Neue,hochechte organische pigmente

Malonic acid dianilides, which are readily obtainable from malonic ester and anilines, are suitable coupling components for the production of azo pigments, and yield, for example when using amino-anthraquinones as diazo components, pigments with in some cases excellent fastness values. The reaction of malonic ester with anthranilamide produces, under specific conditions, 2,2′-methylene-bis-4-hydroxyquinazoline, a new intermediate which is particularly suitable for the production of pigments.Anthraquinone azomethine pigments obtained from amino-anthraquinones and methylene-active intermediates can easily be produced; for example, using orthoformic acid esters. By reaction with methylene-bis-4-hydroxy-quinazolines, β-hydroxynaphthoic acid anilides, dihydroxyquinolines and pyridones, new, deeply coloured, azomethine pigments, often with excellent fastness values, are thereby obtained.     

3-Methylglutaconic Aciduria Type I Due to AUH Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature

3-Methylglutaconic aciduria type I (MGCA1) is an inborn error of the leucine degradation pathway caused by pathogenic variants in the AUH gene, which encodes 3-methylglutaconyl-coenzyme A hydratase (MGH). To date, MGCA1 has been diagnosed in 19 subjects and has been associated with a variable clinical picture, ranging from no symptoms to severe encephalopathy with basal ganglia involvement. We report the case of a 31-month-old female child referred to our center after the detection of increased 3-hydroxyisovalerylcarnitine levels at newborn screening, which were associated with increased urinary excretion of 3-methylglutaconic acid, 3-hydroxyisovaleric acid, and 3-methylglutaric acid. A next-generation sequencing (NGS) panel for 3-methylglutaconic aciduria failed to establish a definitive diagnosis. To further investigate the strong biochemical indication, we measured MGH activity, which was markedly decreased. Finally, single nucleotide polymorphism array analysis disclosed the presence of two microdeletions in compound heterozygosity encompassing the AUH gene, which confirmed the diagnosis. The patient was then supplemented with levocarnitine and protein intake was slowly decreased. At the last examination, the patient showed mild clumsiness and an expressive language disorder. This case exemplifies the importance of the biochemical phenotype in the differential diagnosis of metabolic diseases and the importance of collaboration between clinicians, biochemists, and geneticists for an accurate diagnosis.     

Activation capability of water soluble organic substances as CCN

The activation capability of seven dicarboxylic acid compounds, ammonium oxalate, malonic acid, succinic acid, glutaric acid, adipic acid, malic acid and phthalic acid, was determined by laboratory experiments, and predictability by the Köhler theory was discussed. Experimental results showed that ammonium oxalate had the highest capability comparable to that of ammonium sulfate, and malic acid and phthalic acid followed, whereas adipic acid exhibited the lowest capability close to that of an insoluble particle. Malonic acid and glutaric acid were considered to evaporate under normal experimental operations at 8–9% RH but exhibited high and moderate capability, respectively, under supplementary humid operations. The activation capability of succinic acid tended to depend on the laboratory temperatures but was possibly high, comparable to that of malic acid. Particulate drying, associated solute vaporization, morphology and hydrophobicity of particles could be key factors in the theoretical prediction and the interpretation of the experimental results.     

Synthesis and in situ foaming of biodegradable malonic acid ESO polymers

In this study, biodegradable rigid cellular materials were synthesized from the reaction of malonic acid with epoxidized soybean oil. Malonic acid reacts with two epoxy groups to give a network polymer. In the course of this reaction, initially formed malonic acid monoester (MAME) can decarboxylate and produce CO₂, which acts as the blowing agent leading to in situ foaming of the polymer. Epoxide addition and decarboxylation reactions of MAME occur competitively and simultaneously and by controlling their relative rates, foams of controlled density were produced. ¹H NMR spectrum of the synthesized foams showed that increasing the temperature increases the rate of decarboxylation reaction of MAME and decreases crosslink density leading to softer and lower density foams. Addition of 1,4‐diazabicyclo[2.2.2]octane (DABCO) as a catalyst also increases the rate of decarboxylation. Load deflection curves of the cellular materials showed that decreasing the temperature and addition of DABCO increase compressive modulus of samples. Cell morphology was studied by microscopic images of foam samples that showed that foam samples have a closed cell structure and a wide distribution of cell volume. Soil burial test was done to determine rate of biodegradation of foam samples. A half‐life of 815 days showed that foam samples are highly biodegradable. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Selective transport of a cupric-nickel-cobalt ion ternary system through cation ion-exchange membranes with a complexing agent by dialysis

