Molecular dynamics simulations of elementary chemical processes in liquid water using combined density functional and molecular mechanics potentials. I. Proton transfer in strongly H-bonded complexes

The first molecular dynamics (MD) simulation of a chemical process in solution with an ab initio description of the reactant species and a classical representation of the solvent is presented. We study the dynamics of proton (deuterium) transfer in strongly hydrogen-bonded systems characterized by an energy surface presenting a double well separated by a low activation barrier. We have chosen the hydroxyl-water complex in liquid water to analyze the coupling between the reactive system and the environment. The proton is transferred from one well to the other with a frequency close to 1 ps−1 which is comparable to the low-frequency band associated to hindered translations, diffusional translation and reorientation of water molecules in water. The proton transfer takes place in 20–30 fs whereas the solvent response is delayed by about 50 fs. Therefore, the reaction occurs in an essentially frozen-solvent configuration. In principle, this would produce a barrier increase with respect to the equilibrium reaction path. However, solvent fluctuations play a substantial role by catalyzing the proton transfer. The solvent relaxation time after proton transfer has been evaluated. Since it falls in the same time scale than the reactive events (0.6 ps) it substantially influences the proton dynamics. The present study is intended to model charge transfer processes in polar media having a low activation barrier for which many reactive events may be predicted in a MD simulation. The case of reactions with large activation barriers would require the use of special techniques to simulate rare events. But still in that case, hybrid QM/MM simulations represent a suitable tool to analyze reaction dynamics and non-equilibrium solvent effects in solution [email protected]

Inhibition of the SphK1/S1P signaling pathway by melatonin in mice with liver fibrosis and human hepatic stellate cells

30 p.The sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) system is involved in different pathological processes, including fibrogenesis. Melatonin abrogates activation of hepatic stellate cells (HSCs) and attenuates different profibrogenic pathways in animal models of fibrosis, but it is unknown if protection associates with its inhibitory effect on the SphK1/S1P axis. Mice in treatment groups received carbon tetrachloride (CCl4) 5 μL/g body wt i.p. twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg/kg/day i.p, beginning two weeks after the start of CCl4 administration. At both 4 and 6 weeks following CCl4 treatment, liver mRNA levels, protein concentration and immunohistochemical labelling for SphK1 increased significantly. S1P production, and expression of S1P receptor (S1PR)1, S1PR3 and acid sphingomyelinase (ASMase) were significantly elevated. However, there was a decreased expression of S1PR2 and S1P lyase (S1PL). Melatonin attenuated liver fibrosis, as shown by a significant inhibition of the expression of α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β and collagen (Col) Ι. Furthermore, melatonin inhibited S1P production, lowered expression of SphK1, S1PR1, SP1R3 and ASMase, and increased expression of S1PL. Melatonin induced a reversal of activated human HSCs cell line LX2, as evidenced by a reduction in α-SMA, TGF-β, and Col I expression. Melatonin-treated cells also exhibited an inhibition of the SphK1/S1P axis. Antifibrogenic effect of SphK1 inhibition was confirmed by treatment of LX2 cells with PF543. Abrogation of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in liver fibrogenesi

Melatonin inhibits the sphingosine kinase 1/sphingosine-1-phosphate signaling pathway in rabbits with fulminant hepatitis of viral origin

25 p.The sphingosine kinase (SphK)1/sphingosine-1-phosphate (S1P) pathway is involved in multiple biological processes, including liver diseases. This study investigate whether modulation of the SphK1/S1P system associates to the beneficial effects of melatonin in an animal model of acute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits were experimentally infected with 2x104 hemagglutination units of a RHDV isolate and received 20 mg/kg of melatonin at 0 hr, 12 hr and 24 hr postinfection. Liver mRNA levels, protein concentration and immunohistochemical labelling for SphK1 increased in RHDV-infected rabbits. S1P production and protein expression of the S1PR1 receptor were significantly elevated following RHDV infection. These effects were significantly reduced by melatonin. Rabbits also exhibited increased expression of toll-like receptor (TLR)4, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, nuclear factor-kappa B (NF-κB) p50 and p65 subunits and phosphorylated inhibitor of kappa B (IκB)α. Melatonin administration significantly inhibited those changes and induced a decreased immunoreactivity for RHDV viral VP60 antigen in the liver. Results obtained indicate that the SphK1/S1P system activates in parallel to viral replication and the inflammatory process induced by the virus. Inhibition of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in this animal model of ALF, and supports the potential of melatonin as an antiviral agen

