Polarization Changes Research Articles

APOE expression in papillary thyroid carcinoma: Influencing tumor progression and macrophage polarization

BackgroundAs metastatic papillary thyroid carcinoma becomes increasingly challenging to treat, immunotherapy has emerged as a new research direction. Tumor-associated macrophages (TAMs) influence the occurrence, invasion, and metastasis of tumors. Apolipoprotein E (APOE) can regulate the polarization changes of macrophages and participate in the remodeling of the tumor microenvironment. However, the role of APOE in regulating the polarization and biological functions of TAMs in papillary thyroid carcinoma (PTC) remains unclear, as it acts as a dual biomarker. MethodsWe probed APOE expression in PTC tissues using immunohistochemical staining. A cell co-culture model was established where different APOE-expressing K1 cells were co-cultured with THP-1-derived M0 macrophages. An in-depth analysis of macrophage polarization behavior was performed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Subsequently, the impact of APOE-regulated macrophages on tumor cell behavior, especially proliferation, migration, and invasion, was evaluated utilizing IncuCyte ZOOM system, flow cytometry, colony formation, and scratch experiments. Finally, we used a xenograft model to confirm the effects of APOE on PTC tumorigenesis. ResultsTumor dimensions, stage, and lymphatic metastases were significantly associated with increased APOE expression in PTC tissues. K1 cells were markedly limited in their proliferation, migration, and invasion abilities when APOE expression was silenced, a process mediated by the PI3K/Akt/NF-κB signaling axis. Moreover, APOE is a key facilitator of the enhancement of the anti-inflammatory cytokines IL-10 and TGF-β1. In PTC cellular models, APOE contributed to the phenotypic shift of THP-1 derived macrophages towards an M2 phenotypic polarization, predominantly through the modulation of IL-10. Furthermore, in vivo studies involving athymic nude mice have demonstrated pivotal role of APOE in tumor progression and the induction of M2-like TAM polarization. ConclusionOur results elucidated that APOE could promote the shift of TAMs from M0-type to M2-type polarization by regulating inflammatory factors expressions in K1 cell through the PI3K/Akt/NF-κB pathway. These findings are crucial for understanding the molecular mechanisms underlying PTC pathogenesis and for developing immunological drugs to treat this disease.

Tanshinol ameliorates imiquimod-induced psoriasis by inhibiting M1 macrophage polarization through suppression of the notch signaling pathway

BackgroundPsoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza, which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis.MethodsAn imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway.ResultsThe results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines.ConclusionsCollectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization.

Wavefront rotator with near-zero mean polarization change

A K-mirror is a device that rotates the wavefront of an incident optical field. It has recently gained prominence over the Dove prism, another commonly used wavefront rotator, due to the fact that while a K-mirror has several controls for adjusting the internal reflections, a Dove prism is made of a single glass element with no additional control. Thus, one can obtain much lower angular deviations of transmitting wavefronts using a K-mirror than with a Dove prism. However, the accompanying polarization changes in the transmitted field due to rotation persist even in the commercially available K-mirrors. A recent theoretical work [Appl. Opt. 61, 8302 (2022)APOPAI0003-693510.1364/AO.472543] shows that it is possible to optimize the base angle of a K-mirror for a given refractive index such that the accompanying polarization changes are minimum. In contrast, we show in this paper that by optimizing the refractive index it is possible to design a K-mirror at any given base angle and with any given value for the mean polarization change, including near-zero values. Furthermore, we experimentally demonstrate a K-mirror with an order-of-magnitude lower mean polarization change than that of the commercially available K-mirrors. This can have important practical implications for OAM-based applications that require precise wavefront rotation control.

