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Methylthionine Chloride (MTC), commonly known as methylene blue, is a substance widely used in medical and clinical industry as indicator, various diseases treatment and diagnostic. When MTC is discarded out of the organism, it becomes a residue which ends in wastewater treatment plants and it is not treated or removed properly because it has a synthetic origin, providing it with stability and chemical structure difficult to break. In the present work, MTC was treated through advanced oxidation processes (AOPs) photolysis and heterogeneous photocatalysis, in three pH magnitudes (3.5, 7.2 and 9.5), and comparing when 1 mMol of H2O2/L of sample was added or not at the beginning of the experiment. MTC degradation reached 62.9 and 54.14%, for photolysis and photocatalysis respectively, both in acid pH conditions and adding H2O2 to the sample. Kinetic constants (K) were calculated, showing acid pH as more effective; likewise, half life time decreases under these conditions. With Student-t statistic test, K from both processes were compared, resulting acidic and basic pH significantly different, but not neutral.

Background: In the therapy of cancer, several treatments have been designed using nanomaterials, among which gold nanoparticles (AuNPs) have been featured as a promising antitumoral agent. Our research group has developed the synthesis of gold nanoparticles L-AuNPs and D-AuNPs stabilized with zwitterions of imidazolium (L-1 and D-1) derived from L-methionine and D-methionine. Because the stabilizer agent is chiral, we observed through circular dichroism that AuNPs also present chirality; such chirality as well as the fact that the stabilizing agent contains fragments of methionine and imidazolium that are commonly involved in biological processes, opens up the possibility that this system may have biological compatibility. Additionally, the presence of methionine in the stabilizing agent opens the application of this system as a possible antitumor agent because methionine is involved in methylation processes of molecules such as DNA. Objective: The aim of this research is the evaluation of the antitumor activity of gold nanoparticles stabilized with zwitterions of imidazolium (L-AuNPs) derived from L-methionine in the model of BALB/c mice with lymphoma L5178Y. Methods: Taking as a parameter cell density, the evaluation of the inhibitory effect of L-AuNPs was carried out with a series of in vivo tests in BALB/c type mice; three groups of five mice each were formed (Groups 1, 2 and 3); all mice were i.p. inoculated with the lymphoblast murine L5178Y. Group 1 consisted of mice without treatment. In the Groups 2 and 3 the mice were treated with L-AuNPs at 0.3 mg/Kg on days 1, 7 and 14 by orally and intraperitonally respectively. Results: These results show low antitumor activity of these gold nanoparticles (L-NPsAu) but interestingly, the imidazolium stabilizing agent of gold nanoparticle (L-1) displayed promising antitumor activity. On the other hand, the enantiomer of L-1, (D-1) as well as asymmetric imidazole derivate from L-methionine (L-2), do not exhibit the same activity as L-1. Conclusion: The imidazolium stabilizing agent (L-1) displayed promising antitumor activity. Modifications in the structure of L-1 showed that, the stereochemistry (like D-1) and the presence of methionine fragments (like L-2) are determinants in the antitumor activity of this compound.

PURPOSE This study evaluated the bone-forming potential of the demineralized human dentin matrix by performing histologic and morphometric analyses. The immunolabeling of osteopontin, a determinant protein for bone repair, was also evaluated. MATERIALS AND METHODS Wistar rats were selected and submitted to the extraction of the right and left second molars. Tooth sockets were separated into two groups: the control group (right), which was filled with the blood clot, and the experimental group (left), which was filled with demineralized human dentin matrix. Animals were sacrificed at 5, 10, and 21 days. Histologic and histoquantitative analyses (analyses of variance [ANOVA] and Tukey's test) were performed, as well as immunostaining for osteopontin as an osteogenesis indicator. RESULTS After 5 days, demineralized human dentin matrix was incorporated by new trabeculae. After 10 days, connective tissue organization and new trabeculae were observed in the experimental group, and intense staining for osteopontin close to demineralized human dentin matrix was observed in the experimental group. After 21 days, the experimental group was showing mature trabeculae. A statistical difference was observed (P < .05). There was a higher number of trabeculae in the experimental groups in all periods of analysis. The presence of osteopontin was observed more intensely at 10 days close to demineralized human dentin matrix. CONCLUSION This study indicates that demineralized human dentin matrix implanted in tooth sockets induces the acceleration of osteogenesis.

In this work, we have explored the use of hydrophobic deep eutectic systems (DESs) composed of D-L-menthol and different naturally occurring acids (acetic acid, lauric acid, lactic acid and pyruvic...

Acholeplasma (A.) laidlawii is an opportunistic pathogen with the ability to disseminate resistance determinants to antibiotics, however, its resistance to macrolides has been less studied. The aim of the present study was to characterize the mechanisms responsible for the resistance to macrolides, tiamulin and lincomycin found in a strain of A. laidlawii isolated from a pig with pneumonia. MICs of erythromycin, 15- and 16-membered macrolides, tiamulin and lincomycin were determined by microdilution method with and without reserpine, an inhibitor of ABC efflux pumps and regions of the genome were sequenced. Reserpine only decreased lincomycin MIC but it did not change the MICs of macrolides and tiamulin. The analysis of the DNA sequence of 23S rRNA showed nucleotide substitutions at eight different positions, although none of them were at positions previously related to macrolide resistance. Five mutations were found in the L22 protein, one of them at the stop codon. In addition, two mutations were found in the amino acid sequence of L4. The combination of multiple mutations in the ribosomal proteins L22 and L4 together with substitutions in 23S rRNA DNA sequence was associated with the resistance to macrolides, the pleuromutilin and lincomycin in the studied A. laidlawii strain.

