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Apolipoprotein ε allele 4 (APOE4) influences the metabolism of polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). The entorhinal cortex (EC) in the brain is affected early in Alzheimer's disease and is rich in DHA. The purpose of this study is to identify the effect of APOE4 and DHA lipid species on the EC. Plasma and cerebrospinal fluid (CSF) lipidomic measurements were obtained from the DHA Brain Delivery Pilot, a randomized clinical trial of DHA supplementation (n = 10) versus placebo (n = 12) for six months in nondemented older adults stratified by APOE4 status. Wild-type C57B6/J mice were fed a high or low DHA diet for 6 months followed by plasma and brain lipidomic analysis. Levels of phosphatidylcholine DHA (PC 38:6) and cholesterol ester DHA (CE 22:6) had the largest increases in CSF following supplementation (P < 0.001). DHA within triglyceride (TG) lipids in CSF strongly correlated with corresponding plasma TG lipids, and differed by APOE4, with carriers having a lower increase than noncarriers. Changes in plasma PC DHA had the strongest association with changes in EC thickness in millimeters, independent of APOE4 status (P = 0.007). In mice, a high DHA diet increased PUFAs within brain lipids. Our findings demonstrate an exchange of DHA at the CSF-blood barrier and into the brain within all lipid species with APOE having the strongest effect on DHA-containing TGs. The correlation of PC DHA with EC suggests a functional consequence of DHA accretion in high density lipoprotein for the brain.

Abstract Background Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer’s disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. Methods CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. Results Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. Conclusions Treatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain.

Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs) and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1β or tumor necrosis factor α elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1β. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration.

Comparative analyses of neuronal phenotypes in closely related species can shed light on neuronal changes occurring during evolution. The study of post-mortem brains of nonhuman primates (NHPs) has been limited and often does not recapitulate important species-specific developmental hallmarks. We utilize induced pluripotent stem cell (iPSC) technology to investigate the development of cortical pyramidal neurons following migration and maturation of cells grafted in the developing mouse cortex. Our results show differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos both in vitro and in vivo, suggesting heterochronic changes in human neurons. The strategy proposed here lays the groundwork for further comparative analyses between humans and NHPs and opens new avenues for understanding the differences in the neural underpinnings of cognition and neurological disease susceptibility between species.

Comparative analyses of neuronal phenotypes in closely related species can shed light on neuronal changes occurring during evolution. The study of post-mortem brains of nonhuman primates (NHPs) has been limited and often does not recapitulate important species-specific developmental hallmarks. We utilize induced pluripotent stem cell (iPSC) technology to investigate the development of cortical pyramidal neurons following migration and maturation of cells grafted in the developing mouse cortex. Our results show differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos both in vitro and in vivo, suggesting heterochronic changes in human neurons. The strategy proposed here lays the groundwork for further comparative analyses between humans and NHPs and opens new avenues for understanding the differences in the neural underpinnings of cognition and neurological disease susceptibility between species.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an extended polyglutamine repeat in the N terminus of the Huntingtin protein (HTT). Reactive microglia and elevated cytokine levels are observed in the brains of HD patients, but the extent to which neuroinflammation results from extrinsic or cell-autonomous mechanisms in microglia is unknown. Using genome-wide approaches, we found that expression of mutant Huntingtin (mHTT) in microglia promoted cell-autonomous pro-inflammatory transcriptional activation by increasing the expression and transcriptional activities of the myeloid lineage-determining factors PU.1 and C/EBPs. We observed elevated levels of PU.1 and its target genes in the brains of mouse models and individuals with HD. Moreover, mHTT-expressing microglia exhibited an increased capacity to induce neuronal death ex vivo and in vivo in the presence of sterile inflammation. These findings suggest a cell-autonomous basis for enhanced microglia reactivity that may influence non-cell-autonomous HD pathogenesis.

Maize is a popular staple food among the urban population of South Sudan. However, due to inadequate food safety surveillance and enforcement systems, there is limited information on the aflatoxin safety of maize grains at farm and market levels. Therefore, this study aimed at assessing aflatoxins awareness and handling practices of maize grains among randomly selected farmers (n=30) and traders (n=30) as well as determining the moisture content, Aspergillus species counts and aflatoxins contamination. A cross-sectional descriptive study was carried out in Magwi maize producing areas, Juba retail/wholesale markets and Nimule border points of South Sudan. Moisture content, fungal and aflatoxins contamination in maize grain samples were determined using dry air oven method, dilution plating technique, and High-Performance Liquid Chromatography (HPLC), respectively. The respondent results showed that farmers (97%) and traders (83%) were unaware of aflatoxins. About 83% of the farmers dried their maize grains on tarpaulins, for 4 - 5 days (77%). In addition, most farmers (77%) stored their maize grain bags on raised platforms, whereas most traders (73%) stored grains on bare ground. All the maize grains met the required moisture content limit (below 13.5%). Maize from Nimule main park had the highest levels of contamination with Aspergillus flavus (9 log CFU/g), Aspergillus parasiticus (12 log CFU/g), aflatoxin B1 (505.56 µg/kg) and total aflatoxins (1,032.19 µg/kg). Maize from Gudele market was contaminated with Aspergillus parasiticus (12 log CFU/g), and aflatoxin B1 (76.55 µg/kg), and had a total aflatoxin content of 94.09 µg/kg. Omeo farmers' maize grains had the least levels of contamination of Aspergillus parasiticus (6 log CFU/g), aflatoxin B1 (4.39 µg/kg), and total aflatoxins (7.83 µg/kg). In addition, Aspergillus flavus was not detected from Omeo farmers' maize grains and no aflatoxins were detected from Agoro and Paluonganyi farmers' grains. This study recommends wider aflatoxins awareness and regular aflatoxin screening of maize grains by the relevant stakeholders in South Sudan. [ABSTRACT FROM AUTHOR]