Engineering alginate hydrogel films with poly (3-hydroxybutyrate-co-3-valerate) and graphene nanoplatelets: Enhancement of antiviral activity, cell adhesion and electroactive properties

[EN] A new biodegradable semi-interpenetrated polymer network (semi-IPN) of two US Food and Drug Administration approved materials, poly(3-hydroxybutyrate-co-3-valerate) (PHBV) and calcium alginate (CA) was engineered to provide an alternative strategy to enhance the poor adhesion properties of CA. The synthesis procedure allows the additional incorporation of 10 % w/w of graphene nanoplatelets (GNPs), which have no cytotoxic effect on human keratinocytes. This quantity of multilayer graphene provides superior antiviral activity to the novel semi-IPN against a surrogate virus of SARS-CoV-2. Adding GNPs hardly affects the water absorption or electrical conductivity of the pure components of CA and PHBV. However, the semi-IPN's electrical conductivity increases dramatically after adding GNP due to molecular rearrangements of the intertwined polymer chains that continuously distribute the GNP nanosheets, This new hydrophilic composite biomaterial film shows great promise for skin biomedical applications, especially those that require antiviral and/or biodegradable electro-conductive materials.This research was funded by the Fundacion Universidad Catolica de Valencia San Vicente Martir, Grant 2020-231-006UCV, the Spanish Ministry of Science and Innovation (PID2020-119333RB-I00/AEI/10.13039/501100011033) (awarded to ?A.S-A) , and the FEDER/Spanish Ministry of Science and Innovation-Agencia Estatal de Investigacion through the Project RTI2018-097862-B-C21 (awarded to R.S.i.S) . CIBER-BBN is an initiative funded by the VI National R & D & I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Ac-tions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Hurtado, A.; Cano-Vicent, A.; Tuñón-Molina, A.; Aparicio-Collado, JL.; Sabater I Serra, R.; Salesa, B.; Serrano-Aroca, Á. (2022). Engineering alginate hydrogel films with poly (3-hydroxybutyrate-co-3-valerate) and graphene nanoplatelets: Enhancement of antiviral activity, cell adhesion and electroactive properties. International Journal of Biological Macromolecules. 219:694-708. https://doi.org/10.1016/j.ijbiomac.2022.08.03969470821

Search for Blue Compact Dwarf Galaxies During Quiescence

Blue Compact Dwarf (BCD) galaxies are metal poor systems going through a major starburst that cannot last for long. We have identified galaxies which may be BCDs during quiescence (QBCD), i.e., before the characteristic starburst sets in or when it has faded away. These QBCD galaxies are assumed to be like the BCD host galaxies. The SDSS/DR6 database provides ~21500 QBCD candidates. We also select from SDSS/DR6 a complete sample of BCD galaxies to serve as reference. The properties of these two galaxy sets have been computed and compared. The QBCD candidates are thirty times more abundant than the BCDs, with their luminosity functions being very similar except for the scaling factor, and the expected luminosity dimming associated with the end of the starburst. QBCDs are redder than BCDs, and they have larger HII region based oxygen abundance. QBCDs also have lower surface brightness. The BCD candidates turn out to be the QBCD candidates with the largest specific star formation rate (actually, with the largest H_alpha equivalent width). One out of each three dwarf galaxies in the local universe may be a QBCD. The properties of the selected BCDs and QBCDs are consistent with a single sequence in galactic evolution, with the quiescent phase lasting thirty times longer than the starburst phase. The resulting time-averaged star formation rate is low enough to allow this cadence of BCD -- QBCD phases during the Hubble time.Comment: Accepted for publication in ApJ. 17 pages. 13 Fig