SUMMARYThe conserved MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates and invertebrates. Whether and how JIP3’s interaction with dynein and kinesin-1 contributes to this critical organelle clearance function is unclear. Using purified recombinant human proteins, we show that dynein light intermediate chain (DLIC) binds to the N-terminal RH1 domain of JIP3, its paralog JIP4, and the lysosomal adaptor RILP. A point mutation in a hydrophobic pocket of the RH1 domain, previously shown to abrogate RILPL2 binding to myosin Va, abrogates the binding of JIP3/4 and RILP to DLIC without perturbing the interaction between the JIP3 RH1 domain and kinesin heavy chain. Characterization of this separation-of-function mutation in Caenorhabditis elegans shows that JIP3–bound dynein is required for organelle clearance in the anterior process of touch receptor neurons. Unlike JIP3 null mutants, JIP3 that cannot bind DLIC causes prominent accumulation of endo-lysosomal organelles at the neurite tip, which is rescued by a disease-associated point mutation in JIP3’s leucine zipper that abrogates kinesin light chain binding. These results highlight that RH1 domains are interaction hubs for cytoskeletal motors and suggest that JIP3–bound dynein and kinesin-1 participate in bi-directional organelle transport.

Groundwater samples from a mining community north of Mexico were studied, concentration of metals above the maximum allowable concentration from Mexican regulation were found. Spherical agglomeration technique (SAT) was used to remove metals (Pb, Cu, Cr, Ni, Zn, Mn, Cd). Two precipitating agents were tested: NaOH and Ca(OH)2. Also, Agave tequilana Weber extract as hydrophobicizing agent was employed to avoid metal redisolution. High metal removal proved the effectiveness on SAT application under a pH ranging between 9 and 11 and extract doses from 0.3 g extract/g pollutant. Better removal percentages were reached when using Ca(OH)2 as precipitating. Reported removal efficiency in that case yielded removal percentages as high as 99% removal for Pb under the three pH tested. The heavy metal evaluation index before treatment was 2354.91, but decreased to levels as low as 4.7 after SAT application.

Aqueous 2,5-dichlorophenol (2,5-DCP) degradation was studied. Degradation was performed by solar photolysis and heterogeneous photocatalysis on TiO2 synthesized by sol-gel method. A thin film solar reactor of 1 m2 surface area was used. Solution was recirculated for 30 min under a laminar regime, with 20° and 26° surface slopes, under different temperatures and radiation. Samples were taken every 5 min to determine chemical oxygen demand (COD) and absorbance at λ= 280 nm. A 23 factorial with covariates and repeated measures experimental design was used to determine degradation kinetics of 2,5-DCP in short reaction times, having two response variables: COD and concentration of 2,5-DCP, determined at 280 nm. The factors were: reactor inclination angles (20° and 26°), flow (355 L/h and 407 L/h) and process (photolysis and photocatalysis); and covariates: solar radiation, temperature, evaporation and initial concentration of 2,5-DCP. By comparing the kinetic constants of both processes using Student-t statistic, significant differences (p

Disulfiram (DSF) can help treat alcohol dependency by inhibiting aldehyde dehydrogenase (ALDH). Genomic analysis revealed that Francisella tularensis, the causative agent of tularemia, has lost all but one ALDH-like domain and that this domain retains the target of DSF. In this study, minimum inhibitory concentration (MIC) assays demonstrated that both DSF and its primary metabolite diethyldithiocarbamate (DDC) have strong antimicrobial activity against F. tularensis strain SCHU S4, with the MIC of DSF determined as 2 µg/mL in comparison with 8 µg/mL for DDC. The activity of DSF was further confirmed using an in vitro human macrophage infection assay. Francisella tularensis bacteria in DSF-treated cells were reduced in comparison with untreated and DDC-treated cells, comparable with that observed in doxycycline-treated cells. This suggests that DSF may be suitable for further investigation as an in vivo therapy for tularemia.

At a key moment when education systems are moving towards the development of 21st-century skills at school, we propose to develop them with a series of enquiry activities connected to the real world on the subject of Chemistry in Compulsory Secondary Education. The four selected topics have practical aspects, as they are related to industrial chemistry, and are proposed in educational practice using the 5E model. The results obtained in a pilot test with 22 students show that the context created facilitates the development of 21st century competences. It is understood that this novel proposal can be successfully employed in other contexts.

Background: In 2020 the composition and procedure to elaborate a new formulation containing Isoniazid, Pyrazinamide and Rifampicin to treat tuberculosis in pediatric patients was published. The temperature and relative humidity in Tuberculosis-endemic countries are high, > 30ºC and > 70% respectively and thus these meteorological conditions required a new dosage form. The objective of this work is to register changes in tablet quality and stability over time when exposed to different storage conditions according to ICH. Method: Tablets were subjected to accelerated, long term and low relative humidity conditions. The effect of light was also tested. Quality was measured by evaluating weight changes tensile strength, disintegration time, and drug content. Hydrazine formation was also evaluated as it is considered a mutagenic degradation product. Results: Tablets stored at low relative humidity showed the best stability. There was no statistically significant difference between tablets exposed to or protected from light. Moreover, the formation of Hydrazine was not detected during stability studies. Conclusion: This new dosage form for treating Tuberculosis is stable and able to maintain its quality when appropriate storage conditions are used.

