The pharmacological properties of melatonin are well known. However, there is noticeable the lack of clinical trials that confirm the efficacy, security, absence of side effects in the short and long ...term, and the effective doses of melatonin. This point is especially important in diseases with high morbidity and mortality including COVID‐19. There is not treatment for COVID‐19, and several anti‐inflammatory and antiviral molecules are being tested, and different vaccines are in preparation. Although the SARS‐CoV‐2 pandemic is apparently improving, it is expected new resurges next fall. Thus, looking for an effective treatment of COVID‐19 is mandatory. Melatonin has significant anti‐inflammatory, antioxidant, and mitochondrial protective effects, and its efficacy has been demonstrated in multiple experimental models of disease and in a clinical trial in sepsis. Because COVID‐19 courses with a severe septic response, multiple reviews proposing melatonin as a treatment for COVID‐19 have been published. Nevertheless, there is a lack of experimental and clinical data on the use of melatonin on SARS‐CoV‐2 infection. Accordingly, we designed a clinical trial with an injectable formulation of melatonin for intravenous perfusion in ICU patients suffering from COVID‐19 that has been just approved by the Spanish Agency of Medicines and Medical Devices (AEMPS). The trial will allow by the first time understand the doses and efficacy of melatonin against COVID‐19.
Cytochrome c (cyt-c) release from the mitochondria to the cytosol is a key process in the initiation of hepatocyte apoptosis involved in the progression of non-alcoholic fatty liver disease (NAFLD) ...to fibrosis, cirrhosis and hepatocellular carcinoma. Hepatocyte apoptosis may be related to lipotoxicity due to the accumulation of palmitic acid and palmitoyl-CoA (Pal-CoA). Therefore, the aim of this study is to examine whether Pal-CoA induces cyt-c release from liver mitochondria of sucrose-fed rat (SF). Pal-CoA-induced cyt-c release was sensitive to cyclosporine A indicating the involvement of the mitochondrial membrane permeability transition (mMPT). In addition, cyt-c release from SF mitochondria remains significantly lower than C mitochondria despite the increased rate of H2O2 generation in SF mitochondria. The decreased cyt-c release from SF may be also related to the increased proportion of the palmitic acid-enriched cardiolipin, due to the high availibilty of palmitic acid in SF liver. The enrichment of cardiolipin molecular species with palmitic acid makes cardiolipin more resistant to peroxidation, a mechanism involved in the dissociation of cyt-c from mitochondrial inner membrane. These results suggest that Pal-CoA may participate in the progression of NAFLD to more severe disease through mechanisms involving cyt-c release and mMPT, a key process of apoptosis.
Abstract
This paper introduces a deep learning based methodology for analyzing the self-assembled, fractal-like structures formed in evaporated droplets. To this end, an extensive image database of ...such structures of the plant extract
Viscum album Quercus
$$10^{-3}$$
10
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3
was used, prepared by three different mixing procedures (turbulent, laminar, and diffusion based). The proposed pattern analysis approach is based on two stages: (1) automatic selection of patches that exhibit rich texture along the database; and (2) clustering of patches in accordance with prevalent texture by means of a Dense Convolutional Neural Network. The fractality of the patterns in each cluster is verified through Local Connected Fractal Dimension histograms. Experiments with Gray-Level Co-Occurrence matrices are performed to determine the benefit of the proposed approach in comparison with well established image analysis techniques. For the investigated plant extract, significant differences were found between the production modalities; whereas the patterns obtained by laminar flow showed the highest fractal structure, the patterns obtained by the application of turbulent mixture exhibited the lowest fractality. Our approach is the first to analyze, at the pure image level, the clustering properties of regions of interest within a database of evaporated droplets. This allows a greater description and differentiation of the patterns formed through different mixing procedures.
New atra paspalum (Paspalum atratum Swallen) accessions were found to be differentially grazed by cattle, without differences in herbage accumulation and nutritive value. This study aimed to evaluate ...cattle preference, morphological and anatomical leaf traits, and their relationships at four sampling events. Five new atra paspalum accessions and the cultivar Cambá were used. The experimental unit was a 2 m × 2 m plot. Treatments were replicated four times in a completely randomized design. Cattle preference was determined in spring (December 2016 and 2017), summer (March 2017), and autumn (May 2017) using six steers Bos spp. that grazed the plots for 4 h on two consecutive days. Plant height, leaf‐blade length, leaf‐blade width, and the proportions of five leaf tissues at three leaf regions were measured at each date. The proportion of the leaf that is curved was measured in December 2017. Cattle preference was variable among accessions and sampling events. Some accessions were shorter, with shorter and more flexible leaves than Cambá (p < 0.05). The proportion of lignified tissues was greater during the spring (2016 and 2017) and summer (7%–23%) than in the autumn. One accession had the lowest proportion of lignified tissue in the warm season (8%–12%) but the highest during the fall (around 15%). The same accession had the fewest primary vascular bundles in the warm season. Cattle preference was negatively correlated with the proportion of lignified tissues, the number of primary vascular bundles, plant height, and leaf‐blade length. Cattle preference was affected by the growing season and reduced by greater presence of leaf structural tissue.
