Search Results (36)

The synergistic solvent extraction of La(III), Eu(III) and Lu(III) with a chelating extractant, 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HL), and neutral bidentate heterocyclic amines, such as 1,10-phenanthroline (S1 (phen)) or 2,2′-bipyridine (S2 (bipy)) in an ionic liquid of the imidazolium family [C₁C₄im⁺][Tf₂N⁻] was investigated. Synergistic effects have been observed to result from the formation of a ternary complex in the organic phase, particularly in cases where the ligand S is a neutral synergistic agent. Examples include La(L)₂(S2)₂, Eu(L)₃(S2) and Lu(L)_x(S2)₂, as well as La(L)₃(S1)₂, Eu(L)₂(S1) and Lu(L)₃(S1)_x). The parameters of the solvent extraction process were determined and the influence of the synergistic agent on the extraction process was discussed. Additionally, the synergistic increase and separation factors were determined. The equilibrated organic phases were analyzed using ¹H NMR spectroscopy to elucidate the synergism in an extraction mechanism. The role of the ionic diluent in complexation processes and selectivity was investigated with the employment of the two synergistic agents for various metal s-, p-, d- and f-cations in the periodic table, with almost 22 metal ions. Full article

Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease with two distinct phenotypes, an infantile-onset form (formerly Wolman disease) and a later-onset form (formerly cholesteryl ester storage disease). The objective of this narrative review is to examine the most important aspects of the diagnosis and treatment of LAL-D and to provide practical expert recommendations. The infantile-onset form occurs in the first weeks of life and is characterized by malnourishment and failure to thrive due to gastrointestinal impairment (vomiting, diarrhea, malabsorption), as well as systemic inflammation, hepatosplenomegaly, and adrenal calcifications. Mortality is close to 100% before one year of life in the absence of specific treatment. The later-onset form can be diagnosed in childhood or adulthood and is characterized by chronic liver injury and/or lipid profile alterations. When LAL-D is suspected, enzyme activity should be determined to confirm the diagnosis, with analysis from a dried blood spot sample being the quickest and most reliable method. In infantile-onset LAL-D, the initiation of enzyme replacement therapy (sebelipase α) and careful nutritional management with a low-lipid diet is very urgent, as prognosis is directly linked to the early initiation of specific treatment. In recent years, our knowledge of the management of LAL-D has increased considerably, with improvements regarding the initial enzyme replacement therapy dose and careful nutritional treatment with a low-lipid diet to decrease lipid deposition and systemic inflammation, leading to better outcomes. In this narrative review we offer a quick guide for the initial management of infantile-onset LAL-D. Full article

Lysosomal acid lipase (LAL) is the only known enzyme that degrades cholesteryl esters and triglycerides at an acidic pH. In LAL deficiency (LAL-D), dysregulated expression of matrix metalloproteinase 12 (MMP-12) has been described. The overexpression of MMP-12 in myeloid lineage cells causes an immune cell dysfunction resembling that of Lal knockout (Lal KO) mice. Both models develop progressive lymphocyte dysfunction and expansion of myeloid-derived suppressor (CD11b+ Gr-1+) cells. To study whether MMP-12 might be a detrimental contributor to the pathology of LAL-D, we have generated Lal/Mmp12 double knockout (DKO) mice. The phenotype of Lal/Mmp12 DKO mice closely resembled that of Lal KO mice, while the weight and morphology of the thymus were improved in Lal/Mmp12 DKO mice. Cytological examination of blood smears showed a mildly reversed lymphoid-to-myeloid shift in DKO mice. Despite significant decreases in CD11b+ Ly6G+ cells in the peripheral blood, bone marrow, and spleen of Lal/Mmp12 DKO mice, the hematopoietic bone marrow progenitor compartment and markers for neutrophil chemotaxis were unchanged. Since the overall severity of LAL-D remains unaffected by the deletion of Mmp12, we conclude that MMP-12 does not represent a viable target for treating the inflammatory pathology in LAL-D. Full article