[EN] The inactivation processes of coliform bacteria (total and fecal) and sulphito-reducing Clostridium bacteria (vegetative species and spores) in water maturation lagoon of a low-cost nature-based wastewater treatment plant using constructed wetlands and through processes of photolysis in a pilot photoreactor have been comparatively studied. The diferent inactivation mechanisms by photolysis of these bacteria have been studied following the criteria of diferent statistical and kinetic models. Clostridium disinfection treatments ft models in which two types of bacteria populations coexist, one sensitive (vegetative species) and the other (spores) resistant to the treatment, the sensitive one (94%) with an inactivation rate of k=0.24±0.07 min−1 and the resistant one (6%) with k=0.11±0.05 min−1. Total coliform photolytic disinfection also shows two populations with diferent physiological state. The time required to reduce the frst logarithmic decimal cycle of the diferent types of bacteria (physiological states) are δ1=4.2±0.9 and δ2=8.3±1.1 min, respectively. For fecal coliform photolytic disinfection, only bacteria population, with k=1.15±0.19 min−1, is found. The results obtained confrm the photolytic disinfection processes and maturation lagoon are efective systems for Clostridia bacteria removal after water treatment by nature-based systems. Total removal of coliform bacteria is not achieved by maturation lagoons, but their reduction is signifcant using low doses of cumulative radiation., Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE.

TiO2 is a photocatalyst widely used for the degradation of organic compounds in aqueous media; however, it presents some difficulties for application on larger scales. The biggest limitations are its bandgap value of 3.2 eV which corresponds to the UV range of the spectrum and its difficult removal from the reaction medium after the reaction. An alternative to enhance the photocatalytic activity of TiO2 consists in design heterojunctions with semiconductors that are active under visible light irradiation. Some reports have described the magnetic property and synthesis procedures based on inexpensive and abundant raw material. In this work, we synthesized photocatalysts based on γ-Fe2O3impregnated with different levels of TiO2. This may contribute to improving the wide application of TiO2 in water, since γ-Fe2O3 has magnetic features that facilitate the removal of the catalyst after the reaction run. The materials were characterized by X-ray diffraction, analysis of adsorption/desorption of N2, reflectance diffuse, and 57Fe Mossbauer spectroscopy. The photocatalytic activity of the materials was tested for removing rhodamine under visible or visible light in the presence of H2O2. From the X-ray diffraction and 57Fe Mossbauer spectroscopy data, it was observed the formation of γ-Fe2O3 phase with small particle. Without visible light, only 45% of RhB was adsorbed, and with the light on, there is no increase in removal after 60 min. However, after adding H2O2, the photocatalytic activity of material was significantly improved, reaching 80% of dye removal. Tests using scavengers of reactive species revealed that −O2 and ․OH are the main species in this system. Moreover, the H2O2 retards the electron-hole recombination, thus increasing its photocatalytic activity. The ESI-MS analysis revealed that in 15 min of reaction, deethylation (m/z = 415, 388), deamination (m/z = 301 and 279), and rhodamine B severe oxidation products (m/z

Background Mycoplasma (M.) hyopneumoniae, M. hyorhinis and M. hyosynoviae are significant pathogens for the porcine industry worldwide. The aim of the present study was to determine the antimicrobial susceptibility of six key antimicrobials (tylosin, tilmicosin, tylvalosin, lincomycin, tiamulin and valnemulin) routinely used for treating infections caused by these pathogens. Twenty-seven M. hyopneumoniae, 48 M. hyorhinis and 40 M. hyosynoviae field strains isolated from clinical samples from different Southern European countries between 2013 and 2018 using broth microdilution method were evaluated. Results Tylvalosin exhibited the highest in vitro activity among the macrolides assayed, with MIC90 values 4 to 5 two-fold dilutions lower than those of tylosin and tilmicosin. The pleuromutilin valnemulin showed one of the highest in vitro activities against the three mycoplasma species. On the contrary, lincomycin exhibited the highest MIC values of the antimicrobials tested. Conclusions The data obtained in the present study supports the use of pleuromutilins and macrolides for the control of infections caused by porcine mycoplasmas. The use of lincomycin for the treatment of porcine mycoplasma infections should be carefully evaluated due to the presence of circulating field isolates with decreased susceptibility to this antimicrobial.

Cyanobacteria are ubiquitous organisms with a relevant contribution to primary production in all range of habitats. Cyanobacteria are well known for their part in worldwide occurrence of aquatic blooms while producing a myriad of natural compounds, some with toxic potential, but others of high economical impact, as geosmin. We performed an environmental survey of cyanobacterial soil colonies to identify interesting metabolic pathways and adaptation strategies used by these microorganisms and isolated, sequenced and assembled the genome of a cyanobacterium that displayed a distinctive earthy/musty smell, typical of geosmin, confirmed by GC-MS analysis of the culture’s volatile extract. Morphological studies pointed to a new Oscillatoriales soil ecotype confirmed by phylogenetic analysis, which we named Microcoleus asticus sp. nov. Our studies of geosmin gene presence in Bacteria, revealed a scattered distribution among Cyanobacteria, Actinobacteria, Delta and Gammaproteobacteria, covering different niches. Careful analysis of the bacterial geosmin gene and gene tree suggests an ancient bacterial origin of the gene, that was probably successively lost in different time frames. The high sequence similarities in the cyanobacterial geosmin gene amidst freshwater and soil strains, reinforce the idea of an evolutionary history of geosmin, that is intimately connected to niche adaptation.