Molecular ferroelectric with low-magnetic-field magnetoelectricity at room temperature

Magnetoelectric materials, which encompass coupled magnetic and electric polarizabilities within a single phase, hold great promises for magnetic controlled electronic components or electric-field controlled spintronics. However, the realization of ideal magnetoelectric materials remains tough due to the inborn competion between ferroelectricity and magnetism in both levels of symmetry and electronic structure. Herein, we introduce a methodology for constructing single phase paramagnetic ferroelectric molecule [TMCM][FeCl4], which shows low-magnetic-field magnetoelectricity at room temperature. By applying a low magnetic field (≤1 kOe), the halogen Cl‧‧‧Cl distance and the volume of [FeCl4]− anions could be manipulated. This structural change causes a characteristic magnetostriction hysteresis, resulting in a substantial deformation of ~10−4 along the a-axis under an in-plane magnetic field of 2 kOe. The magnetostrictive effect is further qualitatively simulated by density functional theory calculations. Furthermore, this mechanical deformation significantly dampens the ferroelectric polarization by directly influencing the overall dipole configuration. As a result, it induces a remarkable α31 component (~89 mV Oe−1 cm−1) of the magnetoelectric tensor. And the magnetoelectric coupling, characterized by the change of polarization, reaches ~12% under 40 kOe magnetic field. Our results exemplify a design methodology that enables the creation of room-temperature magnetoelectrics by leveraging the potent effects of magnetostriction.

Polarity-Driven Fluorescence Monitoring of Lipid Droplet Dynamics in Dry Eye Disease.

The emergence of lipid droplets (LDs) has been recognized as cellular markers of ocular surface hyperosmosis, which is recognized as a fundamental mechanism driving dry eye disease (DED), while their dynamics during DED progression and therapy remains unlocked. For this purpose, an LD-specific fluorescent probe P1 is presented in this work that exhibits highly selective and sensitive emission enhancement in response to a decreased ambient polarity (Δf) from 0.209 to 0.021. The hydrophobic nature of P1 enables specific staining of LDs, facilitating visualization of changes in polarity within these cellular structures. Utilizing P1, we observe a decrease in polarity accompanied by an increase in the size and number of LDs in hyperosmotic human corneal epithelial cells (HCECs). Furthermore, interplays between LDs and cellular organelles such as mitochondria and the Golgi apparatus are visualized, suggesting the underlying pathogenesis in DED. Notably, the variations of LDs are observed after the inhibition of ferroptosis or activation of autophagy in hyperosmotic HCECs, implying the great potential of LDs as indicators for the design and efficacy evaluation of DED drugs regarding ferroptosis or autophagy as targets. Finally, LDs are confirmed to be overproduced in corneal tissues from DED mice, and the application of clinical eye drops effectively impedes these changes. This detailed exploration underscores the significant roles of LDs as an indicator for the deep insight into DED advancement and therapy.

Raman Spectra of Amino Acids and Peptides from Machine Learning Polarizabilities.

Raman spectroscopy is an important tool in the study of vibrational properties and composition of molecules, peptides, and even proteins. Raman spectra can be simulated based on the change of the electronic polarizability with vibrations, which can nowadays be efficiently obtained via machine learning models trained on first-principles data. However, the transferability of the models trained on small molecules to larger structures is unclear, and direct training on large structures is prohibitively expensive. In this work, we first train two machine learning models to predict the polarizabilities of all 20 amino acids. Both models are carefully benchmarked and compared to density functional theory (DFT) calculations, with the neural network method being found to offer better transferability. By combination of machine learning models with classical force field molecular dynamics, Raman spectra of all amino acids are also obtained and investigated, showing good agreement with experiments. The models are further extended to small peptides. We find that adding structures containing peptide bonds to the training set greatly improves predictions, even for peptides not included in training sets.

