Drug Design; Microbial Sensitivity Tests; Oxadiazoles; Plant Diseases; Ralstonia solanacearum; Structure-Activity Relationship; Sulfones; Thiadiazoles; Xanthomonas
PubMed: 28042864
DOI: 10.3390/molecules22010064 -
Angewandte Chemie (International Ed. in... Oct 2022The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient...
The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient synthetic access, limiting the structural diversity of currently available sulfoxides. Here, we report a data-guided development of direct decarboxylative sulfinylation that enables the previously inaccessible functional group interconversion of carboxylic acids to sulfoxides in a reaction with sulfinates. Given the broad availability of carboxylic acids and the growing synthetic potential of sulfinates, the direct decarboxylative sulfinylation is poised to improve the structural diversity of synthetically accessible sulfoxides. The reaction is facilitated by a kinetically favored sulfoxide formation from the intermediate sulfinyl sulfones, despite the strong thermodynamic preference for the sulfone formation, unveiling the previously unknown and chemoselective radicalophilic sulfinyl sulfone reactivity.
Topics: Sulfoxides; Carboxylic Acids; Sulfones; Oxidation-Reduction; Metals
PubMed: 36006859
DOI: 10.1002/anie.202210525 -
Xenobiotica; the Fate of Foreign... Feb 2021We investigated the plasma toxicokinetic behavior of free (parent) and total (parent and conjugated forms) of bisphenol S (BPS) and bisphenol AF (BPAF) in plasma of...
We investigated the plasma toxicokinetic behavior of free (parent) and total (parent and conjugated forms) of bisphenol S (BPS) and bisphenol AF (BPAF) in plasma of adult male rats and mice following exposure via feed for 7 days to BPS (338, 1125, and 3375 ppm) or BPAF (338, 1125, and 3750 ppm). In rats, the exposure concentration-normalized maximum concentration [C/D (ng/mL)/(ppm)] and area under the concentration time curve [AUC/D (h × ng/mL)/(ppm)] for free was higher for BPS (C/D: 0.476-1.02; AUC/D: 3.58-8.26) than for BPAF (C/D: 0.017-0.037; AUC/D:0.196-0.436). In mice, the difference in systemic exposure parameters between free BPS (C/D: 0.376-0.459; AUC/D: 1.52-2.54) and free BPAF (C/D: 0.111-0.165; AUC/D:0.846-1.09) was marginal. Elimination half-lives for free analytes (4.41-10.4 h) were comparable between species and analogues. When systemic exposure to free analyte was compared between species, in rats, BPS exposure was slightly higher but BPAF exposure was much lower than in mice. BPS and BPAF were highly conjugated; total BPS AUC values (rats ≥18-fold, mice ≥17-fold) and BPAF (rats ≥127-fold, mice ≥16-fold) were higher than corresponding free values. Data demonstrated that there are analogue and species differences in the kinetics of BPS and BPAF.
Topics: Animals; Benzhydryl Compounds; Hazardous Substances; Kinetics; Male; Mice; Phenols; Rats; Sulfones; Toxicity Tests; Toxicokinetics
PubMed: 32985913
DOI: 10.1080/00498254.2020.1829171