The main challenge for partial nitrification is to reach stable nitrite accumulation, which strongly depends on the nitrite-oxidizing bacteria (NOB) growth in the reactor. The on-line estimation of active biomass may enhance the decision-making process to maintain a high nitrite accumulation in the reactor. In this work, we propose an active biomass estimator based on ASM1 and on-line oxygen uptake rate measurements (OUR-E) in a sequencing batch reactor. In order to validate the OUR-E, two operating scenarios were applied during 200 days of operation: unfavorable (sludge retention time (SRT) = 40 d, pH = 7.6, dissolved oxygen (DO) = 2 mg/L) and favorable for partial nitrification (SRT = 10 d, pH = 8.5, DO = 2 mg/L). Furthermore, a second estimation method based on off-line measurements of N-species concentrations (Nsp-E) was implemented to evaluate the performance of the OUR-E. The OUR-E was able to predict a reduction in the NOB active fraction from 10.3% to 1.6% with nitrite accumulation over 80% when we shifted the operating scenario. Although both estimators predicted similar results, the OUR-E showed a better prediction quality than the Nsp-E, according to Theil’s coefficient of inequality.

BackgroundMDR bacterial infections are currently a serious problem for clinicians worldwide. Klebsiella pneumoniae and Enterobacter spp., among Enterobacteriaceae, and Pseudomonas aeruginosa, are part of the group of ESCAPE pathogens or bacteria that ‘escape’ from common antibacterial treatments. The lack of effectiveness of the first common line of antibiotics has led to the search for new therapies based on older antibiotics, such as colistin.ObjectivesWe searched for new enhancers of the action of colistin against MDR Gram-negative bacteria that can be easily applicable to clinical treatments.MethodsColistin MICs were determined alone and with the protonophores CCCP, sodium benzoate, sodium salicylate and aspirin using the broth microdilution method and FIC indexes were calculated to assess synergy between colistin and each chemical. Time–kill assays of colistin with and without protonophores were performed to determine the bactericidal action of combinations of colistin with protonophores. Likewise, the effect of sucrose, l-arginine and l-glutamic acid on the MICs of colistin alone and combined with each protonophore was assessed.ResultsIt was found that sodium benzoate, sodium salicylate and aspirin, at concentrations allowed for human and animal use, partially or totally reversed resistance to colistin in P. aeruginosa and highly resistant enterobacterial strains. The mechanism of action could be related to their negative charge at a physiological pH along with their lipid-soluble character.ConclusionsSodium benzoate, sodium salicylate and aspirin are good enhancers to use in antibiotic therapies that include colistin.

Escherichia coli (E. coli) and total coliforms (TC) present in biologically treated municipal wastewater were inactivated in samples from a wastewater treatment plant in Salamanca, Spain, through two advanced oxidation processes: UV-C/H2O2 photolysis and UV-C/(TiO2/SiO2)/H2O2 heterogeneous photocatalysis. A stainless steel reactor and a 40-W lamp (254 nm) were used. A 2 × 3 × 2 factorial design with covariates and repeated measures was performed, with the factors: initial pH of the sample (6, 7.5 and 9) and dose of H2O2 (0 and 0.5 mmol/L). The kinetic analysis showed a first order reaction for the E. coli and TC inactivation. The highest inactivation rate constants, 0.523 min−1 for E. coli and 0.337 min−1 for TC, obtained in this work, correspond to experiments performed by UV-C/(TiO2/SiO2) photocatalysis, with initial pH 6 and 0.5 mM of H2O2/L; under these conditions, the time of total inactivation of E. coli and TC microorganisms was 10 and 20 min, respectively. The analysis of covariance confirms that after three min of the experiment, all considered parameters are significant (p

In this paper we describe a simple reproducible in vitro method to study the diffusion of two different drugs with varying physico-chemical properties from two thermosensitive biocompatible polymeric hydrogels. This system enabled characterization of the in vitro diffusion mechanism of triamcinolone and bone morphogenetic protein-2 from pluronic and from composite hyaluronic acid-pluronic hydrogels in gellan that simulates the in vivo environment. By this method we determined critical factors involved in the modulation of the drug diffusion from these controlled release devices, which allowed us to modulate the drug-release profile and simulate in vivo drug behavior.

PLGA (poly(lactic-co-glycolic) acid)-PEG (polyethylene glycol)-PLGA synthesis conditions have an impact on the physicochemical features of the copolymer and its usefulness as biomaterial. This study reports on an analysis of the composition and structural properties of PLGA-PEG-PLGA copolymers applying a variety of analytical techniques. Viscoelastic properties and particularly the temperature-responsive behavior of PLGA-PEG-PLGA showed a marked dependence on copolymer structural features. Physicochemical and biological properties, such as bioadhesion, biocompatibility and cell viability, of the raw copolymers and their gels were also evaluated. The most promising copolymer was chosen to formulate the osteoinductive protein bone morphogenetic protein-2 (125I-BMP-2), and the ability of its gels to sustain the release both in vitro and in vivo was monitored in situ using a gamma counter. In vitro diffusion studies were carried out using a bioinspired set-up that included a biorelevant receptor medium. In vivo release tests after implantation in a critical-size calvarial defect model showed an important burst, but then the release fitted well to the square-root kinetics. Importantly, the release rate constants recorded in vitro and in vivo matched each other suggesting close in vitro–in vivo correlation. Overall, the information gathered opens new perspectives in the biomedical application of these temperature-sensitive materials.