The Early Pleistocene sites of Orce in southeastern Spain, including Fuente Nueva-3 (FN3), Barranco León (BL) and Venta Micena (VM), provide important insights into the earliest hominin populations and Late Villafranchian large mammal communities. Dated to approximately 1.4 million years ago, FN3 and BL preserve abundant Oldowan tools, cut marks and a human primary tooth, indicating hominin activity. VM, approximately 1.6 million years old, is an outstanding site because it preserves an exceptionally rich assemblage of large mammals and predates the presence of hominins, providing a context for pre-human conditions in the region. Research suggests that both hominins and giant hyenas were essential to the accumulation of skeletal remains at FN3 and BL, with secondary access to meat resources exploited by saber-toothed felids. This aim of this study aims to correlate the relative abundance of large herbivores at these sites with their estimates of Carrying Capacity (CC) and Total Available Biomass (TAB) using the PSEco model, which incorporates survival and mortality profiles to estimate these parameters in paleoecosystems. Our results show: (i) similarities between quarries VM3 and VM4 and (ii) similarities of these quarries with BL-D (level D), suggesting a similar formation process; (iii) that the role of humans would be secondary in BL-D and FN3-LAL (Lower Archaeological Level), although with a greater human influence in FN3-LAL due to the greater presence of horses and small species; and (iv) that FN3-UAL (Upper Archaeological Level) shows similarities with the expected CC values for FN3/BL, consistent with a natural trap of quicksand scenario, where the large mammal species were trapped according to their abundance and body mass, as there is a greater presence of rhinos and mammoths due to the greater weight per unit area exerted by their legs. Given the usefulness of this approach, we propose to apply it first to sites that have been proposed to function as natural traps. Full article

Lysosomal acid lipase deficiency (LALD) varies from a severe infantile-onset form (Wolman disease) to a late-onset form known as cholesteryl ester storage disease (CESD), both of which are autosomal recessive disorders caused by biallelic LIPA pathogenic variants. We evaluated seventy-three patients enlisted for liver transplant (LT) at Instituto da Criança (HCFMUSP—Brazil) who were subjected to LAL activity measurement and LIPA Sanger sequencing analysis, resulting in a positive LALD diagnosis for only one of these individuals. This LALD patient presented recurrent diarrhea, failure to thrive, hepatomegaly, and dyslipidemia at the age of 4 months and liver failure by the age of 13 years. The LALD diagnosis confirmation was conducted at 24 years old due to low levels of LAL enzyme activity. The causal homozygous variant LIPA(NM_000235.4):c.266T>C(p.Leu89Pro) was identified, but the patient had already undergone his first LT at 18 years with several rejection episodes. Despite beginning treatment with sebelipase alfa at 26 years old (total of five infusions), this patient died at 28 years from complications after his second liver transplant. LALD is an important differential diagnosis in cases presenting with hepatomegaly, elevated liver enzymes, and dyslipidemia. Detecting low/absent LAL activity and identifying the LIPA causal variant are essential for diagnosis and specific treatment, as well as for appropriate genetic counseling. Early diagnosis, along with sebelipase alfa therapy, may improve the prognosis of affected patients. Full article

Bamboos, also known as non-timber forest products (NTFPs) and belonging to the family Poaceae and subfamily Bambusoideae, have a wide range of flowering cycles from 3 to 120 years; hence, it is difficult to identify species. Here, the focus is on supervised machine learning (ML) and deep learning (DL) as a potential automated approach for the identification and classification of commercial bamboo species, with the help of the majority multiclass voting (MajMulVot) algorithm. We created an image dataset of 2000 bamboo instances, followed by a texture dataset prepared using local binary patterns (LBP) and gray-level cooccurrence matrix (GLCM)-based methods. First, we deployed five ML models for the texture datasets, where support vector machine (SVM) shows an accuracy rate of 82.27%. We next deployed five DL-based convolutional neural network (CNN) models for bamboo classification, namely AlexNet, VGG16, ResNet18, VGG19, and GoogleNet, using the transfer learning (TL) approach, where VGG16 prevails, with an accuracy rate of 88.75%. Further, a MajMulVot-based ensemble approach was introduced to improve the classification accuracy of all ML- and DL-based models. The ML-MajMulVot enhanced the accuracy for the texture dataset to 86.96%. In the same way, DL-MajMulVot increased the accuracy to 92.8%. We performed a comparative analysis of all classification models with and without K-fold cross-validation and MajMulVot methods. The proposed findings indicate that even difficult-to-identify species may be identified accurately with adequate image datasets. The suggested technology can also be incorporated into a mobile app to offer farmers effective agricultural methods. Full article