Core Ideas
Variability for cattle preference was observed among accessions of Paspalum atratum.
Plant height, leaf length, and the number of primary vascular bundles negatively affected cattle preference.
Cattle preference seemed to be limited by the fraction of leaf‐supporting tissue.
The purpose of this paper is to re-examine the relationship between grammars and processing systems in light of the various forms of experimental research (especially of an electrophysiological ...nature) that has been conducted in the last fifteen years or so. First, the notion of 'processing strategy' or 'heuristics processing' is considered followed by a discussion of structures of great morphosyntactic complexity that parsing systems seem to tackle by simply respecting complex grammatical laws, instead of by resorting to shortcuts. Then, grammatical illusions and what these can teach us about the processing of grammar are considered. It is argued that illusions allow us to discern a few explanatory principles that may redefine the way we see parser-grammar relations. Among these is the idea that how long illusions last in the online-to-offline transition depends in part on their 'templatability', that is, the ease with which they become gestaltic templates. Another key idea is that some apparent illusions are in fact nothing more than grammar contemplated at work as in slow motion.
Recurrent selection methods have been successful in generating superior Paspalum notatum families through the accumulation of favorable alleles. However, the effectiveness of these methods in ...producing apomictic hybrids with superior agronomic traits has not been thoroughly evaluated. The aim of this study was to characterize the reproductive behavior of P. notatum progenies obtained through recurrent selection based on combining ability (RSCA) and recurrent phenotypic selection (RPS) and assess the performance of the apomictic hybrids concerning various agronomic traits. The reproductive mode of 144 RSCA and 144 RPS hybrids was determined using a molecular marker tightly linked to the apospory trait (BCU243‐377). The expressivity of apospory was estimated observing mature embryo sacs. The apomictic hybrids were then evaluated for six agronomic traits. A segregation ratio of 5:1 between sexual and apomictic hybrids was observed for the RSCA progeny, while 4.3:1 was registered for the RPS progeny. Although apospory expressivity was variable among hybrids, 75% and 86% of the RSCA and RPS hybrids, respectively, exhibited a high expression (>81%). Non‐significant differences between breeding methods in the number of apomictic hybrids and the level of apospory expressivity were observed. Variations for all agronomic traits were observed among apomictic hybrids within each breeding method. However, no differences between methods in the performance of the highly apomictic hybrids were observed. This demonstrates that the reproductive behavior of P. notatum is not affected by the recurrent selection method. Therefore, the RPS method would be the most suitable since it was equally effective than RSCA but it is cheaper, faster, and easier to apply.
Core Ideas
Highly apomictic hybrids with superior forage attributes were obtained by recurrent selection in Paspalum notatum.
The proportion of apomictic hybrids was not affected by the recurrent selection method.
Recurrent phenotypic selection would be the most suitable method for breeding Paspalum notatum.
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•Total extracts of D. winteri, L. tupa, V. foetida and V. portalesia showed insecticidal activity against S. granarius.•Extracts of D. winteri caused the mortality of 87% of insects; ...L. tupa 80%, V. foetida 56% meanwhile V. portalesia of insects at concentration of 2.5%w/w in diets, over 6-days.•Active compounds were isolated from D. winteri giving polygodial, drimenol and drimenin, meanwhile lobelanidine was obtained from L. tupa.•Pure compounds showed concentration dependent toxicity against S. granarius at 0.5% w/w polygodial and drimenol caused the 80% of the insect mortality meanwhile lobelanidine caused 46.7% and drimenin only 20%, after 6 days.
Extracts and compounds from the Chilean plants canelo, Drimys winteri J.R. Forst. & G. Forst. (Winteraceae), tabaco del diablo, Lobelia tupa L. (Campanulaceae), huevil, Vestia foetida Hoffmans. (Solanaceae) and violeta, Viola portalesia Gay (Violaceae) were evaluated against Sitophilus granarius L. (Coleoptera: Curculionidae), one of the most widespread and destructive primary pests of stored cereals. Total extracts at concentrations of 2.5%w/w in diets, over 6-days, display insecticidal effects against S. granarius. D. winteri caused the mortality of 87.5% of insects; L. tupa 80%, V. foetida 56% whereas V. portalesia killed 45% of insects under the same conditions. In an effort to determine the active compounds, the extracts of Lobelia tupa and Drimys winteri were purified by preparative chromatography. The piperidine alkaloid lobelanidine was isolated from L. tupa and the drimane sesquiterpenes drimenin, drimenol and polygodial were isolated as the major components in the extract from D. winteri. The purified compounds compounds displayed insecticidal activity against S. granarius in a concentration/dependent-time manner (% mortality at 0.5%w/w over 6-days): polygodial 80%, drimenol 60%, lobelanidine 47%, and drimenin 20%. In agreement with these results, grains treated with polygodial showed greater protection against the feeding attack by the granary weevil. These results provide evidence of the importance of elements of the native Chilean flora as new potential sources of botanical pesticides for the insect pest control.