(1) Background: First-line antituberculosis treatment in paediatrics entails the administration of Isoniazid, Pyrazinamide, and Rifampicin. This study examines the possibility of developing a combined dose liquid formulation for oral use that would facilitate dose adjustment and adherence to treatment for younger children. (2) Methods: The active pharmaceutical ingredients stability under in vitro paediatric digestive pH conditions have been checked. The samples were studied as individual or fixed combined paediatric dosages to determine the pH of maximum stability. The use of hydroxypropyl-&beta, cyclodextrin to improve Rifampicin solubility and the use of ascorbic acid to increase the stability of the formulation have been studied. (3) Results: Maximum stability of combined doses was determined at pH 7.4, and maximum complexation at pH 8.0. Taking this into account, formulations presented the minimum dose of two active pharmaceutical ingredients dissolved. The addition of ascorbic acid at 0.1% w/v enables the detection of a higher remaining quantity of both drugs after three days of storage at 5 &deg, C. (4) Conclusions: a formulation which combines the minimum paediatric dosages dissolved recommended by WHO for Isoniazid and Rifampicin has been developed. Future assays are needed to prolong the stability of the formulation with the aim of incorporating Pyrazinamide to the solution.

The crystallographic properties of two titanium dioxide (TiO2) photocatalysts, P25, and commercial C1-TiO2 reactive grade, were analyzed by X-ray diffraction (XRD) and the band-gap was calculated with UV&ndash, Vis spectrometry with integration sphere. Then, their performance was tested in the degradation of 6-mercaptopurine (6-MP) by heterogeneous photocatalysis with solar radiation under different pH conditions and the addition of hydrogen peroxide (H2O2), the degradation efficiency was monitored by UV&ndash, Vis spectrophotometry. The XRD analysis showed that both photocatalysts studied have anatase phase, while only P25 contains rutile, the band gap values were lower, in both catalysts, than those reported for catalysts obtained by the sol-gel method. With both photocatalysts, degradation experiments showed efficiency greater than 98% in experiments in the presence of H2O2 regardless of pH. The properties of the photocatalysts, along with the data obtained from the experimentation, helped determine the best semiconductor for the degradation of 6-MP with these operating conditions in this work.

Sterilization is a quite challenging step in the development of novel polymeric scaffolds for regenerative medicine since conventional sterilization techniques may significantly alter their morphological and physicochemical properties. Supercritical (sc) sterilization, i.e. the use of scCO2 as a sterilizing agent, emerges as a promising sterilization method due to the mild operational conditions and excellent penetration capability. In this work, a scCO2 protocol was implemented for the one-pot preparation and sterilization of poly(-caprolactone) (PCL)/poly(lactic-co-glycolic acid) (PLGA) scaffolds. The sterilization conditions were established after screening against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) vegetative bacteria and spores of Bacillus stearothermophilus, Bacillus pumilus and Bacillus atrophaeus. The transition from the sterilization conditions (140 bar, 39 °C) to the compressed foaming (60 bar, 26 °C) was performed through controlled depressurization (3.2 bar/min) and CO2 liquid flow. Controlled depressurization/pressurization cycles were subsequently applied. Using this scCO2 technology toolbox, sterile scaffolds of well-controlled pore architecture were obtained. This sterilization procedure successfully achieved not only SAL-6 against well-known resistant bacteria endospores but also improved the scaffold morphologies compared to standard gamma radiation sterilization procedures This work was supported by Xunta de Galicia [ED431F 2016/01, ED431C 2020/17], MCIUN [RTI2018-094131-A-I00], MINECO [SAF2017-83118-R], Consellería de Sanidade, Servizo Galego de Saúde, Axencia de Coñecemento e Saúde (ACIS, CT850A-G), Agencia Estatal de Investigación [AEI] and FEDER funds. V. Santos-Rosales acknowledges to Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) for a predoctoral research fellowship [ED481A-2018/014]. C.A. García-González acknowledges to MINECO for a Ramón y Cajal Fellowship [RYC2014-15239] SI

Autophagy is an intracellular recycling process active in eukaryotic cells which involves the formation of an autophagosome that delivers cytoplasmic components to the lysosome for degradation. This process occurs at low rates under basal conditions, but it can be induced by diverse stress conditions such as starvation, hypoxia or metabolic disorders. Autophagic flux can also be enhanced in response to hormones, including leptin. Leptin is considered a pro-tumorigenic protein whose circulating levels have been related to a bad prognosis in obese breast cancer patients. It has been recently demonstrated that leptin can induce autophagy in cancer cell lines from different tissues, suggesting that autophagy could modulate the pro-tumorigenic effects associated with leptin. In this study, the role of autophagy in leptin-induced proliferation, migration, apoptosis and ERK phosphorylation in breast cancer cell lines was evaluated. Methods: MCF7 estrogen receptor positive and MDA-MB-231 triple negative breast cancer cell lines were used. MCF7 and MDA-MB-231 cell lines were stimulated with 400 and 50 ng/ml of leptin, respectively. Autophagy was assessed by LC3-II and p62 protein levels by western blot, and autophagosome formation by fluorescence microscopy. Proliferation and migration were assessed by real-time microscopy in an IncuCyte analyzer; and cell death was evaluated by fluorescence analysis of caspase activity. Changes in ERK phosphorylation were measure by western blot. Results: Leptin increased autophagy in MCF7 cells but not in triple negative MDA-MB-231 cells. In MCF7 cells, autophagy inhibition reduced leptin-induced cell proliferation, changes associated to a mesenchymal morphology, cell migration, and ERK activation. In MDA-MB-231 cells, autophagy inhibition reduced proliferation and increased apoptosis independently of leptin treatment. In both cell lines, leptin-induced migration and ERK phosphorylation were reduced by the inhibition of autophagy. Conclusion: Autophagy was important for increased cancer cell migration induced by leptin and for the maintenance of ERK phosphorylation. Our data suggest a potential use for the inhibition of autophagy in breast cancer associated with obesity. Citation Format: Alin García Miranda, Karen A. Solano Alcalá, José B. Montes Alvarado, Julio Reyes Leyva, Paola Maycotte, Eduardo Castañeda Saucedo. Autophagy mediates leptin induced migration and erk activation in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1940.