The selective transport behaviors of metal ions for a ternary ion system through a cation-exchange membrane were studied in a stirred batch dialyzer. Cu⁺²-Ni⁺²-Co⁺² was chosen for the experiment. Malonic acid, oxalic acid and citric acid were employed as the complexing agent used in the solution in order to increase the discrepancy between transport fluxes of metal ions. The experimental results show that the order of effective complexing agents is citric acid> malonic acid > oxalic acid. The stoichiometric ratio of complexing agent to metal ions and the pH value of the feed solution are the primary factors on the selective transport behavior of metal ions. The optimal results of P_Co-Na:P_Ni-Na: P_{Cu_Na} can be attained about 5.40:3.75:0.75. A theoretical model of the system was formulated on the basis of the Nernst-Planck equation and interface equilibrium hypothesis. Theoretical solutions obtained by numerical calculation were in agreement with the results within a 15% deviation.     

CACNA1A Mutations Causing Early Onset Ataxia: Profiling Clinical,Dysmorphic and Structural-Functional Findings

The CACNA1A gene encodes the pore-forming α_1A subunit of the voltage-gated Ca_V2.1 Ca²⁺ channel, essential in neurotransmission, especially in Purkinje cells. Mutations in CACNA1A result in great clinical heterogeneity with progressive symptoms, paroxysmal events or both. During infancy, clinical and neuroimaging findings may be unspecific, and no dysmorphic features have been reported. We present the clinical, radiological and evolutionary features of three patients with congenital ataxia, one of them carrying a new variant. We report the structural localization of variants and their expected functional consequences. There was an improvement in cerebellar syndrome over time despite a cerebellar atrophy progression, inconsistent response to acetazolamide and positive response to methylphenidate. The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge. The two α_1A affected residues are fully conserved throughout evolution and among the whole human Ca_V channel family. They contribute to the channel pore and the voltage sensor segment. According to structural data analysis and available functional characterization, they are expected to exert gain- (F1394L) and loss-of-function (R1664Q/R1669Q) effect, respectively. Among the CACNA1A-related phenotypes, our results suggest that non-progressive congenital ataxia is associated with developmental delay and dysmorphic features, constituting a recognizable syndromic neurodevelopmental disorder.     

Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease

Besides serving as a structural membrane component and intermediate of the glycerolipid metabolism, lysophosphatidic acid (LPA) has a prominent role as a signaling molecule through its binding to LPA receptors at the cell surface. Extracellular LPA is primarily produced from lysophosphatidylcholine (LPC) through the activity of secreted lysophospholipase D, autotaxin (ATX). The degradation of extracellular LPA to monoacylglycerol is mediated by lipid phosphate phosphatases (LPPs) at the cell membrane. This review summarizes and interprets current literature on the role of the ATX-LPA-LPP3 axis in the regulation of energy homeostasis, insulin function, and adiposity at baseline and under conditions of obesity. We also discuss how the ATX-LPA-LPP3 axis influences obesity-related metabolic complications, including insulin resistance, fatty liver disease, and cardiomyopathy.     

Deficient Leptin Cellular Signaling Plays a Key Role in Brain Ultrastructural Remodeling in Obesity and Type 2 Diabetes Mellitus

The triad of obesity, metabolic syndrome (MetS), Type 2 diabetes mellitus (T2DM) and advancing age are currently global societal problems that are expected to grow over the coming decades. This triad is associated with multiple end-organ complications of diabetic vasculopathy (maco-microvessel disease), neuropathy, retinopathy, nephropathy, cardiomyopathy, cognopathy encephalopathy and/or late-onset Alzheimer’s disease. Further, obesity, MetS, T2DM and their complications are associated with economical and individual family burdens. This review with original data focuses on the white adipose tissue-derived adipokine/hormone leptin and how its deficient signaling is associated with brain remodeling in hyperphagic, obese, or hyperglycemic female mice. Specifically, the ultrastructural remodeling of the capillary neurovascular unit, brain endothelial cells (BECs) and their endothelial glycocalyx (ecGCx), the blood-brain barrier (BBB), the ventricular ependymal cells, choroid plexus, blood-cerebrospinal fluid barrier (BCSFB), and tanycytes are examined in female mice with impaired leptin signaling from either dysfunction of the leptin receptor (DIO and db/db models) or the novel leptin deficiency (BTBR ob/ob model).     

Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats

Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.     

Effects of malonic acid treatment on crystal structure,melting behavior,morphology, and mechanical properties of isotactic poly(propylene)/wollastonite composites

Wollastonite is treated with a new surface modifier (malonic acid). The influence of malonic acid treatment on the crystallization and mechanical properties of polypropylene (PP)/wollastonite composites has been studied. The results of differential scanning calorimetry, wide angle X‐ray diffractometry, and polarized light microscopy prove that malonic acid‐treated wollastonite increases the relative content of β‐crystal form of PP. The scanning electron microscopy shows that malonic acid‐treated wollastonite has better compatibility with PP matrix than the untreated wollastonite. Higher β‐phase contents, smaller spherulite sizes, and better compatibility with PP matrix of the composites containing malonic acid‐treated wollastonite result in improved impact strength and tensile strength, but lower flexural modulus. The results of Fourier transform infrared spectroscopy show that malonic acid reacts with the Ca²⁺ of wollastonite to form the calcium malonate, which acts as an effective β‐nucleating agent. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineers     

Function and Regulation of microRNA171 in Plant Stem Cell Homeostasis and Developmental Programing

MicroRNA171 (miR171), a group of 21-nucleotide single-strand small RNAs, is one ancient and conserved microRNA family in land plants. This review focuses on the recent progress in understanding the role of miR171 in plant stem cell homeostasis and developmental patterning, and the regulation of miR171 by developmental cues and environmental signals. Specifically, miR171 regulates shoot meristem activity and phase transition through repressing the HAIRY MERISTEM (HAM) family genes. In the model species Arabidopsis, miR171 serves as a short-range mobile signal, which initiates in the epidermal layer of shoot meristems and moves downwards within a limited distance, to pattern the apical-basal polarity of gene expression and drive stem cell dynamics. miR171 levels are regulated by light and various abiotic stresses, suggesting miR171 may serve as a linkage between environmental factors and cell fate decisions. Furthermore, miR171 family members also demonstrate both conserved and lineage-specific functions in land plants, which are summarized and discussed here.     

Biomarkers in Glycogen Storage Diseases: An Update

Glycogen storage diseases (GSDs) are a group of 19 hereditary diseases caused by a lack of one or more enzymes involved in the synthesis or degradation of glycogen and are characterized by deposits or abnormal types of glycogen in tissues. Their frequency is very low and they are considered rare diseases. Except for X-linked type IX, the different types are inherited in an autosomal recessive pattern. In this study we reviewed the literature from 1977 to 2020 concerning GSDs, biomarkers, and metabolic imbalances in the symptoms of some GSDs. Most of the reported studies were performed with very few patients. Classification of emerging biomarkers between different types of diseases (hepatics GSDs, McArdle and PDs and other possible biomarkers) was done for better understanding. Calprotectin for hepatics GSDs and urinary glucose tetrasaccharide for Pompe disease have been approved for clinical use, and most of the markers mentioned in this review only need clinical validation, as a final step for their routine use. Most of the possible biomarkers are implied in hepatocellular adenomas, cardiomyopathies, in malfunction of skeletal muscle, in growth retardation, neutropenia, osteopenia and bowel inflammation. However, a few markers have lost interest due to a great variability of results, which is the case of biotinidase, actin alpha 2, smooth muscle, aorta and fibroblast growth factor receptor 4. This is the first review published on emerging biomarkers with a potential application to GSDs.     

Cardiomyopathies: An Overview

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were “cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome”. Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological.     