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 ± 10.1 years and a mean body-mass index (BMI) of 23.1 ± 1.7 kg/m². The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 ± 3.2, 21.7 ± 3.2, and 206.7 ± 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival. Full article

Indiscriminate and injudicious application of inorganic fertilizers and irrigation, respectively, cause declines in crop productivity as well as environmental pollution. Therefore, judicious use of organic manures and proper scheduling of irrigation are required for sustainable production of wheat crops. A two-year (2014–2015 and 2015–2016) study was conducted to determine the wheat nutrient uptake, soil moisture, and grain yield as a result of organic manures and irrigation schedule. The experiment was set up with four treatments of organic manure in four subplots with repellents and five irrigation planning treatments in the main plot. The results showed that an irrigation/water ratio of 0.9 irrigation water depth/cumulative pan evaporation (I₂) increased grain yield, soil moisture content, and nutrient uptake of wheat (I₃) compared to 0.6 IW/CPE during the vegetative period and 0.8 IW/CPE during the reproductive period. According to statistics, it was found that the vegetative period is maintained at 0.8 IW/CPE, and the reproductive period is maintained at 1.0 IW/CPE (I₅). Applying 7.5 Mg ha⁻¹ of farmyard manure (FYM) plus 3 Mg ha⁻¹ of vermicompost while employing organic manure increases grain output, soil moisture content, and nutrient content and absorption compared to the control treatment. Therefore, it is concluded that irrigation either at I₂ or I₅ + FYM at 7.5 Mg ha⁻¹ + vermicompost at 3 Mg ha⁻¹ could be recommended for enhancing grain of wheat cultivation, particularly in the semiarid regions of northwestern India. Full article

Antibiotic resistance has exponentially increased during the last years. It is necessary to develop new antimicrobial drugs to prevent and treat infectious diseases caused by multidrug- or extensively-drug resistant (MDR/XDR)-bacteria. Host Defense Peptides (HDPs) have a versatile role, acting as antimicrobial peptides and regulators of several innate immunity functions. The results shown by previous studies using synthetic HDPs are only the tip of the iceberg, since the synergistic potential of HDPs and their production as recombinant proteins are fields practically unexplored. The present study aims to move a step forward through the development of a new generation of tailored antimicrobials, using a rational design of recombinant multidomain proteins based on HDPs. This strategy is based on a two-phase process, starting with the construction of the first generation molecules using single HDPs and further selecting those HDPs with higher bactericidal efficiencies to be combined in the second generation of broad-spectrum antimicrobials. As a proof of concept, we have designed three new antimicrobials, named D5L37βD3, D5L37D5L37 and D5LAL37βD3. After an in-depth exploration, we found D5L37D5L37 to be the most promising one, since it was equally effective against four relevant pathogens in healthcare-associated infections, such as methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis (MRSE) and MDR Pseudomonas aeruginosa, being MRSA, MRSE and P. aeruginosa MDR strains. The low MIC values and versatile activity against planktonic and biofilm forms reinforce the use of this platform to isolate and produce unlimited HDP combinations as new antimicrobial drugs by effective means. Full article

Erosion by water reduces soil quality and hence crop yield. Understanding the response of crop yields to soil erosion is vital in assessing agriculture’s vulnerability to erosion. However, these effects are difficult to quantify. The study presents a quantitative relationship between soil erosion and soil quality and productivity of rainfed wheat (Triticum aestivum) by comparing field plots with different degrees of erosion in some sub-tropical alfisols in the Doon Valley region of India. By comparing the topsoil depth with the reference site as the control, erosion severity was classified into different phases such as slight, moderate, severe, and very severe. A quantitative, weighted additive model was used to evaluate soil quality for different phases of erosion using soil clay content, water holding capacity, soil aggregate, soil organic carbon, pH, CEC, total N, available P, and available K. The synthesis of long-term experimental data revealed that the mean soil erosion rate varied from 5.5 Mg ha⁻¹ yr⁻¹ in slightly eroded plots to 33.4 Mg ha⁻¹ yr⁻¹ in very severely eroded plots. Compared with the reference forest, the soil organic carbon (SOC) declined by 81.4% and water holding capacity by 31% in severely eroded soils. A substantial loss of total N, extractable P, and available K was also observed. Water stable aggregates (WSA) decreased from 86% to 12.6%, and the cation exchange capacity (CEC) from 25 to 12.6 c mol⁽⁺⁾ kg⁻¹. The soil quality index was 0.7 in slightly eroded compared with 0.4 in severely eroded soil. Similarly, the sustainable yield index for wheat was 0.9 and 0.6 for slightly and severely eroded soils, respectively. Thus, there is a strong need to identify land management systems that reduce erosion risks, restore eroded soils, and enhance soil quality. Full article

