Coronary heart disease (CHD) is preventable, but the methods for assessing risk and monitoring response rely on imprecise lipid-based assessments. Recently, we have shown that an integrated genetic−epigenetic test that includes three methylation-sensitive digital PCR assays predicts 3-year risk for incident CHD better than lipid-based methods. However, whether methylation sites change in response to therapies that alter CHD risk is not known. Therefore, we assessed methylation at these three incident CHD-related sites in DNA from 39 subjects before and after three months of biochemically verified smoking cessation, then analyzed the relationship between change in methylation at each of the sites to the change in smoking intensity as assessed by cg05575921 methylation. We found that, in those who quit smoking, methylation change at one CHD risk marker (cg00300879) was significantly associated with change in cg05575921 methylation (p < 0.04). We conclude that changes in incident CHD-r... [more]

The authors wish to remove every commercial reference reported in the discussion of the published paper in Processes [...]

The prediction of epileptic seizures is crucial to aid patients in gaining early warning and taking effective intervention. Several features have been explored to predict the onset via electroencephalography signals, which are typically non-stationary, dynamic, and varying from person-to-person. In the former literature, features applied in the classification have shared similar contributions to all patients. Therefore, in this paper, we analyze the impact of the specific combination of feature and channel from time, frequency, and time−frequency domains on prediction performance of disparate patients. Based on the minimal-redundancy-maximal-relevance criterion, the proposed framework uses a sequential forward selection approach to individually find the optimal features and channels. Trained models could discriminate the pre-ictal and inter-ictal electroencephalography with a sensitivity of 90.2% and a false prediction rate of 0.096/h. We also present the comparison between the classif... [more]

Microbial fuel cells (MFCs) have emerged as a sustainable technology for wastewater treatment that has potential to recycle bioelectricity from livestock wastewater. The performance of MFCs is influenced by the synergistic effect of anode material with nearby microorganisms. In this study, three identical double-chambered MFCs with different anode carbon clothes using swine wastewater are established. The optimization mechanism of MFC performance is analyzed by anode characteristics, cell performance, and microbial community, respectively. The results show that the surface structure and properties of the anode carbon cloth can be obviously improved by the acid−heat-modified treatment. The community structure of anodic biofilm, which varied with different modification methods, was mainly dominated by Proteobacteria, Firmicutes, and Bacteroidetes. These findings demonstrate efficient and simple methods for improving the performance of MFCs based on swine wastewater and may help to explor... [more]

Drug repositioning is a strategy to identify new uses for existing, approved, or research drugs that are outside the scope of its original medical indication. Drug repurposing is based on the fact that one drug can act on multiple targets or that two diseases can have molecular similarities, among others. Currently, thanks to the rapid advancement of high-performance technologies, a massive amount of biological and biomedical data is being generated. This allows the use of computational methods and models based on biological networks to develop new possibilities for drug repurposing. Therefore, here, we provide an in-depth review of the main applications of drug repositioning that have been carried out using biological network models. The goal of this review is to show the usefulness of these computational methods to predict associations and to find candidate drugs for repositioning in new indications of certain diseases.

Titan’s haze is strongly suspected to be an HCN-derived polymer, but despite the first in situ measurements by the ESA-Huygens space probe, its chemical composition and formation process remain largely unknown. To investigate this question, we simulated the atmospheric haze formation process, experimentally. We synthesized analogues of Titan’s haze, named Titan tholins, in an irradiated N2−CH4 gas mixture, mimicking Titan’s upper atmosphere chemistry. HCN was monitored in situ in the gas phase simultaneously with the formation and evolution of the haze particles. We show that HCN is produced as long as the particles are absent, and is then progressively consumed when the particles appear and grow. This work highlights HCN as an effective precursor of Titan’s haze and confirms the HCN-derived polymer nature of the haze.