Ethnopharmacological relevance:
Pien-Tze-Huang (PZH)—a traditional Chinese medicine (TCM) compound—has been employed to treat various liver inflammation and tumors for over 10 decades. Interestingly, ...most of the pharmacological effects had been validated and explored toward liver ailment along with pro-inflammatory conditions and cancer at the cellular and molecular level to date.
Aim of the study:
The present study aimed to investigate the therapeutic effect of PZH on autophagy and TGF-β1 signaling pathways in rats with liver fibrosis and hepatic stellate cell line (HSC).
Materials and methods:
Male SD rats with carbon tetrachloride (CCl4)-induced liver fibrosis were used as the animal model. Next, PZH treatment was given for 8 weeks. Afterward, the therapeutic effects of PZH were analyzed through a hepatic tissue structure by hematoxylin-eosin (H&E), Van Gieson (VG) staining, and transmission electron microscopy (TEM), activity of ALT and AST by enzyme-associated immunosorbent assay as well. Subsequently, mRNA and protein expression were examined by quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry (IHC). Then, the cell vitality of PZH-treated HSC and the expression of key molecules prevailing to autophagy were studied
in vitro.
Meanwhile, SM16 (a novel small molecular inhibitor which inhibits TGFβ-induced Smad2 phosphorylation) was employed to confirm PZH’s effects on the proliferation and autophagy of HSC.
Results:
PZH pharmacologically exerted anti-hepatic fibrosis effects as demonstrated by protecting hepatocytes and improving hepatic function. The results revealed the reduced production of extracellular collagen by adjusting the balance of matrix metalloproteinase (MMP) 2, MMP9, and tissue inhibitor of matrix metalloproteinase 1 (TIMP1) in PZH-treated CCl4-induced liver fibrosis. Interestingly, PZH inhibited the activation of HSC by down-regulating TGF-β1 and phosphorylating Smad2. Furthermore, PZH down-regulated yeast Atg6 (Beclin-1) and microtubule-associated protein light chain 3 (LC3) toward suppressing HSC autophagy, and PZH exhibited similar effects to that of SM16.
Conclusion:
To conclude, PZH alleviated CCl4-induced liver fibrosis to reduce the production of extracellular collagen and inhibiting the activation of HSC. In addition, their pharmacological mechanisms related to autophagy and TGF-β1/Smad2 signaling pathways were revealed for the first time.
•The genetic progress was positive for lint yield and for the main yield components.•The rate of increase in lint yield was 3.24 kg.ha−1.y−1 (p < 0.01, r2 = 0.5).•Lint yield and its components were ...primarily explained by environmental.•Almost all the studied variables were positively correlated with lint yield.
The Argentinian cotton (Gossypium hirsutum L.) breeding program was established in 1923 and since then it has released more than 40 commercial cultivars of cotton and numerous germplasm lines. Genetic progress studies have been used to evaluate the historical enhancement of different traits and to provide insights into possible improvements in future cultivars. In this context, the present study aims to estimate the genetic progress for lint yield (LY) and its components among cotton cultivars released in Argentina since 1965 throughout different environmental conditions and to determine correlations among agronomic traits. This study was conducted over a 2-year period and included 20 cotton cultivars grown in four different environments through different sowing dates. Genetic progress in LY was 3.24 kg.ha−1.y−1 with no differences among environments. The LY improvement was accompanied by a significant increase in seed cotton yield (SCY), lint percentage (LP), number of boll. m−2 (NB) and lint.seed−1 (LS). The environment was the dominant factor governing LY and its main components, except for LP where genotype was the dominating factor. Pearson correlation showed that LY, SCY, BN, boll weight, lint.boll-1, number seed.boll-1, and seed index were positively correlated. The information obtained from this study would be an important tool for crop management and breeding programs for high yielding cotton.
This study analyzes the existence of the added worker effect (AWE) when a male partner suffers a health shock (negative health event), by using the information from the Chilean Social Protection ...Survey. The health shocks considered in this study are new cases of arthritis, asthma and hypertension. We find that neither asthma nor hypertension diagnosis generates an AWE. In the case of arthritis, the study shows differentiated effects by age cohorts. More specifically, we find that women's probability of labor force entry over three years increases by 50 percentage points when the husband between the ages of 18-44 is diagnosed with arthritis. This effect disappears in older age groups, which suggests that when studying the effect of health shocks, the differences between life cycle stages should be considered (chronic disabling conditions are an important source of financial risk for young households).
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