Although nitrogen (N) is the most limiting nutrient for agricultural production, its overuse is associated with environmental pollution, increased concentration of greenhouse gases, and several human and animal health implications. These implications are greatly affected by biochemical transformations and losses of N such as volatilization, leaching, runoff, and denitrification. Half of the globally produced N fertilizers are used to grow three major cereals—rice, wheat, and maize—and their current level of N recovery is approximately 30–50%. The continuously increasing application of N fertilizers, despite lower recovery of cereals, can further intensify the environmental and health implications of leftover N. To address these implications, the improvement in N use efficiency (NUE) by adopting efficient agronomic practices and modern breeding and biotechnological tools for developing N efficient cultivars requires immediate attention. Conventional and marker-assisted selection methods can be used to map quantitative trait loci, and their introgression in elite germplasm leads to the creation of cultivars with better NUE. Moreover, gene-editing technology gives the opportunity to develop high-yielding cultivars with improved N utilization capacity. The most reliable and cheap methods include agronomic practices such as site-specific N management, enhanced use efficiency fertilizers, resource conservation practices, precision farming, and nano-fertilizers that can help farmers to reduce the environmental losses of N from the soil–plant system, thus improving NUE. Our review illuminates insights into recent advances in local and scientific soil and crop management technologies, along with conventional and modern breeding technologies on how to increase NUE that can help reduce linked N pollution and health implications. Full article

Lysosomal acid lipase (LAL) is a lysosomal enzyme essential for the degradation of cholesteryl esters through the endocytic pathway. Deficiency of the LAL enzyme encoded by the LIPA gene leads to LAL deficiency (LAL-D) (OMIM 278000), one of the lysosomal storage disorders involving 50–60 genes. Among the two disease subtypes, the severe disease subtype of LAL-D is known as Wolman disease, with typical manifestations involving hepatomegaly, splenomegaly, vomiting, diarrhea, and hematopoietic abnormalities, such as anemia. In contrast, the mild disease subtype of this disorder is known as cholesteryl ester storage disease, with hypercholesterolemia, hypertriglyceridemia, and high-density lipoprotein disappearance. The prevalence of LAL-D is rare, but several treatment options, including enzyme replacement therapy, are available. Accordingly, a number of screening methodologies have been developed for this disorder. This review summarizes the current discussion on LAL-D, covering genetics, screening, and the tertiary structure of human LAL enzyme and preclinical study for the future development of a novel therapy. Full article