We aimed to assess the prescription trends of combined antiretroviral therapy (cART) in one infectious diseases department and the cost-efficacy (C/E) of different regimens used in treatment-naïve patients. The C/E was assessed with a software application developed by a group of researchers in Spain. The efficacy was already calculated in the application. The costs included the local cost of antiretrovirals and other direct costs specific to our institution. In the software application, the C/E reference regimen was ABC/3TC/DTG. In total, 181 HIV-infected patients were diagnosed and initiated cART during 2015−2019. The proportion of patients treated with integrase-strand transfer inhibitor (INSTI)-based regimens increased from 2015−2018 (54%) to the end of 2019 (81%). The relative C/E ranged from 0.90 to 1.28 for the evaluated INSTI-based regimens. Among INSTI-based regimens, ABC/3TC/DTG and TAF/FTC/EVG/c are the regimens with similar efficacy and relative C/E.

Sialyllactose (SL) is one of the most important acidic oligosaccharides in human milk, which plays an important role in the health of infants. In this work, an efficient multi-enzyme cascade was developed in a single whole cell to produce 3′-SL. We constructed two compatible plasmids with double cloning sites to co-express four genes. Different combinations were assessed to verify the optimal catalytic ability. Then, the conversion temperature, pH, and stability under the optimal temperature and pH were investigated. Moreover, the optimal conversion conditions and surfactant concentration were determined. By using the optimal conditions (35 °C, pH 7.0, 20 mM polyphosphate, 10 mM cytidine monophosphate (CMP), 20 mM MgCl2), 25 mL and 4 L conversion systems were carried out to produce 3′-SL. Similar results were obtained between different volume conversion reactions, which led the maximum production of 3′-SL to reach 53 mM from 54.2 mM of sialic acid (SA) in the 25 mL system and 52.8 mM o... [more]

Here, we present a novel approach for the transient permeabilization of cells. We combined laminar shear flow in a microchannel with chaotic advection employing surface acoustic waves. First, as a fundamental result on the one hand, and as a kind of reference measurement for the more complex acoustofluidic approach on the other hand, we studied the permeabilization of cells in pure shear flow in a microchannel with Y-geometry. As a proof of principle, we used fluorescent dyes as model drugs and investigated their internalization into HeLa cells. We found that drug uptake scaled non-linearly with flow rate and thus shear stress. For calcein, we obtained a maximal enhancement factor of about 12 at an optimum flow rate of Q = 500 µL/h in the geometry used here compared to static incubation. This result is discussed in the light of structural phase transitions of lipid membranes accompanied by non-linear effects, as the plasma membrane is the main barrier to overcome. Second, we demonstrat... [more]

This study aims to evaluate the potential of consortium biomass formation between Mucor circinelloides, an oleaginous filamentous fungal species, and Chlorella vulgaris, in order to promote a straightforward approach to harvest microalgal cells and to evaluate the lipid production in the consortium system. A synthetic medium with glucose (2 g·L−1) and mineral nutrients essential for both fungi and algae was selected. Four different inoculation strategies were assessed, considering the effect of simultaneous vs. separate development of fungal spores and algae cells, and the presence of a supporting matrix aiming at the higher recovery of algae cell rates. The results were evaluated in terms of consortium biomass composition, demonstrating that the strategy using a mature fungal mycelium with a higher algae count may provide biomass samples with up to 79% of their dry weight as algae, still promoting recovery rates greater than 97%. The findings demonstrate a synergistic effect on the li... [more]

Biomass pretreatment is a mandatory step for the biochemical conversion of lignocellulose to chemicals. During pretreatment, soluble compounds are released into the prehydrolyzate that inhibit the enzymatic hydrolysis step. In this work, we investigated how the reaction conditions in steam explosion pretreatment of beechwood (severity: 3.0−5.25; temperature: 160−230 °C) influence the resulting amounts of different inhibitors. Furthermore, we quantified the extent of enzyme inhibition during enzymatic hydrolysis of Avicel in the presence of the prehydrolyzates. The amounts of phenolics, HMF, acetic acid and formic acid increased with increasing pretreatment severities and maximal quantities of 21.6, 8.3, 43.7 and 10.9 mg/gbeechwood, respectively, were measured at the highest severity. In contrast, the furfural concentration peaked at a temperature of 200 °C and a severity of 4.75. The presence of the prehydrolyzates in enzymatic hydrolysis of Avicel lowered the glucose yields by 5−26%.... [more]