Polarity-sensitive fluorescent probe based on coumarin derivatives for imaging lipid droplets and diagnosis of non-alcoholic fatty liver

Aberrant alterations in the polarity of lipid droplets (LDs) are closely linked to disorders of lipid metabolism, which can result in LDs dysfunction and the onset of various diseases, including non-alcoholic fatty liver disease (NAFLD) and specific types of cancer. Therefore, it is imperative to comprehensively comprehend and accurately diagnose associated diseases by monitoring changes in LDs polarity in real time. In this paper, we designed and synthesized four novel fluorescent probes XOT1-XOT4 by using coumarin as a polarity-sensitive group and incorporate various triphenylamine derivatives as electron-donating groups, enabling specific targeting of LDs. All four probes possess high sensitivity towards minute polarity changes. Among them, XOT3 exhibited excellent photophysical properties and demonstrated a linear fluorescence change (R2 = 0.98596) within the polarity range of Δf = 0.023496 ∼ 0.047464. Moreover, probe XOT3 could be effectively utilized for visualizing intracellular LDs by precisely targeting them without requiring any washing steps. Importantly, probe XOT3 has been successfully utilized to monitor alterations in the polarity of LDs during apoptosis and ferroptosis as well as the quantity, size, and fluorescence intensity of LDs stimulated by oleic acid. Furthermore, probe XOT3 was capable of effectively visualizing LDs in tissues and organs in mouse models of non-alcoholic fatty liver disease (NAFLD), which provides a powerful tool for the early diagnosis of NAFLD.

Impact of solvent temperature on graphite shear exfoliation efficiency

Liquid phase exfoliation (LPE) of graphite is a promising pathway for graphene flakes (GF) due to its scalability and cost-effectiveness. However, the method has significant limits at the industrial scale, such as low yield of GF and long processing times. In this study, we investigate the effect of organic solvents such as N-methyl-2-pyrrolidone (NMP) and methyl-5-(dimethylamino)-2-methyl-5-oxopentanoate (PolarClean) temperature on shear-induced exfoliation. The GF concentration was successfully obtained 0.62 mg/ml in NMP and 0.68 mg/ml in PolarClean within just 2 h at 263 K, without surfactants or any additional additives. These results revealed the improved exfoliation efficiency due to changes in solvent polarity, surface tension, and dispersion stability with increased viscosity. In addition, we investigate the optimization conditions required for liter-scale shear-induced exfoliation of graphite in PolarClean. As-prepared GF has significant potential as an effective nanofiller for enhancing the mechanical strength of commercial polymers. This study not only advances the understanding of the LPE mechanisms but also paves the way for the industrial application of this method in the green synthesis of graphene-based nanocomposites.

Congenital FⅦ Deficiency Associated with a Novel Mutation in F7 Gene

To identify the genetic mutation of coagulation factor Ⅶ ( F7) gene in a pedigree with coagulation factor Ⅶ (FⅦ) deficiency and explore the molecular pathogenesis. The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (DD), fibrin degradation products (FDP) and coagulation factor Ⅶ activity (FⅦ:C) of the proband and her family members were detected by Sysmex-CS5100 analyzer. All exons and exon-intron boundaries of the F7 gene were amplified by PCR followed by direct sequencing. The detected mutation was confirmed by reverse sequencing. The ClustalW software was used to analyze the conservatism of the mutant site. Pathogenicity of the mutation was assessed with Mutation Taster and PolyPhen-2 online bioinformatics software. Structure of the mutant protein was analyzed using Swiss-PdbViewer software. The results of routine coagulation tests showed that PT of the proband was markedly extended to 42.5 s, and her FⅦ:C significantly reduced to 2%. The FⅦ:C of her grandmother, mother and sister had slightly reduced to 49%, 51%, and 42%, respectively. These coagulant parameters of her father were within the normal range. Genetic analysis reveled a heterozygous G>A change at cDNA 646 in exon 6 of F7 gene in the proband, resulting in a replacement of glycine at 156 of FⅦ catalytic region with serine (p.Gly156Ser). The sequencing results of other exons and exon-intron boundaries of her F7 gene were normal. The proband's grandmother, mother and sister were all the carriers of this missense mutation except her father. Bioinformatics analysis showed that the p.Gly156Ser mutation caused polarity change of the amino acid at this site and formation of side chains, leading to increase of protein instability, which may affect catalytic activity of structural domain. Meanwhile, both Mutation Taster and PolyPhen-2 online bioinformatics software also predicted the pathogenicity of this missense mutation with high scores. The heterozygous p.Gly156Ser mutation is the direct cause of the reduced FⅦ in this proband.