Lipid droplet is a dynamic organelle that undergoes periods of biogenesis and degradation under environmental stimuli. The excessive accumulation of lipid droplets is the major characteristic of non-alcoholic fatty liver disease (NAFLD). Moderate aerobic exercise is a powerful intervention protecting against the progress of NAFLD. However, its impact on lipid droplet dynamics remains ambiguous. Mice were fed with 15 weeks of high-fat diet in order to induce NAFLD. Meanwhile, the mice performed 15 weeks of treadmill exercise. Our results showed that 15 weeks of regular moderate treadmill exercise alleviated obesity, insulin intolerance, hyperlipidemia, and hyperglycemia induced by HFD. Importantly, exercise improved histological phenotypes of NAFLD, including hepatic steatosis, inflammation, and locular ballooning, as well as prevented liver fat deposition and liver injury induced by HFD. Exercise reduced hepatic lipid droplet size, and moreover, it reduced PLIN2 protein level and increased PLIN3 protein level in the liver of HFD mice. Interestingly, our results showed that exercise did not significantly affect the gene expressions of DGAT1, DGAT2, or SEIPIN, which were involved in TG synthesis. However, it did reduce the expressions of FITM2, CIDEA, and FSP27, which were major involved in lipid droplet growth and budding, and lipid droplet expansion. In addition, exercise reduced ATGL protein level in HFD mice, and regulated lipophagy-related markers, including increasing ATG5, LAMP1, LAMP2, LAL, and CTSD, decreasing LC3II/I and p62, and promoting colocalization of LAMP1 with LDs. In summary, our data suggested that 15 weeks of moderate treadmill exercise was beneficial for regulating liver lipid droplet dynamics in HFD mice by inhibiting abnormal lipid droplets expansion and enhancing clearance of lipid droplets by lysosomes during the lipophagic process, which might provide highly flexible turnover for lipid mobilization and metabolism. Abbreviations: β-actin: actin beta; ATG5: autophagy related 5; LAMP2: lysosomal-associated membrane protein 2; LAMP1: lysosomal-associated membrane protein 1; SQSTM1/p62: sequestosome 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ATGL: adipose triglyceride lipase; CSTD: cathepsin D; LAL: lysosomal acid lipase; DGAT1: diacylglycerol-o-acyltransferase 1; DGAT2: diacylglycerol-o-acyltransferase 2; CIDEA: cell death inducing dffa-like effector a; CIDEC/FSP27: cell death inducing dffa-like effector c; FITM2: fat storage-inducing transmembrane protein 2; PLIN2: adipose differentiation related protein; PLN3: tail-interacting protein 47; HSP90: heat shock protein 90; SREBP1c: sterol regulatory element binding protein-1c; chREBP: carbohydrate response element binding protein. Full article

This study aimed to determine whether dissociative symptoms and childhood trauma (CT) may help identify a specific subgroup of patients among those hospitalized for alcohol use disorder (AUD). We assessed 587 patients hospitalized for an AUD in a French addiction rehabilitation center (cross-sectional study) regarding dissociative symptoms (DES-taxon), childhood trauma (CTQ), depression (BDI), anxiety (STAI-state and STAI-trait), posttraumatic stress disorder (PTSD; PCL-5), and AUD symptoms (AUDIT). We ran a hierarchical cluster analysis and compared the clusters in terms of dissociation and CT, as well as AUD, depressive, anxiety, and PTSD symptoms. We identified three clusters of patients: (1) patients with low AUD severity and low dissociation (LALD); (2) patients with high AUD severity and low dissociation (HALD); (3) patients with high AUD severity and high dissociation (HAHD). Patients from the HAHD group had significantly higher dissociation and more severe depression, anxiety, and PTSD symptoms than those with LALD and HALD. They also reported more emotional and sexual abuse than those with LALD. Among patients with an AUD, those with high dissociation may constitute an independent subgroup that exhibits a higher prevalence for CT and higher AUD severity, as well as higher depression, anxiety, and PTSD symptoms. Patients with more severe AUD and associated psychiatric symptoms should be systematically screened for dissociation and provided with tailor-based treatments. Full article

Gestational diabetes mellitus (GDM) during pregnancy is a marker for future type 2 diabetes mellitus (T2DM); therefore, a meticulous follow-up after delivery can help identify women at risk for T2DM. In a cohort of 5504 pregnant women, the postpartum follow-up of all 1043 women with GDM for hyperglycemia in a multi-ethnic, high-risk Arab population was investigated. The prevalence of GDM was 18.9%. A total of 265 (25.4%) women returned for an oral glucose tolerance test (OGTT) 4–6 weeks after delivery, with more South Asian than Arab women (p < 0.01). The other factors associated with return were (a) family history of T2DM, (b) lower basic metabolic index, (c) higher abortions and (d) lower gravida (p < 0.05), all with minimal effect. An abnormal postpartum OGTT was statistically associated with previous GDM history and hypoglycemic drug treatment, although these effects were small. Overall, the follow-up of women with GDM postpartum was dismal, ethnicity being the major factor influencing return. Urgent public measures are needed to educate women with GDM about follow-up highlighting (a) risk awareness for T2DM and (b) a healthy lifestyle after childbirth—if we are to turn the tide on the epidemic of T2DM plaguing the Arab world. Full article