Aimed at the low ratio of carbon and nitrogen (C/N, approximately 7/1) of waste activated sludge (WAS), which would inhibit the acetogenesis process during anaerobic fermentation, this study introduced three brewing wastes, including vinegar (VR), stillage (SR) and soy sauce (SSR) residues, to promote acetogenesis by co-fermenting with WAS. Results showed that different brewing wastes contributed differently to the volatile fatty acids (VFAs) yield. The best performance was observed with SSR (4517 ± 367 mg COD/L), particularly rich in C2−C3 VFAs, corresponding to 40% and 52% higher concentrations than with SR and VR, respectively. Meanwhile, the hydrolysis rate constant peaked at 0.0059 h−1 in the SSR test, compared to the sole WAS test (0.0018 h−1). Furthermore, canonical correlation analysis reflected that the functional consortia, known to ferment saccharides/amino acids into C2−C3 VFAs (i.e., Proteiniclasticum, Petrimonas, Cloacibacillus and Gemmobacter), was related to the charact... [more]

Gefitinib (Gef) is a poorly water-soluble antitumor drug, which shows poor absorption/bioavailability after oral administration. Therefore, this study was carried out to develop Gef solid dispersions (SDs) using different carriers and different techniques in order to enhance its dissolution and oral absorption/bioavailability. Various SD formulations of Gef were established using fusion and microwave methods utilizing Soluplus, Kollidone VA64, and polyethylene glycol 4000 (PEG 4000) as the carriers. Developed SDs of Gef were characterized physicochemically and evaluated for in vitro dissolution and in vivo pharmacokinetic studies. The physicochemical evaluation revealed the formation of Gef SDs using fusion and microwave methods. In vitro dissolution studies indicated significant release of Gef from all SDs compared to the pure Gef. Optimized SD of Gef (S2-MW) presented significant release of Gef (82.10%) compared with pure Gef (21.23%). The optimized Gef SD (S2) was subjected to in vi... [more]

The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (neuropathy, ataxia and retinitis pigmentosa). The equivalent point mutation introduced in yeast Saccharomyces cerevisiae mitochondrial DNA considerably reduced the activity of ATP synthase and of cytochrome-c-oxidase, preventing yeast growth on oxidative substrates. The overexpression of the mitochondrial oxodicarboxylate carrier (Odc1p) was able to rescue the growth on the oxidative substrate by increasing the substrate-level phosphorylation of ADP coupled to the conversion of α-ketoglutarate (AKG) into succinate with an increase in Complex IV activity. Previous studies showed that equivalent point mutations in ATP synthase behave similarly and can be rescued by Odc1p overexpression and/or the uncoupling of OXPHOS from ATP synthesis. In order to better understand the mechanism of the ATP synthase mutation bypass, we developed a core model of mitochondrial metabolism based on AKG as a respiratory... [more]

Pyrolysis is an important technology to convert lignocellulosic biomass to a renewable liquid energy carrier known as pyrolysis oil or bio-oil. Herein we report the pyrolysis of pigeon pea wood, a widely available biomass in the Philippines, in a semi-continuous reactor at gram scale. The effects of process conditions such as temperature (400−600 °C), nitrogen flow rate (7−15 mL min−1) and particle size of the biomass feed (0.5−1.3 mm) on the product yields were determined. A Box-Behnken three-level, three-factor fractional factorial design was carried out to establish process-product yield relations. Of particular interest is the liquid product (bio-oil), of which the yield was shown to depend on all independent variables in a complex manner. The optimal conditions for highest bio-oil yield (54 wt.% on dry feed intake) were a temperature of 466 °C, a nitrogen flow rate of 14 mL min−1 and a particle size of 1.3 mm. Validation of the optimized conditions proved that the average (n = 3)... [more]

Hydrothermal liquefaction (HTL) is a promising thermochemical process to treat wet feedstocks and convert them to chemicals and fuels. In this study, the effects of final temperature (300, 325, and 350 °C), reaction time (30 and 60 min), rice-straw-to-water ratio (1:1, 1:5, 1:10, and 1:15 (wt./wt.)), methanol-to-water ratio (0:100, 25:75, 50:50, and 75:25 (vol.%/vol.%)), and alkali catalysts (KOH, NaOH, and K2CO3) on product yields, composition of bio-crude, higher heating value (HHV) of bio-crude and bio-char, and energy recovery on HTL of rice straw are investigated. At the optimal processing condition corresponding to the final temperature of 300 °C, 60 min reaction time, and rice-straw-to-water ratio of 1:10 at a final pressure of 18 MPa, the bio-crude yield was 12.3 wt.% with low oxygen content (14.2 wt.%), high HHV (35.3 MJ/kg), and good energy recovery (36%). The addition of methanol as co-solvent to water at 50:50 vol.%/vol.% improved the yield of bio-crude up to 36.8 wt.%. The... [more]

