Three-dimensional sedimentation patterns of two interacting disks in a viscous fluid

The sedimentation of two spherical solid objects in a viscous fluid has been extensively investigated and well understood. However, a pair of flat disks (in three dimensions) settling in the fluid shows more complex hydrodynamic behaviors. The present work aims to improve understanding of this phenomenon by performing Direct Numerical Simulations (DNS) and physical experiments. The present results show that the sedimentation processes are significantly influenced by disk shape, characterized by a dimensionless moment of inertia I*, and Reynolds number of the leading disk Re. For the flatter disks with smaller I*, steady falling with enduring contact transits to periodic swinging with intermittent contacts as Re increases. The disks with larger I* tend to fall in a Drafting-Kissing-Tumbling (DKT) mode at low Re and to remain separated at high Re. Based on I* and Re, a phase diagram is created to classify the two-disk falling into ten distinctive patterns. The planar motion or three-dimensional motion of the disks is determined primarily by Re. Turbulent disturbance flows at a high Re contribute to the chaotic three-dimensional rotation of the disks. The chance for the two disks to contact is increased when I* and Re are reduced.Comment: 51 pages, 28 figure

Cdc42 is essential for the polarized movement and adhesion of human dental pulp stem cells

Objective: Stem cell-based tissue repair and regeneration require the regulation of cell migration and adhesion. As a regulator of cell polarization, Cdc42 (cell division control protein 42) plays a basic role at the initial stage of cell migration and adhesion. This study explores the effect of Cdc42 on the polarized migration and adhesion of hDPSCs (human dental pulp stem cells). Design: HDPSCs were isolated from extracted third molars and transfected with siRNA targeted against Cdc42. Scratch wound assays and transwell assays were performed to detect the migration of human dental pulp stem cells. Polarization assays were applied to explore the polarized movement of Golgi bodies and nuclei. Western blot was used to examine the expression of related proteins. Results: The expression of Cdc42 was knocked down by siRNA transfection, which inhibited the migration of hDPSCs in both the scratch wound assays and transwell assays. Meanwhile, the proportion of polarized hDPSCs during migration was also decreased, and the adhesion ability of hDPSCs was downregulated. Western blot demonstrated that these effects were dependent on FAK (focal adhesion kinase), β-catenin and GSK3β (Glycogen synthase kinase-3β). Conclusion Our study demonstrates that Cdc42 plays an essential role during the polarized movement and adhesion of hDPSCs

Preparation and properties of antistatic high-strength aramid III/MWCNTs-OH fibers

Composite fibers made from aramid III and hydroxylated multiwalled carbon nanotubes (MWCNTs-OH) combine the excellent mechanical and electrical properties of both components, resulting in strong antistatic performance. However, it is of paramount importance to ensure the homogeneous dispersion of multi-walled carbon nanotubes functionalized with hydroxyl groups (MWCNTs-OH) within the aramid III spinning solution and optimize the compatibility between the two constituents to augment the overall performance of the composite fibers. To this end, this investigation successfully accomplished the dispersion of MWCNTs-OH in the spinning solution and probed the dispersion mechanism using molecular dynamics simulations. Moreover, composite fibers, comprising 2.4 weight percent MWCNTs-OH, were initially fabricated using the wet spinning method. These fibers displayed a uniform texture and a tensile strength of 1.210 GPa, signifying a noteworthy enhancement of 113.25% in comparison to the strength prior to modification. With respect to thermal behavior, the fibers exhibited a mass reduction of 21.24% within the temperature range of 0°C–538°C. In the temperature interval from 538°C to 800°C, the mass loss diminished to 10.31%, representing a substantial 71.03% reduction when compared to the unmodified state. Remarkably, even when subjected to temperatures exceeding 800°C, the composite fibers retained a residual mass of 68.45%, indicating a notable 61.17% increase from their initial condition. In terms of electrical properties, the fibers exhibited a specific resistance (ρ) of 3.330 × 109 Ω cm, demonstrating effective antistatic behavior. In summary, the antistatic composite fibers studied in this paper can effectively mitigate the hazards of static electricity in various applications, including military protection and engineering equipment in both military and civilian fields

