Apolipoprotein E and Alzheimer's disease

Genetic variation in apolipoprotein E (APOE) influences Alzheimer's disease (AD) risk. APOE ε4 alleles are the strongest genetic risk factor for late onset sporadic AD. The AD risk is dose dependent, as those carrying one APOE ε4 allele have a 2–3-fold increased risk, while those carrying two ε4 alleles have a 10–15-fold increased risk. Individuals carrying APOE ε2 alleles have lower AD risk and those carrying APOE ε3 alleles have neutral risk. APOE is a lipoprotein which functions in lipid transport, metabolism, and inflammatory modulation. Isoform specific effects of APOE within the brain include alterations to Aβ, tau, neuroinflammation, and metabolism. Here we review the association of APOE with AD, the APOE isoform specific effects within brain and periphery, and potential therapeutics.     

Method for tissue clearing: temporal tissue optical clearing

Light absorption and scattering in biological tissue are significant variables in optical imaging technologies and regulating them enhances optical imaging quality. Optical clearing methods can decrease light scattering and improve optical imaging quality to some extent but owing to their limited efficacy and the potential influence of optical clearing agents on tissue functioning, complementing approaches must be investigated. In this paper, a new strategy of optical clearing proposed as time-dependent or temporal tissue optical clearing (TTOC) is described. The absorption and scattering in light interaction with tissue are regulated in the TTOC technique by altering the pulse width. Here, the dependence of optical properties of matter on the pulse width in a gelatin-based phantom was investigated experimentally. Then, a semi-classical model was introduced to computationally study of Ultra-short laser/matter interaction. After studying phantom, the absorption and scattering probabilities in the interaction of the pulse with modeled human skin tissue were investigated using the proposed model for pulse widths ranging from 1µs to 10fs. The propagation of the pulse through the skin tissue was simulated using the Monte Carlo technique by computing the pulse width-dependent optical properties (absorption coefficient µ_a, scattering coefficient µ_s, and anisotropy factor g). Finally, the penetration depth of light into the tissue and reflectance for different pulse widths was found.     

Enzymatic hydrolysis of low temperature alkali pretreated wheat straw using immobilized β-xylanase nanoparticles

A low temperature alkali (LTA) pretreatment method was used to treat wheat straw. In order to obtain good results, different factors like temperature, incubation time, NaOH concentration and solid to liquid ratio for the pretreatment process were optimized. Wheat straw is a potential biomass for the production of monomeric sugars. The objective of the current study was to observe the saccharification (%) of wheat straw with immobilized magnetic nanoparticles (MNPs). For this purpose, immobilized MNPs of purified β-xylanase enzyme was used for hydrolysis of pretreated wheat straw. Wheat straw was pretreated using the LTA method and analyzed by SEM analysis. After completion of the saccharification process, saccharification% was calculated by using a DNS method. Scanning electron micrographs revealed that the hemicellulose, cellulose and lignin were partially removed and changes in the cell wall structure of the wheat straw had caused it to become deformed, increasing the specific surface area, so more fibers of the wheat straw were exposed to the immobilized β-xylanase enzyme after alkali pretreatment. The maximum saccharification potential of wheat straw was about 20.61% obtained after pretreatment with optimized conditions of 6% NaOH, 1/10 S/L, 30 °C and 72 hours. Our results indicate the reusability of the β-xylanase enzyme immobilized magnetic nanoparticles and showed a 15% residual activity after the 11th cycle. HPLC analysis of the enzyme-hydrolyzed filtrate also revealed the presence of sugars like xylose, arabinose, xylobiose, xylotriose and xylotetrose. The time duration of the pretreatment has an important effect on thermal energy consumption for the low-temperature alkali method.

A low temperature alkali (LTA) pretreatment method was used to treat wheat straw.     

Profitable Fischer Tropsch realization via CO2–CH4 reforming; an overview of nickel–promoter–support interactions

Environmental pollution, climate change, and fossil fuel extinction have aroused serious global interest in the search for alternative energy sources. The dry reforming of methane (DRM) could be a good technique to harness syngas, a starting material for the FT energy process from greenhouse gases. Noble metal DRM catalysts are effective for the syngas generation but costly. Therefore, they inevitably, must be replaced by their Ni-based contemporaries for economic reasons. However, coking remains a strong challenge that impedes the industrialization of the FT process. This article explains the secondary reactions that lead to the production of detrimental graphitic coke deposition on the surface of active nickel catalyst. The influence of nickel particle size, impact of extra surface oxygen species, interaction of Ni catalysts with metal oxide supports/promoters, and larger fraction of exposed nickel active sites were addressed in this review. Size of active metal determines the conversion, surface area, metal dispersion, surface reactions, interior diffusion effects, activity, and yield. The influence of oxygen vacancy and coke deposition on highly reported metal oxide supports/promoters (Al₂O₃, MgO and La₂O₃) was postulated after studying CIFs (crystallographic information files) obtained from the Crystallography open database (COD) on VESTA software. Thus, overcoming excessive coking by La₂O₃ promotion is strongly advised in light of the orientation of the crystal lattice characteristics and the metal–support interaction can be used to enhance activity and stability in hydrogen reforming systems.