Microbial electrosynthesis (MES) systems can convert CO2 to acetate and other value-added chemicals using electricity as the reducing power. Several electrochemically active redox mediators can enhance interfacial electron transport between bacteria and the electrode in MES systems. In this study, different redox mediators, such as neutral red (NR), 2-hydroxy-1,4-naphthoquinone (HNQ), and hydroquinone (HQ), were compared to facilitate an MES-based CO2 reduction reaction on the cathode. The mediators, NR and HNQ, improved acetate production from CO2 (165 mM and 161 mM, respectively) compared to the control (without a mediator = 149 mM), whereas HQ showed lower acetate production (115 mM). On the other hand, when mediators were used, the electron and carbon recovery efficiency decreased because of the presence of bioelectrochemical reduction pathways other than acetate production. Cyclic voltammetry of an MES with such mediators revealed CO2 reduction to acetate on the cathode surface. T... [more]

This study investigated the cytotoxicity, anti-obesity and anti-diabetic potentials of blanched, aqueous and ethanol extracts of Heteromorpha arborescens (Spreng.) Cham leaves. The results revealed that both ethanol and aqueous extracts exhibited considerable inhibition against α-glucosidase (IC50 of 627.29 ± 4.62 µg/mL and 576.46 ± 3.21 µg/mL respectively), while the blanched extract showed weak α-glucosidase inhibition (IC50; 855.38 ± 4.29 µg/mL) and the aqueous extract showed the best α-amylase inhibition (IC50; 583.74 ± 5.87 µg/mL). However, weak α-amylase inhibition was observed in the ethanol (IC50; 724.60 ± 4.33 µg/mL) and blanched extracts (IC50; 791.63 ± 3.76 µg/mL). The toxicity of the extracts is indicated by LC50 values as 154.75 µg/mL, 125 µg/mL and 90.58 µg/mL for ethanol, aqueous and blanched extracts respectively, indicating the blanched extract to be the most toxic. Moderate glucose utilization in both C3A and L6 cells was also observed for the aqueous and ethanol extr... [more]

Fission yeast is commonly used as a model organism in eukaryotic cell growth studies. To describe the cells’ length growth patterns during the mitotic cycle, different models have been proposed previously as linear, exponential, bilinear and biexponential ones. The task of discriminating among these patterns is still challenging. Here, we have analyzed 298 individual cells altogether, namely from three different steady-state cultures (wild-type, wee1-50 mutant and pom1Δ mutant). We have concluded that in 190 cases (63.8%) the bilinear model was more adequate than either the linear or the exponential ones. These 190 cells were further examined by separately analyzing the linear segments of the best fitted bilinear models. Linear and exponential functions have been fitted to these growth segments to determine whether the previously fitted bilinear functions were really correct. The majority of these growth segments were found to be linear; nonetheless, a significant number of exponential... [more]

In this article, the effects of microwave frequency (2450 MHz and 5800 MHz) and gas humidity (1%, 2%, 3%, 4%, 6% and 8%) on in vitro blood coagulation with cold atmospheric pressure plasma (CAPP) were investigated. The generation of reactive oxygen species (ROS, OH, O) was measured by optical emission spectra. The exposure temperature on blood droplets under treatment was below 55 °C in all cases, to avoid the thermal effect of plasma on the blood clotting. Investigations showed that, with the increase of frequency, the doses of ROS increased, the blood sample presented a more serious collapse and its surface became drier. The humidity of ionized gas can also accelerate the generation of ROS and the process of blood clotting. Our results propose a method to accelerate in vitro blood coagulation in CAPP by adjusting microwave frequency and gas humidity, and suggest a clinical benefit for plasma treatment as a coagulation device in surgery.