The effect of cold stress on the root-specific lipidome of two wheat varieties with contrasting cold tolerance

Complex glycerolipidome analysis of wheat upon low temperature stress has been reported for above-ground tissues only. There are no reports on the effects of cold stress on the root lipidome nor on tissue-specific responses of cold stress wheat roots. This study aims to investigate the changes of lipid profiles in the different developmental zones of the seedling roots of two wheat varieties with contrasting cold tolerance exposed to chilling and freezing temperatures. We analyzed 273 lipid species derived from 21 lipid classes using a targeted profiling approach based on MS/MS data acquired from schedule parallel reaction monitoring assays. For both the tolerant Young and sensitive Wyalkatchem species, cold stress increased the phosphatidylcholine and phosphatidylethanolamine compositions, but decreased the monohexosyl ceramide compositions in the root zones. We show that the difference between the two varieties with contrasting cold tolerance could be attributed to the change in the individual lipid species, rather than the fluctuation of the whole lipid classes. The outcomes gained from this study may advance our understanding of the mechanisms of wheat adaptation to cold and contribute to wheat breeding for the improvement of cold-tolerance

An AMPKa2-specific phospho-switch controls lysosomal targeting for activation

AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are metabolic kinases that co-ordinate nutrient supply with cell growth. AMPK negatively regulates mTORC1, and mTORC1 reciprocally phosphorylates S345/7 in both AMPK α-isoforms. We report that genetic or torin1-induced loss of α2-S345 phosphorylation relieves suppression of AMPK signaling; however, the regulatory effect does not translate to α1-S347 in HEK293T or MEF cells. Dephosphorylation of α2-S345, but not α1-S347, transiently targets AMPK to lysosomes, a cellular site for activation by LKB1. By mass spectrometry, we find that α2-S345 is basally phosphorylated at 2.5-fold higher stoichiometry than α1-S347 in HEK293T cells and, unlike α1, phosphorylation is partially retained after prolonged mTORC1 inhibition. Loss of α2-S345 phosphorylation in endogenous AMPK fails to sustain growth of MEFs under amino acid starvation conditions. These findings uncover an α2-specific mechanism by which AMPK can be activated at lysosomes in the absence of changes in cellular energy

Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis

AMP-activated protein kinase (AMPK) is a master regulator of cellular energy homeostasis and a therapeutic target for metabolic diseases. Co/post-translational N-myristoylation of glycine-2 (Gly2) of the AMPK β subunit has been suggested to regulate the distribution of the kinase between the cytosol and membranes through a “myristoyl switch” mechanism. However, the relevance of AMPK myristoylation for metabolic signaling in cells and in vivo is unclear. Here, we generated knockin mice with a Gly2-to-alanine point mutation of AMPKβ1 (β1-G2A). We demonstrate that non-myristoylated AMPKβ1 has reduced stability but is associated with increased kinase activity and phosphorylation of the Thr172 activation site in the AMPK α subunit. Using proximity ligation assays, we show that loss of β1 myristoylation impedes colocalization of the phosphatase PPM1A/B with AMPK in cells. Mice carrying the β1-G2A mutation have improved metabolic health with reduced adiposity, hepatic lipid accumulation, and insulin resistance under conditions of high-fat diet-induced obesity