Particle size increases during agglomeration, which causes catalyst deactivation. Reducible metal oxide restricts metal growth, hence reducing the sintering.     

Functional polyamine metabolic enzymes and pathways encoded by the virosphere

Viruses produce more viruses by manipulating the metabolic and replication systems of their host cells. Many have acquired metabolic genes from ancestral hosts and use the encoded enzymes to subvert host metabolism. The polyamine spermidine is required for bacteriophage and eukaryotic virus replication, and herein, we have identified and functionally characterized diverse phage- and virus-encoded polyamine metabolic enzymes and pathways. These include pyridoxal 5′-phosphate (PLP)-dependent ornithine decarboxylase (ODC), pyruvoyl-dependent ODC and arginine decarboxylase (ADC), arginase, S-adenosylmethionine decarboxylase (AdoMetDC/speD), spermidine synthase, homospermidine synthase, spermidine N-acetyltransferase, and N-acetylspermidine amidohydrolase. We identified homologs of the spermidine-modified translation factor eIF5a encoded by giant viruses of the Imitervirales. Although AdoMetDC/speD is prevalent among marine phages, some homologs have lost AdoMetDC activity and have evolved into pyruvoyl-dependent ADC or ODC. The pelagiphages that encode the pyruvoyl-dependent ADCs infect the abundant ocean bacterium Candidatus Pelagibacter ubique, which we have found encodes a PLP-dependent ODC homolog that has evolved into an ADC, indicating that infected cells would contain both PLP- and pyruvoyl-dependent ADCs. Complete or partial spermidine or homospermidine biosynthetic pathways are found encoded in the giant viruses of the Algavirales and Imitervirales, and in addition, some viruses of the Imitervirales can release spermidine from the inactive N-acetylspermidine. In contrast, diverse phages encode spermidine N-acetyltransferase that can sequester spermidine into its inactive N-acetyl form. Together, the virome-encoded enzymes and pathways for biosynthesis and release or biochemical sequestration of spermidine or its structural analog homospermidine consolidate and expand evidence supporting an important and global role of spermidine in virus biology.

The polyamine spermidine (Fig. 1) is a metabolically primordial polycation found throughout bacteria, archaea, and eukaryotes (1). It is a fundamental molecule of life that was likely present in the last universal common ancestor (2). In Escherichia coli, 90% of spermidine is noncovalently bound to RNA (3) and is required for efficient translational elongation by the ribosome (4). Spermidine increases global messenger RNA (mRNA) translation in E. coli by facilitating the queuosine modification of specific tRNA anticodon wobble bases (4). Consistent with these findings, in strains of E. coli deleted for genes that modify the anticodon wobble position in transfer RNAs (tRNAs), spermidine becomes absolutely essential for growth (5), which may be due to spermidine-mediated stabilization of the tRNA interaction with the translating ribosome. Spermidine is not only important for growth of bacteria; over 40 y ago, it was shown that T4 and T7 bacteriophages replicated more slowly in a spermidine-deficient mutant of E. coli (6). Replication of JG004 and N4-like phages in Pseudomonas aeruginosa PAO1 is absolutely dependent on spermidine (7, 8).Open in a separate windowFig. 1.Polyamine metabolic pathways. Pathways biochemically characterized herein are indicated by blue arrows and blue enzyme names.In eukaryotic cells, spermidine is universally required for growth and cell proliferation. An aminobutyl moiety of spermidine (Fig. 1) is transferred by deoxyhypusine synthase (DHS) to a single lysine of the translation factor eIF5A to eventually form the essential hypusine posttranslational modification (9). Hypusinated eIF5a is needed for translation of mRNAs encoding proline-rich motifs and for translation termination (10). Replication of eukaryotic RNA viruses is highly dependent on host spermidine (11), and spermidine-derived hypusination of host eIF5a is required for Ebola virus replication and is considered a potential target to inhibit viral replication (12).Viruses reprogram the metabolism of host cells to make more virions by redirecting expression and activity of host-encoded enzymes and by expressing virus-encoded enzymes. Using homology-based approaches, nucleocytoplasmic large DNA viruses have been found to encode homologs of enzymes involved in nitrogen metabolism, glycolysis, and the tricarboxylic acid cycle (13). Bacteriophages have been found to encode homologs of enzymes involved in inorganic sulfur metabolism (14) and nucleotide metabolism (15). The eukaryotic chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) encodes an entire functional biosynthetic pathway for production of homospermidine (Fig. 1), a structural analog of spermidine, consisting of L-arginine decarboxylase (ADC), agmatine deiminase/iminohydrolase (AIH), N-carbamoylputrescine amidohydrolase (NCPAH), and homospermidine synthase (HSS) (16–18). In addition, PBCV-1 encodes a polyamine N-acetyltransferase (19). A biochemically functional HSS enzyme is encoded by Ralstonia phage ϕRSL1 (20). Considering the importance of polyamines to phage and virus replication, we sought to systematically identify and functionally characterize polyamine metabolic enzymes and pathways encoded in phage and virus genomes. Some of the taxonomic affiliations of giant viruses included in our study are based on a recently published hierarchical taxonomy for the Nucleocytoviricota (21).     