By 2024, the global Internet user base is expected to reach 5.5 billion, with 94% actively engaging on social media platforms. Marketing managers increasingly employ strategies involving key opinion leaders to connect with Generation Z, a demographic known for its digital fluency and reliance on social networks. This study utilizes a qualitative approach to investigate how emotional attachment impacts Generation Z consumers’ trust in social media figures and its effect on impulsive buying behavior. It contributes to the body of knowledge on digital marketing by identifying factors that enhance the effectiveness of social media personalities in reaching and persuading Generation Z audiences. The findings provide actionable insights for content creators aiming to expand their following and for businesses seeking to strengthen their credibility and drive consumer purchasing decisions through collaboration with digital creators. The results reveal that emotional attachment to online personalities is a crucial driver of trust among Generation Z, significantly affecting their unplanned purchasing habits. Additionally, emotional connection acts as a catalyst, amplifying the impact of trust on spontaneous buying tendencies. Although trust in social media figures has a notable effect on unplanned purchasing, the relatively weak correlation underscores the need for further exploration of additional factors influencing Generation Z’s decision-making processes.

A summary of key discoveries regarding the industrial applications of impinging jets on a vertical plate. The summary explores the link between the dynamics and heat transmission on one hand and the relationship between heat exchange and acoustic coupling on the other hand. The objective of this research work is to investigate the vortex dynamics and heat transfer mechanisms in impinging jets. The jet impingement technique finds widespread use in the industry, it serves purposes such as drying, cooling, and heating. The impinging jet system involves directing a fluid jet with high-velocity onto a surface. The jet impingement results in high heat exchange rates and mass transfer rates, making it an attractive technique in various industrial processes. To investigate these mechanisms, a combination of experimental and computational methods was used, including flow visualization and numerical simulations. The study of vortex dynamics in impinging jets is crucial for understanding the heat transfer mechanisms involved. The flow characteristics of impinging jets, such as the Reynolds number (Re) of the jet, the distance from the blowing mouth to the impinged wall, and the geometry of the blowing mouth, significantly affect the vortex dynamics and heat transfer rates. Therefore, optimizing these parameters can result in significant improvements in heat transfer efficiency. Several methods were proposed to enhance heat transfer, these methods can affect the flow dynamic, the surface of impingement, the nozzle’s shape and size, and the impingement parameters such as the impact distance and the jet angle. For example, investigations have identified that optimal heat transfer took place at an inclination angle between 40 and 90 degrees. In addition, studies have reported enhancement in heat transfer with diamond orifices that reached up to 17%. The key findings of this paperwork include the identification of optimal impingement parameters that maximize heat transmission rates and the understanding of the significant relationship between the dynamics of the flow and the acoustic emissions. For instance, studies showed that synthetic jets can enhance convective heat transfer by 3 times compare to natural convection. The correlation between the flow dynamic and the heat transmission on one side, and the flow dynamics and acoustic emission on the other side, emphasizes the researcher to present acoustic-thermal coupled studies on the impinging jet; this topic needs more effort to understand the relation between the two phenomena. The conclusion highlights the significance of previous findings in industrial applications, suggesting control mechanisms capable of reducing noise and enhancing heat transmission.

Infant formula milk (IFM) is increasingly utilized as a substitute for natural breastfeeding despite the fact that breast milk has been always recognized as the optimal nourishment method. While IFMs are fortified with essential nutrients that are crucial for proper growth, they can also harbor non-essential toxic metal contaminants from various sources during the production process. Given the heightened vulnerability of newborns to such contaminants, it is imperative to thoroughly analyze, evaluate, and minimize the toxicity associated with the consumption of such IFMs. However, classical approaches to date, have been always adopted for assessing such risks by finding first the analytical concentration of metals in the IFMs followed by multiplying it by the average daily powder intake (ADI) then dividing by the average infant weight. The outcome is then compared to an established standard such a PTWI to assess the extent of toxicity. The drawback with such studies is the use of a fixed ADI for all samples as if all samples have the same and exact preparation directions while using somewhat different infant masses.Accordingly, this study aims at assessing the toxic risk amongst newborns from IFM consumption through the identification and application of various highly important and toxicity-contributing parameters from each IFM and its directions of preparation label separately which are discussed here for the first time while providing comparisons between the classical approach versus our new approach to highlight its importance.Seventy-three IFMs (0–6 months) were analyzed for lead (Pb), cadmium (Cd), arsenic (As), and aluminum (Al) levels and unlike previous studies, this work incorporated various feeding parameters from each IFM for calculating the intakes thus, revealing potential toxicity risks even in IFMs that are considered safe by the classical approach. Metal contamination was significant, with 97.3 % of samples containing detectable Pb, 41.1 % Cd, 16.4 % As, and 93.2 % Al while highlighting Pb in exceeding its maximum allowable level (MAL). This novel approach, which considers new diverse feeding schedules/parameters that are ironically suggested by manufacturers that have been previously overlooked elsewhere, emphasized IFMs' potential as sources of heightened metal toxicity in comparison to classical approaches. Results highlighted Pb and Al as major concerns, with As and Cd of lesser concern. Findings also emphasized the importance of such new parameters for safeguarding newborn health and should be payed attention to by caregivers. The study strongly and highly recommends adherence to minimum feeding schedules (MFS) and proper scooping techniques to reduce newborn exposure to toxic metals. It also suggests continuous monitoring and stricter regulations by health authorities at the production level of such products so as to provide a safer commodity in the first degree and to also provide better and somewhat uniform and specific feeding labels and precautions on such products.