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator

The AMP-activated protein kinase (AMPK) αβγ heterotrimer is a primary cellular energy sensor and central regulator of energy homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake and provides an opportunity for new strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2β2γ1 isoform combination as the heterotrimer complex primarily responsible. With the goal of developing α2β2-specific activators, here we perform structure/function analysis of the 2-hydroxybiphenyl group of SC4, an activator with tendency for α2-selectivity that is also capable of potently activating β2 complexes. Substitution of the LHS 2-hydroxyphenyl group with polar-substituted cyclohexene-based probes resulted in two AMPK agonists, MSG010 and MSG011, which did not display α2-selectivity when screened against a panel of AMPK complexes. By radiolabel kinase assay, MSG010 and MSG011 activated α2β2γ1 AMPK with one order of magnitude greater potency than the pan AMPK activator MK-8722. A crystal structure of MSG011 complexed to AMPK α2β1γ1 revealed a similar binding mode to SC4 and the potential importance of an interaction between the SC4 2-hydroxyl group and α2-Lys31 for directing α2-selectivity. MSG011 induced robust AMPK signalling in mouse primary hepatocytes and commonly used cell lines, and in most cases this occurred in the absence of changes in phosphorylation of the kinase activation loop residue α-Thr172, a classical marker of AMP-induced AMPK activity. These findings will guide future design of α2β2-selective AMPK activators, that we hypothesise may avoid off-target complications associated with indiscriminate activation of AMPK throughout the body

Discovery of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Todarodes pacificus and Their Inhibitory Mechanism: In Silico and In Vitro Studies

In order to rapidly and efficiently excavate antihypertensive ingredients in Todarodes pacificus, its myosin heavy chain was hydrolyzed in silico and the angiotensin-converting enzyme (ACE) inhibitory peptides were predicted using integrated bioinformatics tools. The results showed the degree of hydrolysis (DH) theoretically achieved 56.8% when digested with papain, ficin, and prolyl endopeptidase (PREP), producing 126 ACE inhibitory peptides. By predicting the toxicity, allergenicity, gastrointestinal stability, and intestinal epithelial permeability, 30 peptides were finally screened, of which 21 had been reported and 9 were new. Moreover, the newly discovered peptides were synthesized to evaluate their in vitro ACE inhibition, showing Ile-Ile-Tyr and Asn-Pro-Pro-Lys had strong effects with a pIC50 of 4.58 and 4.41, respectively. Further, their interaction mechanisms and bonding configurations with ACE were explored by molecular simulation. The preferred conformation of Ile-Ile-Tyr and Asn-Pro-Pro-Lys located in ACE were successfully predicted using the appropriate docking parameters. The molecular dynamics (MD) result indicated that they bound tightly to the active site of ACE by means of coordination with Zn(II) and hydrogen bonding and hydrophobic interaction with the residues in the pockets of S1 and S2, resulting in stable complexes. In summary, this work proposed a strategy for screening and identifying antihypertensive peptides from Todarodes pacificus

City branding of Beijing and Shanghai: Brand associations among stakeholders

Tato diplomová práce zkoumala image a asociace značky města, umístění, strategie a hlavní výzvy, kterým čelí manažeři městských značek v Pekingu a Šanghaji. Tento kvalitativní výzkum využíval hloubkové rozhovory ke sběru dat od účastníků. Závěry práce naznačují, že různé zúčastněné strany mohou vytvořit různé asociace značek pro město podle jeho atributů a jeho jedinečných zkušeností nebo potřeb zájmů. Tyto asociace mohou být pozitivní nebo negativní. Zatímco pozitivní asociace městských značek mohou městu přinést významné výhody, negativní asociace se značkami mohou mít opačný účinek a poškodit pověst města. Tato práce má významné důsledky pro strategie značení města v Šanghaji a Pekingu. Podívejte se prosím na abstrakt v anglické verzi.This thesis explored the city brand image and associations, positioning, strategies, and the main challenges faced by city brand managers in Beijing and Shanghai. This qualitative research used in-depth interviews to collect data from the participants. The thesis findings indicated that different stakeholders may establish different brand associations for a city according to its attributes and its unique experience or interest needs. These associations can be positive or negative. While positive city brand associations can bring significant benefits to a city, negative brand associations may have the opposite effect and damage a city's reputation. This thesis has significant implications for the city branding strategies of Shanghai and Beijing and provides insights for city brand practitioners and policy makers, highlighting the key role of stakeholders in building and maintaining successful city brands