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Diets rich in carbohydrate and saturated fat contents, when combined with a sedentary lifestyle, contribute to the development of obesity and metabolic syndrome (MetS), which subsequently increase palmitic acid (PA) levels. At high concentrations, PA induces lipotoxicity through several mechanisms involving endoplasmic reticulum (ER) stress, mitochondrial dysfunction, inflammation and cell death. Nevertheless, there are endogenous strategies to mitigate PA-induced lipotoxicity through its unsaturation and elongation and its channeling and storage in lipid droplets (LDs), which plays a crucial role in sequestering oxidized lipids, thereby reducing oxidative damage to lipid membranes. While extended exposure to PA promotes mitochondrial reactive oxygen species (ROS) generation leading to cell damage, acute exposure of ß-cells to PA increases glucose-stimulated insulin secretion (GSIS), through the activation of free fatty acid receptors (FFARs). Subsequently, the activation of FFARs by exogenous agonists has been suggested as a potential therapeutic strategy to prevent PA-induced lipotoxicity in ß cells. Moreover, some saturated fatty acids, including oleic acid, can counteract the negative impact of PA on cellular health, suggesting a complex interaction between different dietary fats and cellular outcomes. Therefore, the challenge is to prevent the lipid peroxidation of dietary unsaturated fatty acids through the utilization of natural antioxidants. This complexity indicates the necessity for further research into the function of palmitic acid in diverse pathological conditions and to find the main therapeutic target against its lipotoxicity. The aim of this review is, therefore, to examine recent data regarding the mechanism underlying PA-induced lipotoxicity in order to identify strategies that can promote protection mechanisms against lipotoxicity, dysfunction and apoptosis in MetS and obesity.

Genus Salvia is considered one of the largest genera of family Lamiaceae with many recorded species and hybrids of valuable biological importance. This study involved the phytochemical characterization of four Salvia hybrids (KNM23 (S. fructicosa × S. officinalis), KNM101 (S. aramiensis × S. officinalis), KNM5 (S. aramiensis × S. officinalis) and KNM12 (S. fructicosa × S. officinalis)) through measuring their total phenolic content (TPC) and total flavonoid content (TFC) together with profiling through UPLC/MSn analysis followed by investigation of their antioxidant activities and enzyme inhibitory potential through different techniques. Hybrid KNM23 presented significantly high concentration of both phenolic and flavonoid, displaying a TPC of 92.10 mg GAE/g and a TFC of 50.85 mg RE/g. The UPLC/MSn profiling resulted in the tentative identification of one hundred eighty components from different phytochemical classes mainly flavonoids, phenolic acids, phenyl propanoids, tannins and many others. The antioxidant assay showed that hybrid KNM23, a hybrid of S. fruticosa and S. officinalis, exhibited the highest antioxidant activity in the DPPH, ABTS, and PBD assays, measuring 436.38 mmol TE/g, 543.65 mmol TE/g, and 3.20 mmol TE/g, respectively. KNM23 and KNM12 showed no inhibition of AChE and α‐glucosidase. However, KMN12 demonstrated highest BChE and tyrosinase 2.57 mg GALAE/g and 12.91 mg KAE/g, respectively. Our results suggest that the Salvia hybrids can be considered as natural sources of bioactive compounds in the development of health‐promoting applications. It can be concluded that, genus Salvia, as one of the well‐known and phytochemically rich genera of family Lamiaceae, served here as a source of four hybrids which were evaluated as a potential source of biologically important metabolites

Lane detection is an important module for active safety systems since it increases safety and reduces traffic accidents caused by driver inattention. Illumination changes or occlusions make lane detection a challenging task, especially if the detection is performed from a single image. Consequently, this paper presents a probabilistic approach based on the Kalman filter, which uses information from previous image frames to estimate the lane that could not be detected in the current image frame, considering uncertainty in the prediction as well as in the detection. To this end, a principal component analysis of the segmented curvature is introduced with the purpose of dimensionality reduction, moving from a large dimensional pixel representation to a considerably reduced space representation. Furthermore, the proposed approach is compared with a fully connected pretrained CNN model for lane detection, demonstrating that the proposed method has a lower computational cost in addition to a smoother transition between lane estimates.

Fil: Marcón, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina

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.

