Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double‐blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24–34 weeks gestational age) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n = 31) or placebo supplemented (n = 29) preterm infants. Term peers (n = 30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p < 0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33 to 4.09 wt% or 2.88 to 3.55 mol%, p < 0.0001) while placebo‐supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35 to 3.32 wt% or 2.91 to 2.87 mol%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97 wt% or 4.31 mol%) at discharge (p = 0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.     

Scaling Effects in Perovskite Ferroelectrics: Fundamental Limits and Process‐Structure‐Property Relations

Ferroelectric materials are well‐suited for a variety of applications because they can offer a combination of high performance and scaled integration. Examples of note include piezoelectrics to transform between electrical and mechanical energies, capacitors used to store charge, electro‐optic devices, and nonvolatile memory storage. Accordingly, they are widely used as sensors, actuators, energy storage, and memory components, ultrasonic devices, and in consumer electronics products. Because these functional properties arise from a noncentrosymmetric crystal structure with spontaneous strain and a permanent electric dipole, the properties depend upon physical and electrical boundary conditions, and consequently, physical dimension. The change in properties with decreasing physical dimension is commonly referred to as a size effect. In thin films, size effects are widely observed, whereas in bulk ceramics, changes in properties from the values of large‐grained specimens is most notable in samples with grain sizes below several micrometers. It is important to note that ferroelectricity typically persists to length scales of about 10 nm, but below this point is often absent. Despite the stability of ferroelectricity for dimensions greater than ~10 nm, the dielectric and piezoelectric coefficients of scaled ferroelectrics are suppressed relative to their bulk counterparts, in some cases by changes up to 80%. The loss of extrinsic contributions (domain and phase boundary motion) to the electromechanical response accounts for much of this suppression. In this article, the current understanding of the underlying mechanisms for this behavior in perovskite ferroelectrics is reviewed. We focus on the intrinsic limits of ferroelectric response, the roles of electrical and mechanical boundary conditions, grain size and thickness effects, and extraneous effects related to processing. In many cases, multiple mechanisms combine to produce the observed scaling effects.     

Effect of Mechanical Constraint on Domain Reorientation in Predominantly {111}‐Textured Lead Zirconate Titanate Films

Ferroelectric/ferroelastic domain reorientation was measured in 2.0 μm thick tetragonal {111}‐textured PbZr_0.30Ti_0.70O₃ thin films using synchrotron X‐ray diffraction (XRD). Lattice strain from the peak shift in the 111 Bragg reflection and domain reorientation were quantified as a function of applied electric field amplitude. Domain reorientation was quantified through the intensity exchange between the 112 and 211 Bragg reflections. Results from three different film types are reported: dense films that are clamped to the substrate (as‐processed), dense films that are partially released from the substrate, and films with 3% volume porosity. The highest amount of domain reorientation is observed in grains that are misoriented with respect to the {111} preferred (domain engineered) orientation. Relative to the clamped films, films that were released from the substrate or had porosity exhibited neither significant enhancement in domain reorientation nor in 111 lattice strain. In contrast, similar experiments on {100}‐textured and randomly oriented films showed significant enhancement in domain reorientation in released and porous films. Therefore, {111}‐textured films are less susceptible to changes in properties due to mechanical constraints because there is overall less domain reorientation in {111} films than in {100} films.     

The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.     

Protein Kinases and Parkinson’s Disease

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.     

材料的重要性

《材料的重要性》是《景观设计理论》的一段节选。《景观设计理论》旨在不使用专业术语或其他领域假说的前提下,结合景观设计过程向学生介绍内在理论思想。《材料的重要性》是本书的五章之一。每一章针对特定理论,解释了其基础和来源,探讨了它对设计的重要性,列举了20—21世纪与其相关的设计案例,整理了该理论的辩论(尤其是有关现代和后现代思想),最后还有相关阅读材料清单和需要学生们思考的问题。本文分为如下3个部分：第一部分,物质性,介绍“辩证唯物主义”“媒介即信息”“物质实践”和“编码”等理论及其在设计中的运用;第二部分,通过“建构表达”“地貌代理人策略”“石材的面层”“材料的暗示”“人造,但不是伪造”等理论,介绍材料的真实性及其在设计中的运用;第三部分,复写理论及应用,包括“剩余物”“复写的展示性”“未来的复写”和“虚构的复写”等内容。     

The Effects of Annealing After Equal Channel Angular Extrusion (ECAE) on Mechanical and Magnetic Properties of 49Fe-49Co-2V Alloy

Metallurgical and Materials Transactions A - Equal channel angular extrusion (ECAE) of 49Fe-49Co-2V, also known as Hiperco® 50A or Permendur-2V, greatly improves the strength and ductility of...     

Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.     

Cross-Omics Analysis of Fenugreek Supplementation Reveals Beneficial Effects Are Caused by Gut Microbiome Changes Not Mammalian Host Physiology

Herbal remedies are increasing in popularity as treatments for metabolic conditions such as obesity and Type 2 Diabetes. One potential therapeutic option is fenugreek seeds (Trigonella foenum-graecum), which have been used for treating high cholesterol and Type 2 diabetes. A proposed mechanism for these benefits is through alterations in the microbiome, which impact mammalian host metabolic function. This study used untargeted metabolomics to investigate the fenugreek-induced alterations in the intestinal, liver, and serum profiles of mice fed either a 60% high-fat or low-fat control diet each with or without fenugreek supplementation (2% w/w) for 14 weeks. Metagenomic analyses of intestinal contents found significant alterations in the relative composition of the gut microbiome resulting from fenugreek supplementation. Specifically, Verrucomicrobia, a phylum containing beneficial bacteria which are correlated with health benefits, increased in relative abundance with fenugreek. Metabolomics partial least squares discriminant analysis revealed substantial fenugreek-induced changes in the large intestines. However, it was observed that while the magnitude of changes was less, significant modifications were present in the liver tissues resulting from fenugreek supplementation. Further analyses revealed metabolic processes affected by fenugreek and showed broad ranging impacts in multiple pathways, including carnitine biosynthesis, cholesterol and bile acid metabolism, and arginine biosynthesis. These pathways may play important roles in the beneficial effects of fenugreek.