6-Mercaptopurine (6-MP) is a commonly used cytostatic agent, which represents a particular hazard for the environment because of its low biodegradability. In order to degrade 6-MP, four processes were applied: Photolysis (UV-C), photocatalysis (UV-C/TiO2), and their combination with H2O2, by adding 3 mM H2O2/L (UV-C/H2O2 and UV-C/TiO2/H2O2 processes). Each process was performed with variable initial pH (3.5, 7.0, and 9.5). Pilot scale reactors were used, using UV-C lamps as radiation source. Kinetic calculations for the first 20 min of reaction show that H2O2 addition is of great importance: in UV-C experiments, highest k was reached under pH 3.5, k = 0.0094 min−1, while under UV-C/H2O2, k = 0.1071 min−1 was reached under the same initial pH, similar behavior was observed for photocatalysis, as k values of 0.0335 and 0.1387 min−1 were calculated for UV-C/TiO2 and UV-C/TiO2/H2O2 processes, respectively, also under acidic conditions. Degradation percentages here reported for UV-C/H2O2 and UV-C/TiO2/H2O2 processes are above 90% for all tested pH values. Ecotoxicity analysis of samples taken at 60 min in the photolysis and photocatalysis processes, suggests that contaminant degradation by-products present higher toxicity than the original compound.

Heterogeneous catalysts that can absorb light over the solar range are ideal for green photocatalysis. Recently, attention has been directed towards the generation of novel solar-light photocatalysts, in particular, metal-free polymers. Herein, it is demonstrated that a metal-free, nonconjugated, anthraquinone-based copolymer (poly[1,4-diamine-9,10-dioxoanthracene-alt-(benzene-1,4-dioic acid)] (COP)) with a strong absorption in the visible region is effective as a sunlight heterogeneous photocatalyst. As a proof of concept, it has been used to mineralize 2,5-dichlorophenol (2,5-DCP) in water under air and sunlight irradiation. The photocatalytic efficiency of COP compares well with that of TiO2 -P25 when the reaction is carried out in a solar photoreactor in acid medium. Steady-state and time-resolved (absorption and emission) studies performed on COP suspended in 6:4 DMF/H2 O have provided valuable information about the COP species generated under different pH conditions. Steady-state absorption and fluorescence data are consistent with the existence of a tautomeric equilibrium between the 9,10-keto and 1,10-iminoketo quinoid forms for the anthraquinone in the ground state. Moreover, in basic media, transient absorption measurements showed the presence of two bands ascribed to the tautomeric triplet excited states, whereas only one of the triplets was observed in acid medium. A mechanism for the photocatalyzed degradation of 2,5-DCP by COP is proposed on the basis of these observations.

Dense and homogeneous metal-organic framework (MOF) coatings on functional bead surfaces are easily prepared by using intermediate sacrificial metal oxide coatings containing the metal precursor of the MOF. Polystyrene (PS) beads are coated with a ZnO layer to give ZnO@PS core-shell beads. The ZnO@PS beads are reactive in the presence of 2-methylimidazole to transform part of the ZnO coating into a porous zeolitic imidazolate framework-8 (ZIF-8) external shell positioned above the internal ZnO precursor shell. The obtained ZIF-8@ZnO@PS beads can be easily packed in column format for flow-through applications, such as the solid-phase extraction of trace priority-listed environmental pollutants. The prepared material shows an excellent permeance to flow when packed as a column to give high enrichment factors, facile regeneration, and excellent reusability for the extraction of the pollutant bisphenol A. It also shows an outstanding performance for the simultaneous enrichment of mixtures of endocrine disrupting chemicals (bisphenol A, 4-tert-octylphenol and 4-n-nonylphenol), facilitating their analysis when present at very low levels (1 μg L(-1) ) in drinking waters. For the extraction of the pollutant bisphenol A, the prepared ZIF-8@ZnO@PS beads also show a superior extraction and preconcentration capacity to that of the PS beads used as precursors and the composite materials obtained by the direct growth of ZIF-8 on the surface of the PS beads in the absence of metal oxide intermediate coatings.