Approximately 90% of children with cancer live in low-income and middle-income countries (LMICs), where 5-year survival is lower than 20%. Treatment-related mortality in high-income countries is approximately 3–5%; however, in LMICs, treatment-related mortality has been reported in up to 45% of children with cancer. This study aimed to systematically explore the burden of treatment-related mortality in children with cancer in LMICs and to explore the association between country income level and treatment-related mortality. For this systematic review and meta-analysis we identified articles published between Jan 1, 2010, and June 22, 2021, describing treatment-related mortality in paediatric patients (aged 0–21 years) with cancer in LMICs. We searched PubMed, Trip, Web of Science, Embase, and the WHO Global Metric Index databases. The search was limited to full-text articles and excluded case reports (<10 patients) and haematopoietic stem-cell transplantation recipients. Two reviewers independently screened studies for eligibility, extracted data from included publications, and evaluated data quality. Random and mixed-effects models were used to estimate treatment-related mortality burden and trends. The Cochran-Q statistic was used to assess heterogeneity between studies. This study is registered on PROSPERO (CRD42021264849). Of 13 269 identified abstracts, 501 studies representing 68 351 paediatric patients with cancer were included. The treatment-related mortality estimate was 6·82% (95% CI 5·99–7·64), accounting for 30·9% of overall mortality (4437 of 14 358 deaths). Treatment-related mortality was inversely related to country income. Treatment-related mortality was 14·19% (95% CI 9·65–18·73) in low-income countries, 9·21% (7·93–10·49) in lower-middle-income countries, and 4·47% (3·42–5·53) in upper-middle-income countries (Cochran-Q 42·39, p<0·0001). In upper-middle-income countries, the incidence of treatment-related mortality decreased over time (slope –0·002, p=0·0028); however, outcomes remained unchanged in low-income (p=0·21) and lower-middle-income countries (p=0·16). Approximately one in 15 children receiving cancer treatment in LMICs die from treatment-related complications. Although treatment-related mortality has decreased in upper-middle-income countries over time, it remains unchanged in LMICs. There is an urgent need for targeted supportive care interventions to reduce global disparities in childhood cancer survival. American Lebanese Syrian Associated Charities and National Cancer Institute.

Various types of motion introduced into a solution can affect, among other factors, the alignment and positioning of molecules, the agglomeration of large molecules, oxidation processes, and the production of microparticles and microbubbles. We employed turbulent mixing vs. laminar flow induced by a vortex vs. diffusion-based mixing during the production of Viscum album Quercus L. 10 −3 following the guidelines for manufacturing homeopathic preparations. The differently mixed preparation variants were analyzed using the droplet evaporation method. The crystalline structures formed in dried droplets were photographed and analyzed using computer-supported image analysis and deep learning. Computer-supported evaluation and deep learning revealed that the patterns of the variant succussed under turbulence are characterized by lower complexity, whereas those obtained from the vortex-mixed variant are characterized by greater complexity compared to the diffusion-based mixed control variant. The droplet evaporation method could provide a relatively inexpensive means of testing the effects of liquid flow and serve as an alternative to currently used methods.

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 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.

In the past decades, the grasses of the Paspalum genus have emerged as a versatile model allowing evolutionary, genetic, molecular, and developmental studies on apomixis as well as successful breeding applications. The rise of such an archetypal system progressed through integrative phases, which were essential to draw conclusions based on solid standards. Here, we review the steps adopted in Paspalum to establish the current body of knowledge on apomixis and provide model breeding programs for other agronomically important apomictic crops. In particular, we discuss the need for previous detailed cytoembryological and cytogenetic germplasm characterization; the establishment of sexual and apomictic materials of identical ploidy level; the development of segregating populations useful for inheritance analysis, positional mapping, and epigenetic control studies; the development of omics data resources; the identification of key molecular pathways via comparative gene expression studies; the accurate molecular characterization of genomic loci governing apomixis; the in-depth functional analysis of selected candidate genes in apomictic and model species; the successful building of a sexual/apomictic combined breeding scheme.

Key message Transcriptomics- and FAME-GC-MS-assisted apomixis breeding generated Paspalum notatum hybrids with clonal reproduction and increased α-linolenic acid content, offering the potential to enhance livestock product's nutritional quality and reduce methane emissions A low omega-6:omega-3 fatty acid ratio is considered an indicator of the nutritional impact of milk fat on human health. In ruminants, major long-chain fatty acids, such as linoleic acid (18:2, omega-6) and α-linolenic acid (18:3, omega-3), originate from dietary sources and reach the milk via the bloodstream. Since forages are the primary source of long-chain fatty acids for such animals, they are potential targets for improving milk lipid composition. Moreover, a high 18:3 content in their diet is associated with reduced methane emissions during grazing. This work aimed to develop genotypes of the forage grass Paspalum notatum with high leaf 18:3 content and the ability for clonal reproduction via seeds (apomixis). We assembled diploid and polyploid Paspalum notatum leaf transcriptomes and recovered sequences of two metabolism genes associated with the establishment of lipid profiles, namely SUGAR-DEPENDENT 1 ( SDP1 ) and PEROXISOMAL ABC TRANSPORTER 1 ( PXA1 ). Primers were designed to amplify all expressed paralogs in leaves. qPCR was used to analyse SDP1 and PXA1 expression in seven divergent genotypes. Reduced levels of SDP1 and PXA1 were found in the polyploid sexual genotype Q4188. Fatty acid methyl esters/gas chromatography/mass spectrometry (FAME/GC/MS) assays confirmed an increased percentage of 18:3 in this genotype. Crosses between Q4188 and the obligate apomictic pollen donor Q4117 resulted in two apomictic F 1 hybrids (JS9 and JS71) with reduced SDP1 and PXA1 levels, increased 18:3 content, and clonal maternal reproduction. These materials could enhance milk and meat quality while reducing greenhouse gas emissions during grazing.