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1.
Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.  相似文献   
2.
Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.  相似文献   
3.
We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case–control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18–31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m2, p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m2, p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m2, p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m2, p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m2, p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m2, p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = −0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms.  相似文献   
4.
Research on biopolymers-based active films produced with natural antioxidants and/or antimicrobials has gained attention over the last few years; however, anti-mold activity has been less studied than those of anti-bacteria. The aim of this work was the development and characterization of bi-layer films based on gelatin with natamycin and/or “Pitanga” leaf hydroethanolic extract in the second thin layer in order to determine the effects of these bioactive compounds on bi-layered film properties. The films were characterized regarding their moisture content and solubility in water, optical properties, microstructure, mechanical and thermal properties, water contact angle, water vapor permeability, UV/visible light transmission, X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, and antioxidant and anti-mold activities. Active films presented activity against Penicillium spp and Aspergillus niger and demonstrated antioxidant activity, as measured by ABTS •+ and DPPH methods. Neither additive used in the films' second layer significantly affected the films' moisture content, thermal properties or the molecular interactions of the polymer matrix, assessed by FTIR, although some mechanical properties were affected, and the water contact angle. In conclusion, bi-layer films have reduced the quantity of additives required to maintain the antioxidant and anti-mold activities, as compared to similar monolayer films of the same thickness.  相似文献   
5.
6.

Over the last decade, AMD waters have gained more attention as a potential source of metals due to the emerging need to recover or recycle metals from secondary resources. Metals recovery supports sustainability and the development of a circular economy with benefits for resource conservation and the environment. In this study, five extractants (Acorga M5640, LIX 54, LIX 622, LIX 622 N, and LIX 864) diluted (15% (v/v)) in Shell GTL with 2.5% (v/v) octanol were compared and evaluated for Cu recovery from an extreme AMD sample (5.3?±?0.3 g/L Cu) collected at the inactive São Domingos Mine in the Iberian Pyrite Belt of Portugal. Of the five extractants, Acorga M5640 showed the best selective efficiency. Further tests showed that 30% (v/v) of this extractant was able to selectively extract ≈ 96.0% of the Cu from the AMD in one extraction step and all of the remaining Cu (to below detection) in three steps. Among the different stripping agents tested, 2 M sulfuric acid was the most efficient, with ≈ 99% of the Cu stripped, and the recyclability of the organic phase was confirmed in five successive cycles of extraction and stripping. Furthermore, contact time tests revealed that the extraction kinetics allows the transfer of ≈ 97% of the Cu in 15 min, and aqueous to organic phase ratios tests demonstrated a maximum loading capacity of ≈ 16 g/L Cu in the organic phase. Raising the concentration of Cu in the stripping solution (2 M sulfuric acid) to ≈ 46 g/L through successive striping steps showed the potential to recover elemental Cu using traditional electrowinning. Finally, a biological approach for Cu recovery from the stripping solution was evaluated by adding the supernatant of a sulfate-reducing bacteria culture to make different molar ratios of biogenic sulfide to copper; ratios over 1.75 resulted in precipitation of more than 95% of the Cu as covellite nanoparticles.

Graphical Abstract
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7.
The study aims to evaluate the technological properties of autochthonous strains (Lactobacillus sakei S15, Lactobacillus plantarum S24, L. plantarum S91, Pediococcus pentosaceus S128b and Staphylococcus carnosus G109) in Turkish dry fermented sausage (sucuk). After 24 h of fermentaPtion, all lactic acid bacteria strains reduced the pH to below 5.0, while the pH in the control group was above 5.3. The number of lactic acid bacteria strains reached 108–109 cfu g−1 during fermentation. Staphylococcus carnosus G109 remained at the inoculation level of 106 cfu g−1 during ripening. Lactobacillus sakei S15 as mono-culture showed higher TBARS values compared to other strains. The control group had the lowest L* value and autochthonous strains caused no significant difference for a* value. According to principal component analysis results, most volatile compounds were positively correlated with the group containing only L. sakei S15.  相似文献   
8.
9.
International Journal of Information Security - The introduction of advanced metering infrastructure (AMI) smart meters has given rise to fine-grained electricity usage data at different levels of...  相似文献   
10.
Journal of Low Temperature Physics - This study modeled and investigated the magnetocaloric effect in Ni2MnGa Heusler alloy characterized by its magnetic entropy change (ΔSm) and its...  相似文献   
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