In today's volatile business environment, manufacturers often face the challenge of making sales and production decisions despite unstable market demand. Companies must strategically determine which customer orders to fulfill or which products to stock under limited resources. This study addresses these challenges by proposing a mixed-integer mathematical programming model to optimize order acceptance/rejection and inventory decisions in a multi-period, multi-product hybrid make-to-order (MTO) and make-to-stock (MTS) system. The model incorporates various factors such as holding costs, production costs, stockout costs, budget constraints, production lead time, labor constraints, and order-specific costs. For each period, the model evaluates resource utilization, production lead times, and stock and stockout costs to decide production for stock or order acceptance/rejection. Additionally, it determines the optimal production quantities for stock and order fulfillment, as well as safety stock levels, all aimed at maximizing profit. To validate the proposed model, a real-life application was conducted using data from a chemical plant, exploring different scenarios to assess the model's sensitivity and capabilities. Furthermore, an experimental study examined the limitations of the mathematical model as the problem size increased, with test problems of varying dimensions developed to measure its effectiveness.

Abstract In this study, a glass microfibers interlayer (GMI) was used at the interface of the cathode and electrolyte in lithium‐sulfur batteries to prevent polysulfides loss from the cathode which contributes to capacity and coulombic efficiency fades during cycling. The interlayer's performance was evaluated using full‐cell studies and various visual experiments at commercially relevant sulfur areal loadings. Cells with sulfur loading of 4 mg cm−2 consistently had initial capacities exceeding 1200 mAh g−1 and reached a stable performance at around 900 mAh g−1 after 2 cycles at 2.23 mA cm−2. After 200 cycles the capacity retention remained robust at 95 %, marking an average decay rate of only 0.016 % per cycle. Cathodes with 2.8 mg cm−2 at 1.57 mA cm−2 rate and cathodes with 2 mg cm−2 at 3.3 mA cm−2 high rate exhibit improved rate capability and excellent stability over 400 cycles and 500 cycles respectively with 20 % more capacity retention than non‐GMI cells. Post‐failure analyses of the cell components revealed the GMI's role in controlling the concentration of soluble polysulfides at the anode and a suitable candidate that can be used alone or in tandem with other approaches to help overcome one of the major problems in lithium‐sulfur batteries.

With the objective of understanding how the mixed convective and the geometrical parameters together influence the nanofluid behavior (enhancement or deterioration) and finding the best configuration of the moving walls for engineering purposes, this paper investigates the single lid-driven mixed convective flow of carbon nanotubes/kerosene nanofluids confined in vertical and horizontal cavities with non-uniform boundary conditions applied to the vertical walls. The findings of this paper can provide crucial conclusions into the behavior and optimization of nanofluids in mixed convective flows in enclosed systems for engineering applications. The system of the governing equations is tackled by a validated in-house code, where we compared the code accuracy with previous experimental and numerical works. The governing parameters are -50 ≤ Pe ≤ 50, 0.5 ≤ A ≤ 4, and 0 ≤ φ ≤ 3%. The effective nanofluid properties are calculated using special experimental models. The outcomes revealed that the carbon nanotube effect on heat transfer depends on the aspect ratio. The greater the aspect ratio, the more pronounced the negative impact of the nanotube concentration where Nusselt number is reduced by 4.49% and 16.17% for φ = 0.01 and 0.03, respectively, in the case of Pe = 0 and A = 4. The Peclet number also has a significant impact on the heat transfer, especially for higher aspect ratios, and diminishes the critical aspect ratio where the nanofluid's behavior changes. An augmentation in the aspect ratio and Peclet number brings about an augmentation in the Nusselt number. Additionally, the Peclet number can reverse the conjugated effect of carbon nanotube volume fraction and aspect ratio on nanofluid enhancement. When Pe = 50 in C1, heat transfer rate is 1.75% and 1.11% enhanced for φ = 0.01 and 0.03, respectively, and A = 4. Moving horizontal walls exhibits higher heat transfer enhancement compared to vertical ones.