Size exclusion chromatography (SEC) with different detection modes was assessed as a means to characterize the type of bevacizumab aggregate that forms under thermal stress, quantitatively monitoring the aggregation kinetics. The combination of SEC with light-scattering (SEC/LS) detection was validated using in-study validation process. This was performed by applying a strategy based on a control chart to monitor the process parameters and by inserting quality control samples in routine runs. The SEC coupled with a differential refractive-index detector (SEC/RI) was validated using a pre-study validation process in accordance with the ICH-Q2 (R1) guidelines and in-study monitoring in accordance with the Analytical Target Profile (ATP) criteria. The total error and β-expectation tolerance interval rules were used to assess method suitability and control the risk of incorrectly accepting unsuitable analytical methods. The aggregation kinetics data were interpreted using a modified Lumry-Eyring model. The true order of the reaction was determined using the initial-rate approach. All the kinetic data show a linear Arrhenius dependence within the studied temperature range. The Arrhenius approach over-predicted the aggregation rate for 5°C, but provides an idea of the aggregation process and amount of aggregate formed. In any case, real-time stability data are necessary to establish the product shelf-life.

A series of activated carbons (ACs) were prepared by modifying a commercial AC by physical activation using CO2 during different activation times. The ACs were designated as F, F12, F24, and F40 corresponding to the activation times of 0, 12, 24, and 40 h, respectively. The surface area, total pore volume, micropore volume, and mean micropore width were determined for all the ACs. The textural properties of the modified ACs increased substantially with the activation time, and the capacity of the ACs for adsorbing diclofenac (DCF) was almost linearly dependent upon the surface area of the ACS. The maximum adsorption capacities of F, F12, F24, and F40 carbons towards diclofenac (DCF) from aqueous solution were 271, 522, 821, and 1033 mg/g, respectively. Hence, the adsorption capacities of ACs were considerably enhanced with the activation time, and F12, F24, and F40 carbons presented the highest adsorption capacities towards DCF reported in the technical literature. The F40 adsorption capacity was at least twice those of other carbon materials. The adsorption capacities decreased by raising the pH from 7 to 11 due to electrostatic repulsion between the ACs surface and anionic DCF in solution. The removal of DCF from a wastewater treatment plant (WWTP) effluent was effectively carried out by adsorption on F40. Hence, the capacity of ACs for adsorbing DCF can be optimized by tailoring the porous structure of ACs., This work was supported by Consejo Nacional de Ciencia y Tecnologia, CONACyT, Mexico (grants numbers INFR-2012-01-188381 and CB-2012-02-182779). COA and JBP thank the support of the Spanish MINECO (grant number CTM2014/56770-R).

Stable molecular hydrogen isotopes, D and T, are both scarce and essential in several energy, industrial, and large-scale fundamental research applications. Due to the chemical similarity of these isotopes, their extraction and purification from hydrogen has relied for decades on expensive and energy-demanding processes. However, factoring in the phenomenon of quantum sieving could provide a new route for these separations. In this work, we have explored how to separate hydrogen isotopes by adsorption taking these quantum effects into account. To this end, we have conducted adsorption measurements to test our deuterium model and performed a widespread computational screening over 210 pure-silica zeolites for D/H and T/H separations. Based on low-coverage adsorption properties, a reduced set of zeolites have been singled out and their performance in terms of adsorption capacity, selectivity, and dynamic behavior have been assessed. Overall, the BCT-type zeolite clearly stands out for highly selective separations of both D and T over H, achieving the highest reported selectivities at cryogenic temperatures. We also identified other interesting zeolites for the separation of hydrogen isotopes that offer an alternative way to tackle similar isotopic separations by an aimed selection or design of porous materials., This work was supported by the European Research Council through an ERC Starting Grant (ERC2011-StG-279520-RASPA). We thank C3UPO for the HPC support.

Three different hybrid carbon xerogels containing Graphene Oxide (AXGO), Micronized Graphite (AXMG) and Carbon Black (AXCB) were synthesized using an easy, fast and affordable method. These three additives were initially selected to improve the electrical conductivity of the pristine activated carbon xerogel (AX) thus expecting to improve its performance in aqueous supercapacitors. Capacitances of the corresponding devices were measured as a function of current density and results of the high and low charge transfer regime of the supercapacitors were discussed separately. In both regimes, the differences observed between the hybrid electrodes were analyzed on the basis of the concurrent influence of the micro and mesoporosity, surface chemistry and electrical conductivity of the materials. Accordingly, even though all the hybrid carbon xerogels showed higher electrical conductivities, only AXGO rendered a better performance than AX, showing the highest capacitances in the whole interval of intensities studied. Consequently, at 16 A g−1, the energy and power densities of the AXGO supercapacitors increased up to 16% and 97%, respectively, with respect to AX, and of 143% and 409%, respectively, with respect to a commercial activated carbon used as reference. The performance of AXCB and, especially AXMG was worse than AX supercapacitors due to a combination of inadequate pore size distributions and/or a poor surface chemistry. Finally, TEM analysis helped to understand the different way the three additives were affecting the nanostructure (and final properties) of the hybrid carbon xerogels., Authors gratefully acknowledge the financial support from the Ministerio de Economía, Industria y Competitividad from Spain (Project CTQ2017-87820-R). MCR also acknowledges CSIC (Project I.E. 201880E010).