Non-Woven Infection Prevention Fabrics Coated with Biobased Cranberry Extracts Inactivate Enveloped Viruses Such as SARS-CoV-2 and Multidrug-Resistant Bacteria

[EN] The Coronavirus Disease (COVID-19) pandemic is demanding the rapid action of the authorities and scientific community in order to find new antimicrobial solutions that could inactivate the pathogen SARS-CoV-2 that causes this disease. Gram-positive bacteria contribute to severe pneumonia associated with COVID-19, and their resistance to antibiotics is exponentially increasing. In this regard, non-woven fabrics are currently used for the fabrication of infection prevention clothing such as face masks, caps, scrubs, shirts, trousers, disposable gowns, overalls, hoods, aprons and shoe covers as protective tools against viral and bacterial infections. However, these non-woven fabrics are made of materials that do not exhibit intrinsic antimicrobial activity. Thus, we have here developed non-woven fabrics with antimicrobial coatings of cranberry extracts capable of inactivating enveloped viruses such as SARS-CoV-2 and the bacteriophage phi 6 (about 99% of viral inactivation in 1 min of viral contact), and two multidrug-resistant bacteria: the methicillin-resistant Staphylococcus aureus and the methicillin-resistant Staphylococcus epidermidis. The morphology, thermal and mechanical properties of the produced filters were characterized by optical and electron microscopy, differential scanning calorimetry, thermogravimetry and dynamic mechanical thermal analysis. The non-toxicity of these advanced technologies was ensured using a Caenorhabditis elegans in vivo model. These results open up a new prevention path using natural and biodegradable compounds for the fabrication of infection prevention clothing in the current COVID-19 pandemic and microbial resistant era.This research was supported by the Fundacion Universidad Catolica de Valencia San VicenteMartir, Grant 2020-231-006UCV and by the Ministerio de Ciencia e Innovacion: project PID2020-119333RB-I00/AEI/10.13039/501100011033 (awarded to A.S.-A.) and project RTI2018-097862-B-C21 (awarded to R.S.i.S. including FEDER funding). CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. This research was also supported by grants from the Japan Agency for Medical Research and Development (AMED) (20fk0108533h0001), and the JST Core Research for Evolutional Science and Technology (JPMJCR20HA). This work was supported by the Joint Usage/Research Center program of Institute for Frontier Life and Medical Sciences Kyoto University.Takayama, K.; Tuñón-Molina, A.; Cano-Vicent, A.; Muramoto, Y.; Noda, T.; Aparicio-Collado, JL.; Sabater I Serra, R.... (2021). Non-Woven Infection Prevention Fabrics Coated with Biobased Cranberry Extracts Inactivate Enveloped Viruses Such as SARS-CoV-2 and Multidrug-Resistant Bacteria. International Journal of Molecular Sciences. 22(23):1-17. https://doi.org/10.3390/ijms222312719117222

Ácidos grasos de lípidos intramusculares y grasa de cobertura en búfalos suplementados con aceite de pescado

El objetivo fue investigar la influencia de la suplementación dietaria de búfalos con aceite de pescado sobre el ácido linoleico conjugado (ALC) y los ácidos grasos Ω6 y Ω3 en lípidos intramusculares (IM) y grasa de cobertura (GC). Se emplearon veinte animales divididos en dos grupos alimentados sobre Brachiaria brizantha y suplementados con 3 kg de afrecho de arroz, 500 g de maíz y 500 g de pellet de girasol, durante 60 días. El grupo I se mantuvo con esta dieta, el II recibió adicionalmente 100 ml/día de aceite de pescado por animal. Los resultados (expresados en mg/g grasa) indicaron una disminución de ácido palmítico en IM y GC del grupo II (189,05) vs grupo I (206,97) y en II (259,72) vs I (280,84) respectivamente. El ALC se incrementó levemente en IM y GC del grupo II (17,09) vs I (11,56) y en el II (16,80) vs I (11,75) respectivamente. El ácido linoleico (18:2 n6) en IM del grupo II (23,45) disminuyó en relación con el I (38,19) y en GC del grupo II (13,21) se incrementó levemente con relación al I (12,71). El ácido alfa linolénico (18:3 n3) en IM de grupos I y II fue similar (8,37 y 8,69), en cambio el contenido de dicho ácido en GC fue menor en el grupo I (4,70) comparado con el grupo II (6,05). La relación Ω6/Ω3 en IM y GC fue más estrecha en el grupo II (2,69:1) y (2,18:1) con relación al grupo I (4,55:1) y (2,70:1) respectivamente. La suplementación con aceite de pescado produjo disminución del ácido linoleico, mejorando la relación entre Ω6/Ω3. Además causó una leve disminución de los valores de ácido palmítico y un pequeño aumento de ALC