Deneb Is a Large-amplitude Polarimetric Variable

We write to report the discovery that Deneb is a large-amplitude polarization variable. Over a ∼400 days time span from 2022 August Deneb’s polarization was typically around 3900 parts per million (ppm) in the SDSS g′ band. Yet, it varied by several hundred parts per million in an irregular way on a timescale of weeks. The largest polarization change, amounting to 2500 ppm, occurred shortly after the last pulsation “resumption” event identified by Abt et al. in TESS photometry. The relationship between the observed polarization—particularly corresponding to the resumption event—and its brightness and H α spectra suggests a mechanism involving density changes in its wind and/or extended atmosphere. Smaller effects due to pulsations are not ruled out, and further study is recommended.

Spontaneous and tunable valley polarization in two-dimensional single-layer LaCl2

Applying the valley contrasting properties of valleytronic materials to logical operations is the foundation of valleytronic device manufacturing. It is predicted that single-layer (SL) LaCl2 is an ferrovalley material with intrinsic and tunable valley polarization through first-principles calculations. It is a ferromagnetic semiconductor (bandgap 0.767 eV) with roughly 1.0 μ B per unit cell as well as out of plane magnetization, and the Curie temperature is about 149 K. The tight-binding model considering five orbitals as well as next nearest neighboring hopping get a consistent band structure with the first-principles calculation. The valley polarization changes from 40.49 to 98.51 meV under the biaxial strain of 5% ∼ −5%. Therefore, the biaxial strain can be a means to tune the valley polarization. In addition, the valley polarization of the double-layer (DL) structure (∼80 meV) is much greater than that of the SL structure (∼59 meV) due to the increased magnetic moment of the DL structure, indicating the potential tunable character by stacking few layers. We believe that SL LaCl2 has great potential for device manufacturing and application in the field of valley electronics.

Design of QCA based memory cell using a novel majority voter with physical validation

Quantum Dot Cellular Automata (QCA) is a unique transistor less paradigm which effectively uses change in cell polarization to perform logical operations with high speed, low power and high intricacy. In recent years, the need of high performance memory cell is increased for improving the system performance. This paper presents the design of a QCA based memory cell with read write capabilities. In recent past, most of the QCA circuits are designed using the conventional three input majority voter. The conventional three input majority gate is not fault tolerant. Thus, we need an alternative design which can serve as the majority voter and also shows the fault tolerance. Moreover, the design of three input majority voter is not much addressed . In this paper, an alternative, simple structure of three input majority voter is presented which is better than the conventional one in terms of fault tolerance. In addition to this, the proposed three input majority voter is power aware and efficient to realize various digital circuits. The correctness of the proposed majority voter is validated through the physical proof. Moreover, the proposed gate is subjected to cell displacement defect to investigate the testability. The proposed gate is further used to implement rudimentary elements such as XOR gate, multiplexer and D latch. Finally, the design of Random Access Memory (RAM) cell with read, write, set and reset capabilities is proposed using the presented majority voter. The proposed circuits are further subjected to comprehensive analyses for estimation of cost functions and energy dissipation. The investigation of presented circuits manifests the use of proposed majority voter for next generation computing circuits.

The 11th: Politics, Polarization, and Partisan Change in a Southern District, 1972–2022

Abstract What can be learned from analysis of a single congressional district? This paper uses the experience of North Carolina’s 11th congressional district to understand the political changes that have defined the last half-century in the American South. The story of how this once politically inconsequential southern Appalachian district found itself in the middle of the national political maelstrom is, in many ways, the story of southern politics over the last three decade. Political polarization, strategic gerrymandering, the power of national political tides, the increasing urban/rural divide and the broader partisan transformation of the South that has remade American politics all are reflected in the 11th. In addition to uncovering new wrinkles in the story of southern partisan change, this paper defines and highlights the advantages of place-based Political Science.