Phytochemicals That Act on Synaptic Plasticity as Potential Prophylaxis against Stress-Induced Depressive Disorder

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.     

Effect of clofibrate on reducing neonatal jaundice: a systematic review and meta-analysis

In neonates, bilirubin tends to be deposited in body tissues, especially the skin and mucous membranes. Jaundice is an early symptom of bilirubin excretion disorders. Therefore, the aim of this study was to investigate the effect of clofibrate on reducing neonatal jaundice. In this systematic review, international databases, including PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar, were searched without time and language restrictions. The reference lists of all studies ultimately included were manually searched. In the 17 articles reviewed, with a sample size of 665 people published between 2005 and 2019, the average weight of the neonates varied from 2,186 g to 4,000 g. Furthermore, the average age of neonates varied from 2 days to 9 days. Four doses of clofibrate (25, 30, 50, 100 mg/kg of neonatal body weight) were used. The bilirubin level of neonates significantly decreased in the intervention group 24, 36, 48, and 72 hours after the start of treatment. Clofibrate administration decreased total serum bilirubin, especially from the second day onwards, and also reduced hospitalization time, hospital costs, and side effects from hospitalization.     

Exploring the Barriers and Motivators to Dietary Adherence among Caregivers of Children with Disorders of Amino Acid Metabolism (AAMDs): A Qualitative Study

Dietary intervention is generally accepted as the mainstay of treatment for patients with disorders of amino acid metabolism (AAMDs). However, dietary adherence to a low-protein diet is always reported as a common challenge among these patients. This study explored the perception of barriers and motivators to dietary adherence among caregivers of AAMD patients in Malaysia. Twenty caregivers of children with AAMDs receiving ongoing treatment at the genetic clinic participated in an online focus group discussion from November to December 2021. Findings showed a total of five interrelated main themes identified from focus group discussion (FGD) exploring parents’ experiences related to the management of their child’s daily diet. The barriers to dietary adherence were burden of dietary treatment, diet and dietary behavior, parenting challenges, limited knowledge related to dietary treatment, and challenges in healthcare system delivery. Key factors facilitating good dietary adherence include good knowledge of dietary treatment, parental coping strategies, social coping, and dietary behavior. In conclusion, despite the existence of several barriers to the implementation of dietary treatment, caregivers managed to use a wide range of coping strategies to overcome some, if not all, of the challenges. The important next step is to develop, in conjunction with multidisciplinary healthcare professionals, feasible implementation strategies that could address these barriers and at the same time improve the quality of life of caregivers.     

Tomonaga–Luttinger Spin Liquid and Kosterlitz–Thouless Transition in the Spin-1/2 Branched Chains: The Study of Topological Phase Transition

In the present work, we provide a comprehensive numerical investigation of the magnetic properties and phase spectra of three types of spin-1/2 branched chains consisting of one, two and three side spins per unit block with intra-chain interaction and a uniform inter-chain interaction in the presence of an external magnetic field. In a specific magnetic field interval, the low-temperature magnetization of these chains shows a step-like behavior with a pronounced plateau depending on the strength and the type of intra-chain interaction being ferromagnetic or antiferromagnetic. We demonstrate that when inter-chain interaction J1 is antiferromagnetic and intra-chain interaction J2 is ferromagnetic, the magnetization of the models manifests a smooth increase without a plateau, which is evidence of the existence of a Luttinger-like spin liquid phase before reaching its saturation value. On the other hand, when J1 is ferromagnetic and J2 is antiferromagnetic, the low-temperature magnetization of the chain with two branches shows an intermediate plateau at one-half of the saturation magnetization that breaks a quantum spin liquid phase into two regions. The magnetization of the chain with three branches exhibits two intermediate plateaus and two regions of a quantum spin liquid. We demonstrate that the chains with more than one side spin illustrate in their ground-state phase diagram a Kosterlitz–Thouless transition from a gapful phase to a gapless spin liquid phase.     

Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus (MRSA)

This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to conf...