Molecular dynamics simulations of elementary chemical processes in liquid water using combined density functional and molecular mechanics potentials. II. Charge separation processes

A new approach to carry out molecular dynamics simulations of chemical reactions in solution using combined density functional theory/molecular mechanics potentials is presented. We focus our attention on the analysis of reactive trajectories, dynamic solvent effects and transmission coefficient rather than on the evaluation of free energy which is another important topic that will be examined elsewhere. In a previous paper we have described the generalities of this hybrid molecular dynamics method and it has been employed to investigate low energy barrier proton transfer process in water. The study of processes with activation energies larger than a few kT requires the use of specific techniques adapted to “rare events” simulations. We describe here a method that consists in the simulation of short trajectories starting from an equilibrated transition state in solution, the structure of which has been approximately established. This calculation is particularly efficient when carried out with parallel computers since the study of a reactive process is decomposed in a set of short time trajectories that are completely independent. The procedure is close to that used by other authors in the context of classical molecular dynamics but present the advantage of describing the chemical system with rigorous quantum mechanical calculations. It is illustrated through the study of the first reaction step in electrophilic bromination of ethylene in water. This elementary process is representative of many charge separation reactions for which static and dynamic solvent effects play a fundamental [email protected]

3D‐Printed Porous Organic Cages for Gas Filtration: Fabrication and Flow Simulations

AbstractPorous organic cages (POCs) are a class of emerging porous materials with high porosity and selectivity for gas adsorption and separation. As a representative of first‐generation POCs, the cage molecule CC3, has huge potential for separating noble gases and volatile organic compounds (VOCs). 3D printing CC3 using direct ink writing (DIW) offers significant advantages to build complex structures. Through rational design, formulations that are both printable and functional are achieved. Optimised formulations have the elasto‐visco‐plastic behavior required while retaining the functional properties of the cages. The characterization of printed parts evidence that the CC3 structure and adsorption capacity are well preserved. BET surface areas vary with CC3 concentration and can reach up to ≈249 m2 g−1 for 70 wt% CC3. However, high CC3 content leads to a decrease in shrinkage, higher porosity, and low compressive strength ≈0.7 MPa. Computational fluid dynamics (CFD) is used to investigate the gas flow behavior through grid‐type structures with tailored geometric parameters. The results reveal that changing the offset distance and porosity manipulates the flow path, velocity distribution, and pressure drop. This work provides a pathway to design and fabricate structures with multi‐scale porosity that can be widely used for other functional materials and applications.</jats:p

Biocompatible Alginate Film Crosslinked with Ca2+ and Zn2+ Possesses Antibacterial, Antiviral, and Anticancer Activities

Alginate is a highly promising biopolymer due to its non-toxic and biodegradable properties. Alginate hydrogels are often fabricated by cross-linking sodium alginate with calcium cations and can be engineered with highly desirable enhanced physical and biological properties for biomedical applications. This study reports on the anticancer, antiviral, antibacterial, in vitro, and in vivo toxicity, water absorption, and compound release properties of an alginate hydrogel crosslinked with calcium and different amounts of zinc cations. The results showed that the calcium alginate hydrogel film crosslinked with the highest amount of zinc showed similar water sorption properties to those of calcium alginate and released a suitable amount of zinc to provide anticancer activity against melanoma and colon cancer cells and has antibacterial properties against methicillin-resistant and antiviral activity against enveloped and non-enveloped viruses. This film is non-toxic in both in vitro in keratinocyte HaCaT cells and in vivo in the model, which renders it especially promising for biomedical applications