Gamma-irradiation-induced tailoring of physical, electrical, optical, and mechanical properties of PVC/PANI/TiO2 nanocomposites for different applications

Gamma irradiation exhibits a complex influence on the properties of PVC/PANI/TiO2 nanocomposite films. XRD analysis reveals a non-monotonic response in crystallinity, with an initial increase at lower doses due to crosslinking followed by a decrease at higher doses attributed to polymer chain scission. Mechanical properties exhibit an improvement in tensile strength and Young's modulus at moderate doses (up to 100 kGy) due to crosslinking. However, excessive irradiation (>100 kGy) induces chain degradation, causing a decrease in both tensile strength and elongation at break. Similar dose-dependent behavior is observed in thermal properties, with moderate doses improving thermal stability and melting temperature before a decline at higher doses due to chain degradation. Gamma irradiation significantly affects AC conductivity, suggesting potential changes in structure, charge carrier density, and conduction mechanisms. While the core chemical structure remains largely unaffected, FTIR and UV–Vis spectroscopy analyses indicate alterations in the degree of crosslinking and optical properties, warranting further investigation. Refractive index increases with irradiation due to enhanced density and changes in polarizability. This study highlights the importance of tailoring the gamma irradiation dose to achieve desired properties in PVC/PANI/TiO2 nanocomposite films for various applications.

Optical evaluation of internal damage to human hair based on second near-infrared window polarization microscopy.

Hair beauty treatments glorify human life. As a side effect, there is a risk of deteriorating the health of the hair. Optically polarized microscopy has been used for many decades to evaluate hair conditions owing to its ease of use and low operating costs. However, the low biopermeability of light hinders the observation of detailed structures inside hair. The aim of this study is to establish an evaluation technique of internal damages in a hair by utilizing a near-infrared (NIR) light with a wavelength of 1000-1600 nm, called "second NIR window". We built a laser scanning transmission microscope system with an indium gallium arsenide detector, a 1064 nm laser source, and optical circular polarization to visualize the anisotropy characterization of keratin fibres in hair. Samples of Asian black hair before and after bleaching, after permanent-waving, after lithium bromide (LiBr) treatment, and after heating was observed. Some parameters reflecting intra-hair damage were quantitatively compared with the parameters in digitally recorded images with analytical developments. The light transmittance of black hair was dramatically improved by utilizing the second NIR window. Numerical analysis of circular polarization in hair quantified the internal damage in chemically or thermally treated hair and found two different types of damage. The present method enabled quantitative evaluation of the condition changes in the cortex; for example, a decrease in circular polarizability by LiBr treatment and restoration by replacing the LiBr solution with water. In addition, black speckles were observed after the heat treatment. Longer heating and wetting times increased the appearance probability and size of the speckles. According to quantitative analyses, the emergence of black spots was independent of polarizability changes, indicating that they were not pores. Circular polarization microscopy based on near-infrared optics in the second NIR window provides an effective evaluation method for quantifying intra-hair damage caused by cosmetic treatments. The present method provides noninvasive, easy, and inexpensive hair evaluation and has potential as a gold standard in hair care research/medical fields.

Fluorescence and Lifetime Imaging of Endoplasmic Reticulum Polarity Change During Ferroptosis.

As a new form of regulated cell death, ferroptosis is closely related to various diseases. Tracing ferroptosis related biological behavior is helpful to better understand this process and its related biology. Considering that ferroptosis is featured with remarkable lipid peroxidation which can easily change the membranes' compositions and structures, it is potential to detect intracellular environmental changes for direct assessment of ferroptosis. In view of the close relationship between endoplasmic reticulum (ER) and ferroptosis, we designed an ER-targeted and polarity-sensitive fluorescent probe SBD-CH, which has superior photostability and can respond to polarity with high selectivity without the affection of viscosity. SBD-CH can monitor the trend of ER polarity during ferroptosis by confocal laser scanning microscopy (CLSM), and analyze the distribution of polarity in ferroptosis by fluorescence lifetime imaging microscopy (FLIM). During Erastin induced ferroptosis, the polarity of ER in HT-1080 cells increased and the polarity distribution in ER was more dispersed. Our work provides an effective strategy for evaluating the process of ferroptosis by monitoring the changes of ER polarity.