Amberlyst 70磺酸树脂催化合成丙二酸二乙酯

以Amberlyst 70磺酸树脂为催化剂催化丙二酸与乙醇的酯化反应,合成重要的精细化工中间体丙二酸二乙酯。考察反应时间、反应温度、醇酸物质的量比、催化剂用量等对酯化反应的影响,优化反应条件。结果表明,在醇酸物质的量比为3∶1、催化剂用量为丙二酸质量的10%、反应时间2 h和反应温度120℃的条件下,丙二酸二乙酯产率和选择性98.9%。表明Amberlyst 70磺酸树脂对丙二酸与乙醇的酯化反应有较高的催化活性。     

Synthesis and characterization of malonic acid-doped polyaniline

The conductive form of polyaniline was synthesized by the anodic and chemical oxidation of aniline in malonic acid medium. The conductivity of polyaniline doped with malonic acid changed from 1.62×10–6 to 2.5×10–5Scm–1 depending on the way it was synthesized. The polymer growth rate was observed to be very slow in malonic acid compared with H2SO4. Thermogravimetric data revealed that the maximum thermal reaction rate of PANI doped with malonic acid was at 200°C and 520°C compared with 290°C and 530°C of the polymer doped with H2SO4.     

Investigation of poly(β-malic acid)synthesis pathways and regulation by strains of Aureobasidium pulluans

The possible biosynthesis pathways of poly(β-malic acid)(PMLA)and the feasible approaches to regulating PMLA production in A. pullulans BS24 were studied.To investigate the effects of the metabolic inhibitors of tricarboxylic acid cycle(TCA)cycle on PMLA fermentation,supplementation of the inhibitors to the medium was implemented.The results demonstrated that trifluoroacetic acid inhibited PMLA production,but malonic acid and maleic acid promoted PMLA production and isocitrate lyase activity.It could be concluded that PMLA synthesis was related to the TCA cycle and glyoxylate pathway in A. pullulans.Based on this result,the method of facilitating the accumulation of PMLA via metabolic intermediates was further designed.The medium containing 3.0 g·L^-1 fumaric acid or 1.5 g·L^-1 L-malic acid was used.Isocitrate lyase activity was increased by 18.39% and 25.30%,respectively.And the two added intermediates also increased the activity of L-malate dehydrogenase and fumarase,while reduced the activity of isocitrate dehydrogenase and α-ketoglutaric acid dehydrogenanse,and the final PMLA yield was increased by 46.58% and 43.70%,respectively.The metabolic intermediates could modify the redistribution of metabolic flux between TCA cycle and glyoxylate pathway,therefore,carbon source could be efficiently used to synthesize PMLA.     

Cerebrospinal Fluid Metabolome in Parkinson’s Disease and Multiple System Atrophy

Parkinson’s disease (PD) and multiple system atrophy (MSA) belong to the neurodegenerative group of synucleinopathies; differential diagnosis between PD and MSA is difficult, especially at early stages, owing to their clinical and biological similarities. Thus, there is a pressing need to identify metabolic biomarkers for these diseases. The metabolic profile of the cerebrospinal fluid (CSF) is reported to be altered in PD and MSA; however, the altered metabolites remain unclear. We created a single network with altered metabolites in PD and MSA based on the literature and assessed biological functions, including metabolic disorders of the nervous system, inflammation, concentration of ATP, and neurological disorder, through bioinformatics methods. Our in-silico prediction-based metabolic networks are consistent with Parkinsonism events. Although metabolomics approaches provide a more quantitative understanding of biochemical events underlying the symptoms of PD and MSA, limitations persist in covering molecules related to neurodegenerative disease pathways. Thus, omics data, such as proteomics and microRNA, help understand the altered metabolomes mechanism. In particular, integrated omics and machine learning approaches will be helpful to elucidate the pathological mechanisms of PD and MSA. This review discusses the altered metabolites between PD and MSA in the CSF and omics approaches to discover diagnostic biomarkers.     

出芽短梗霉积累聚苹果酸途径及调控研究

引言聚苹果酸[poly(β-malic acid),PMLA]是新近开发的一种生物高聚物,因其良好的水溶性、生物可降解性、生物相容性以及易代谢性[1]、易修饰性[2],PMLA及其衍生物在生物医用材料、化妆     

The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress,Inflammation and Apoptosis

Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.     

The role of retinoids and their receptors in metabolic disorders

Retinoid derivatives are potent regulators of a wide variety of cellular functions through the modulation of nuclear receptor activity. Three distinct families of retinoid receptors have been identified so far, namely retinoic acid receptors, retinoic acid X receptors, and retinoic acid‐related orphan receptors. This review focuses on retinoid signaling and the regulation of metabolic processes by the family of retinoic acid receptors in relation to the development of metabolic disorders.