This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.nature.com/articles/s41598-018-23928-9 Diatoms are photosynthetic microalgae, a group with a major environmental role on the planet due to the biogeochemical cycling of silica and global fixation of carbon. However, they can evolve into harmful blooms through a resourceful communication mechanism, not yet fully understood. Here, we demonstrate that a population of diatoms under darkness show quasi-periodic electrical oscillations, or intercellular waves. The origin is paracrine signaling, which is a feedback, or survival, mechanism that counteracts changes in the physicochemical environment. The intracellular messenger is related to Ca2+ions since spatiotemporal changes in their concentration match the characteristics of the intercellular waves. Our conclusion is supported by using a Ca2+channel inhibitor. The transport of Ca2+ions through the membrane to the extracellular medium is blocked and the intercellular waves disappear. The translation of microalgae cooperative signaling paves the way for early detection and prevention of harmful blooms and an extensive range of stress-induced alterations in the aquatic ecosystem. Fundação para a Ciência e Tecnologia grants: (SFRH/BPD/91518/2012, UID/Multi/04326/2013); project SNMB - INOV; Operational Program (OP) Mar 2020; Portugal 2020; European Union: [European Structural Funds and Investment Funds (FEEI) and European Maritime and Fisheries Fund (EMFF)]. info:eu-repo/semantics/publishedVersion

Quality and compositional changes were determined in noni fruit harvested at five ripening stages, from dark-green to thaslucent-grayish. Fruit ripening was accompanied by acidity and soluble solids accumulation but pH diminution, whereas the softening profile presented three differential steps named early (no significant softening), intermediate (significant softening), and final (dramatic softening). At early step the extensive depolymerization of hydrosoluble pectins and the significantly increment of pectinase activities did not correlate with the slight reduction in firmness. The intermediate step showed an increment of pectinases and hemicellulases activities. The final step was accompanied by the most significant reduction in the yield of alcohol-insoluble solids as well as in the composition of uronic acids and neutral sugars; pectinases increased their activity and depolymerization of hemicellulosic fractions occurred. Noni ripening is a process conducted by the coordinated action of pectinases and hemicellulases that promote the differential dissasembly of cell wall polymers.

SUMMARYThe kinetochore is a dynamic multi-protein assembly that forms on each sister chromatid and interacts with microtubules of the mitotic spindle to drive chromosome segregation. In animals, kinetochores without attached microtubules expand their outermost layer into crescent and ring shapes to promote microtubule capture and spindle assembly checkpoint (SAC) signalling. Kinetochore expansion is an example of protein co-polymerization, but the mechanism is not understood. Here, we present evidence that kinetochore expansion is driven by oligomerization of the Rod-Zw10-Zwilch (RZZ) complex, an outer kinetochore component that recruits the motor dynein and the SAC proteins Mad1-Mad2. Depletion of ROD in human cells suppresses kinetochore expansion, as does depletion of Spindly, the adaptor that connects RZZ to dynein, while dynein itself is dispensable. Expansion is also suppressed by mutating ZWILCH residues implicated in Spindly binding. Conversely, supplying cells with excess ROD facilitates kinetochore expansion under otherwise prohibitive conditions. Using the C. elegans early embryo, we demonstrate that ROD-1 has a concentration-dependent propensity for oligomerizing into µm-scale filaments, and we identify the ROD-1 β-propeller as a key regulator of self-assembly. Finally, we show that a minimal ROD-1-Zw10 complex efficiently oligomerizes into filaments in vitro. Our results suggest that RZZ’s capacity for oligomerization is harnessed by kinetochores to assemble the expanded outermost domain, in which RZZ filaments serve as recruitment platforms for SAC components and microtubule-binding proteins. Thus, we propose that RZZ self-assembly into filaments underlies the adaptive change in kinetochore size that contributes to chromosome segregation fidelity.

The spherical agglomeration technique (SAT) has emerged as an innovative alternative for the removal of heavy metals from water at optimum levels of surfactant addition. This technique has achieved high removal efficiencies. In the present study, Yucca decipiens extracts were applied as the biosurfactant for the removal of heavy metals from groundwater of a mining community using SAT. Aqueous models were generated to explain the removal of copper and lead in solutions. It was possible to remove 99.96% and 99.62% respectively. The highest concentrations of copper and lead 209.5 and 2 mg L−1, respectively, were observed at a waterhole in the mining community. This sample was used to test the efficiency of SAT, using optimal conditions of the models. It was possible to remove 99.22% of copper and 91.50% of lead present in the groundwater. High concentrations of sodium and calcium were found. To reduce the residual sodium concentration, the pH was decreased from 11 to 9.5. 99.84% of copper and only 93.49% of lead were removed; the remaining concentrations did not exceed the limit of Mexican regulations (NOM-001-SEMARNAT-1996, 1996). It was demonstrated that the Yucca extracts are effective or the treatment of water with high concentrations of heavy metals under the conditions of SAT.

Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD+levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD+, silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD+levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD+depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-β1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy.

A novel set-up has been designed and used for synchrotron radiation X-ray high-resolution powder diffraction (SR-HRPD) in transmission geometry (spinning capillary) for in situ solid–gas reactions and processes in an isobaric and isothermal environment. The pressure and temperature of the sample are controlled from 10−3 to 1000 mbar and from 80 to 1000 K, respectively. To test the capacities of this novel experimental set-up, structure deformation in the porous material zeolitic imidazole framework (ZIF-8) by gas adsorption at cryogenic temperature has been studied under isothermal and isobaric conditions. Direct structure deformations by the adsorption of Ar and N2 gases have been observed in situ, demonstrating that this set-up is perfectly suitable for direct structural analysis under in operando conditions. The presented results prove the feasibility of this novel experimental station for the characterization in real time of solid–gas reactions and other solid–gas processes by SR-HRPD., The authors are grateful to the SpLine staff for their assistance. Financial support under grant PIE 201060E013 of the Consejo Superior de Investigaciones Científicas-CSIC and the Spanish Ministry of Economy and Competitiveness MINECO is also acknowledged.