Use of GIS tools, enhanced by FFT filtering methods, to detect blurred craters in Synthetic Digital Elevation Models, to improve their location and morphological characterisation

Filtered Geomorphic Reference Models (FGRMs), extracted from High-Pass Filters based on the Fast Fourier Transform (HPF-FFT), provide a semi-automated and objective detection of a wide range of geoforms and geomorphic situations (flat areas, slopes, depressions, or valley bottoms). The method is sensitive enough to reveal numerous inflection points that enable the identification of subtle changes in relief polarity, resulting in accurate representations of real land depressions. The effectiveness of this method has been demonstrated in lunar landscapes, utilizing altimetry extracted from high-precision Planetary Digital Elevation Models (PDEMs) to construct crater inventories with well-defined FGRMs. However, when analysing lunar environments with closely-spaced geomorphic features, the FGRMs display blurring and generalization effects, reducing their capability to identify all existing crater depressions. This limitation controls the ability of FGRMs, to generate reliable crater inventories. This study examines such effects in three experiments. Using Synthetic Digital Relief Models (SDRMs) constructed by means of a MATLAB script two experiments are performed. In Experiment_1 different scenarios of proximity between aligned craters are analysed. The marks, or footprints, formed by craters of identical size and shape (i.e., circular bowl-shaped depressions with central peaks) are considered, resulting in simplified PDEMs. Various scenarios of crater centre separation (proximity) and the presence of internal features within craters are also analysed. Experiment_2 validates the method with different proximities, locations and crater sizes. Experiment_3 validates the approach in a sampled area of LRO lunar PDEM corresponding to Zelinskiy crater (Mare Ingenii area). To address these blurring effects, a hybrid methodology is employed, generating FGRMs extracted from HPF-FFT, in conjunction with other GIS and remote sensing tools, such as singular point zoning, aspect-slope zoning, and edge-limits zoning. As a result, the correspondence between the FGRMs and the synthetic forms is examined, aiding the comprehension of the graphical response provided by filtering in these cratered areas. The methodology demonstrates that FGRMs derived from HPF-FFT are sensitive to capturing connections between shapes as soon as the crater features start to merge, while blurring becomes evident when the craters are located at a proximity of <20 model units. Additionally, the results highlight the method's utility in accurately locating crater footprints and morphologically characterizing inner crater features, even when crater centres are closely spaced. This approach effectively mitigates blurring effects and enables the precise localization of crater marks and their internal features. The validations carried out in complex relief and high precise DEMs provide a use in real situation.

Refractive Index and Dispersion Measurement Principle with Polarization Change in Total Internal Reflection

Refractive Index and Dispersion Measurement Principle with Polarization Change in Total Internal Reflection

Challenges and opportunities in piezoelectric polymers: Effect of oriented amorphous fraction in ferroelectric semicrystalline polymers

AbstractDespite extensive research on piezoelectric polymers since the discovery of piezoelectric poly(vinylidene fluoride) (PVDF) in 1969, the fundamental physics of polymer piezoelectricity has remained elusive. Based on the classic principle of piezoelectricity, polymer piezoelectricity should originate from the polar crystalline phase. Surprisingly, the crystal contribution to the piezoelectric strain coefficient d31 is determined to be less than 10%, primarily owing to the difficulty in changing the molecular bond lengths and bond angles. Instead, &gt;85% contribution is from Poisson's ratio, which is closely related to the oriented amorphous fraction (OAF) in uniaxially stretched films of semicrystalline ferroelectric (FE) polymers. In this perspective, the semicrystalline structure–piezoelectric property relationship is revealed using PVDF‐based FE polymers as a model system. In melt‐processed FE polymers, the OAF is often present and links the crystalline lamellae to the isotropic amorphous fraction. Molecular dynamics simulations demonstrate that the electrostrictive conformation transformation of the OAF chains induces a polarization change upon the application of either a stress (the direct piezoelectric effect) or an electric field (the converse piezoelectric effect). Meanwhile, relaxor‐like secondary crystals in OAF (SCOAF), which are favored to grow in the extended‐chain crystal (ECC) structure, can further enhance the piezoelectricity. However, the ECC structure is difficult to achieve in PVDF homopolymers without high‐pressure crystallization. We have discovered that high‐power ultrasonication can effectively induce SCOAF in PVDF homopolymers to improve its piezoelectric performance. Finally, we envision that the electrostrictive OAF mechanism should also be applicable for other FE polymers such as odd‐numbered nylons and piezoelectric biopolymers.