Ozone is an allotropic form of oxygen, so in the medical field ozone therapy has special effects. Starting from the premise that bio-oxidative ozone therapy reduces the number of bacteria, in the present study two approaches were proposed: to evaluate the biological effects of ozone gas on the tooth enamel remineralization process and to demonstrate its impact on the morphology and confluence of human primary gingival cells, namely keratinocytes (PGK) and fibroblasts (HGF). The ozone produced by HealOzone was applied in vivo to 68 M1s (first permanent molars), both maxillary and mandibular, on the occlusal surfaces at pit and fissure. The molars included in the study recorded values between 13 and 24 according to the DIAGNOdent Pen 2190 scale, this being the main inclusion/exclusion criterion for the investigated molars. Because the gas can make contact with primary gingival cells during the ozonation process, both human gingival fibroblasts and keratinocytes were exposed to different... [more]

The accessibility of cheap fossil fuels, due to large government subsidies, promotes the accelerated gross domestic product (GDP) per capita growth in Southeast Asia. However, the ambient air pollution from fossil fuel combustion has a latent cost, which is the public health issues such as respiratory diseases, lung cancer, labor loss, and economic burden in the long-run. In Southeast Asia, lung cancer is the leading and second leading cause of cancer-related death in men, and women, respectively. This nexus study employs the panel vector error correction model (VECM) and panel generalized method of moments (GMM) using data from ten Southeast Asian countries from the period (2000−2016) to explore the possible association between emissions, lung cancer, and the economy. The results confirm that CO2 and PM2.5 are major risk factors for lung cancer in the region. Additionally, the increasing use of renewable energy and higher healthcare expenditure per capita tend to reduce the lung cance... [more]

This study assessed the feasibility of using bleached cellulose pulp from Eucalyptus wood as a feedstock for the production of itaconic acid by fermentation. Additionally, different process strategies were tested with the aim of selecting suitable conditions for an efficient production of itaconic acid by the fungus Aspergillus terreus. The feasibility of using cellulose pulp was demonstrated through assays that revealed the preference of the strain in using glucose as carbon source instead of xylose, mannose, sucrose or glycerol. Additionally, the cellulose pulp was easily digested by enzymes without requiring a previous step of pretreatment, producing a glucose-rich hydrolysate with a very low level of inhibitor compounds, suitable for use as a fermentation medium. Fermentation assays revealed that the technique used for sterilization of the hydrolysate (membrane filtration or autoclaving) had an important effect in its composition, especially on the nitrogen content, consequently af... [more]

Microbial lipids have been considered as promising resources for the production of renewable biofuels and oleochemicals. Various feedstocks, including sugars, crude glycerol, and volatile fatty acids, have been used as substrates for microbial lipid production, yet amino acid (AA) wastes remain to be evaluated. Here, we describe the potential to use AA wastes for lipid production with a two-stage culture mode by an oleaginous yeast strain Rhodosporidium toruloides CGMCC 2.1389. Each of the 20 proteinogenic AAs was evaluated individually as sole carbon source, with 8 showing capability to facilitate cellular lipid contents of more than 20%. It was found that L-proline was the most favored AA, with which cells accumulated lipids to a cellular lipid content of 37.3%. When blends with AA profiles corresponding to those of meat industry by-products and sheep viscera were used, the cellular lipid contents reached 27.0% and 28.7%, respectively. The fatty acid compositional analysis of these l... [more]

The Caribbean has been experiencing beach inundations of pelagic Sargassum, causing environmental, health and financial issues. This study showed variations in the composition and methane potential (MP) between the species of Sargassum. The MPs for S. natans VIII, S. natans I and S. fluitans (145, 66 and 113 mL CH4 g−1 Volatile Solids) were considerably below theoretical potentials, possibly due to the high levels of indigestible fibre and inhibitors. The mixed mats Sargassum composition was substantially different from the individual species, being higher in ash, calcium, iron, arsenic and phenolics. The mixed mats produced no methane, perhaps due to the high levels of phenolics. There was a strong correlation between MP and phenolic content. Heavy metals and metalloids were at levels that should not cause concern, except for arsenic (21−124 mg kg−1 dry weight). Further work on the speciation of arsenic in Sargassum is required to fully determine the risk to health and agriculture. Bo... [more]