#2834 Analysis of cyst hetero- and homogeneity to unravel common pathways in autosomal dominant polycystic kidney disease

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, with a prevalence of 1 in ca. 1000 individuals and accounting for 10% of the European dialysis population. It is most frequently (75-80%) caused by mutations in the PKD1 gene encoding Polycystin-1. Besides systemic manifestations such as liver cysts, hypertension and cardiac abnormalities, the most prominent phenotype is the gradual development of kidney cysts, leading to kidney enlargement and a decline in kidney function leading to end-stage kidney disease at an average age of ca. 50 years. The cysts arise from tubular epithelial cells in the nephron that start to dedifferentiate, proliferate and eventually secrete fluid into the cyst lumen promoting its swelling. This process is molecularly regulated by changes in Ca2+, cAMP, PKA and PI3K-Akt-mTOR signaling, among others. The renal cysts are further characterized by ciliary dysfunction, altered signal transduction, loss of polarity, apoptosis, mitochondrial abnormalities, metabolic reprogramming, inflammation, oxidative stress and epigenetic changes. However, the exact sequence of events and their relative importance in the process of cyst formation remains unclear. Therefore, we analyzed the transcriptomic cyst hetero- and homogeneity to identify the pathways that were different, but also shared among individual cysts. Method We performed RNA-Seq analysis on 40 individual cystic membranes of nephrectomized kidneys of 4 PKD1 patients. We included 4 samples of macroscopically healthy tissue from 2 ADPKD kidneys (histologically confirmed to have microcysts) and 4 samples from 4 healthy kidneys. Principal component, cluster and trajectory analysis was performed to explore cyst heterogeneity. Adjacent pieces of cystic membrane were analyzed for histology (H&amp;E, Sirius Red) or stained with FITC-tagged Lotus Tetragonolobus Lectin (LTL) or Dolichos Biflorus Agglutinin (DBA), a proximal and distal tubular marker, respectively. Results Although the cysts clearly separated from the healthy tissues in the analyses, there was also a distinct heterogeneity observed among the cysts that was independent of patient, gender, cyst size, location or fluid color. Pathway analysis revealed that these changes were characterized by a gradual increase of interstitial (remodeling) and inflammation markers, and a gradual decrease in differentiation markers (e.g. development, intercellular junctions, basement membrane) along the trajectory pseudotime. We could identify 6 clusters of cystic samples, with 2 clusters deviating from the main trajectory. With respect to tubular/epithelial dedifferentiation, the decrease in proximal tubular markers already occurred in microcystic tissue and was stronger compared to the other tubular segments. Consequently, none of the analyzed cystic membranes stained positive for LTL, while others showed clear staining for DBA. Microcysts on the other hand stained positive for LTL or DBA. Several cysts showed RNA marker expression of multiple tubular segments. Indeed, smaller macrocysts (diameter in the mm range) were lined by both LTL- and DBA-positive regions. Conclusion By analyzing transcriptomic hetero- and homogeneity among individual cysts, the molecular alterations in ADPKD progression can be tracked down and determined whether they occur similarly in all cysts or at different levels. Our data also suggest that loss of proximal tubular markers in macrocysts is more prominent compared to the decrease in distal markers. Finally, inner cyst walls can consist of cyst-lining cells of multiple origins.