Cytoplasmic SIRT1 promotes paclitaxel resistance in ovarian carcinoma through increased formation and survival of polyploid giant cancer cells.

Therapeutic resistance is a notable cause of death in patients with ovarian carcinoma. Polyploid giant cancer cells (PGCCs), commonly arising in tumor tissues following chemotherapy, have recently been considered to contribute to drug resistance. As a type III deacetylase, Sirtuin1 (SIRT1) plays essential roles in the cell cycle, cellular senescence, and drug resistance. Accumulating evidence has suggested that alteration in its subcellular localization via nucleocytoplasmic shuttling is a critical process influencing the functions of SIRT1. However, the roles of SIRT1 subcellular localization in PGCC formation and subsequent senescence escape remain unclear. In this study, we compared the differences in the polyploid cell population and senescence state of PGCCs following paclitaxel treatment between tumor cells overexpressing wild-type SIRT1 (WT SIRT1) and those expressing nuclear localization sequence (NLS)-mutated SIRT1 (SIRT1NLSmt ). We investigated the involvement of cytoplasmic SIRT1 in biological processes and signaling pathways, including the cell cycle and cellular senescence, in ovarian carcinoma cells' response to paclitaxel treatment. We found that the SIRT1NLSmt tumor cell population contained more polyploid cells and fewer senescent PGCCs than the SIRT1-overexpressing tumor cell population. Comparative proteomic analyses using co-immunoprecipitation (Co-IP) combined with liquid chromatography-mass spectrometry (LC-MS)/MS showed the differences in the differentially expressed proteins related to PGCC formation, cell growth, and death, including CDK1 and CDK2, between SIRT1NLSmt and SIRT1 cells or PGCCs. Our results suggested that ovarian carcinoma cells utilize polyploidy formation as a survival mechanism during exposure to paclitaxel-based treatment via the effect of cytoplasmic SIRT1 on PGCC formation and survival, thereby boosting paclitaxel resistance. © 2023 The Pathological Society of Great Britain and Ireland.

A Dual-Band Polarization-Insensitive Frequency Selective Surface for Electromagnetic Shielding Applications.

This paper presents a novel polarization-insensitive dual-band frequency-selective surface (FSS)-based electromagnetic shield. The miniaturized FSS unit cell consists of a modified Jerusalem crossed loop and a corner-modified square loop. These FSS elements are arranged in a co-planner configuration over a single-layer Rogers 5880 substrate and simultaneously offer effective shielding in the X- and Ku-bands. Moreover, the FSS manifests polarization-independent and angularly stable band-reject filter characteristics over various oblique angles of incidence for both the TE and TM polarizations with virtuous attenuation at both resonances. In addition, the FSS structure is modelled into an equivalent lumped circuit to better analyze the phenomenon of EM wave suppression. A finite prototype of FSS is fabricated and tested. The simulated and measured results are in good agreement, thus making it a potential candidate for RF shielding/isolation applications.

Detecting cylindrical vector beams with an on-chip plasmonic spin-Hall metalens.

In recent years, singular optical beams, including optical vortex (OV) beams with phase singularities and cylindrical vector beams (CVBs) with polarization singularities, have brought new degrees of freedom for many applications. Although there have been various microscale devices for OV detection, the detection of CVBs with a microscale device is still a challenge. Here, we propose a new method for detection of CVBs with a designed on-chip plasmonic spin-Hall metalens structure. The focal position of the metalens and the splitting effect of at focus are studied in both an analytical model and numerical simulation. The results demonstrate that the metalens can not only detect different polarization orders of incident CVBs but also have an ability to distinguish radial, azimuthal and other vectorial polarization states under the same order of CVBs. This method has potential applications in compact integrated optical communication and processing systems.

Experimental demonstration of a time-domain digital-coding metasurface for a Doppler cloak.

By generating an artificial Doppler shift, a Doppler cloak can compensate for the Doppler shift from a moving object. An object covered by a Doppler cloak will be detected as a static object, even if it is actually moving. Herein, we experimentally demonstrate the Doppler cloak in a radar system using a time-domain digital-coding metasurface. We theoretically illustrate an active metasurface with a modulated reflection phase that can imitate the motion of moving, thereby generating an artificial Doppler shift for a Doppler cloak. Moreover, a reflective metasurface composed of voltage-controlled varactor diodes with a 3-bit reflection phase was designed and fabricated. Finally, we experimentally demonstrate that an artificial Doppler shift for a Doppler cloak is obtained from the proposed metasurface using a discrete time-varying bias voltage. Simulation and measurement results show that the proposed time-domain digital-coding metasurface can cancel the Doppler shift and serve as a Doppler cloak. The proposed metasurface may have potential applications in a Doppler radar illusion, Doppler cancellation in vehicle-to-vehicle communications, and wireless communications.

Design and experimental demonstration of Doppler cloak from spatiotemporally modulated metamaterials based on rotational Doppler effect.

Recently, spatiotemporally modulated metamaterial has been theoretically demonstrated for the design of Doppler cloak, a technique used to cloak the motion of moving objects from the observer by compensating for the Doppler shift. Linear Doppler effect has an angular counterpart, i.e., the rotational Doppler effect, which can be observed by the orbital angular momentum (OAM) of light scattered from a spinning object. In this work, we predict that the spatiotemporally modulated metamaterial has its angular equivalent phenomenon. We therefore propose a technique to observe the rotational Doppler effect by cylindrical spatiotemporally modulated metamaterial. Conversely, such a metamaterial is able to cloak the Doppler shift associated with linear motion by generating an opposite rotational Doppler shift. This novel concept is theoretically analyzed, and a conceptual design by spatiotemporally modulating the permittivity of a voltage-controlled OAM ferroelectric reflector is demonstrated by theoretical calculation and numerical simulation. Finally, a Doppler cloak is experimentally demonstrated by a spinning OAM metasurface in radar system, which the spatiotemporal reflection phase are mechanically modulated. Our work presented in this paper may pave the way for new directions of OAM carrying beams and science of cloaking, and also explore the potential applications of tunable materials and metasurfaces.

Rashba Effect and Spin-Dependent Excitonic Properties in Chiral Two-Dimensional/Three-Dimensional Composite Perovskite Films.

Among various chiral semiconductor materials, chiral two-dimensional (2D)/three-dimensional (3D) composite perovskites (CPs) offer the benefits of strong interface asymmetry and energy transfer between 2D and 3D phases, making the chiral CPs promising for spintronic devices. Therefore, understanding their spintronic properties will be greatly important for expanding their relevant applications. In this work, we synthesized one pair of chiral 2D/3D CP films. Their Rashba effect and spin relaxation process have been investigated by polarization-dependent femtosecond transient absorption spectroscopy. Interestingly, under left- and right-handed circularly polarized light (CPL) excitation, a two-photon emission intensity difference is observed in chiral 2D/3D CP films at 298 K. This work sheds light on the spin-dependent excitonic characteristics of chiral 2D/3D CPs and confirms the feasibility of their application in near-infrared CPL detection.

Exogenous plant growth regulator and foliar fertilizers for phytoextraction of cadmium with Boehmeria nivea [L.] Gaudich from contaminated field soil.

As a enrichment plant, ramie can be used for the phytoremediation of cadmium (Cd)-contaminated soil. However, it is worth exploring the role of plant growth regulators and foliar fertilizers in the process of plant growth and development and Cd adsorption. By measuring the agronomic traits, Cd content of aboveground and underground ramie, calculating the Cd transfer coefficient (TF) and Cd bioconcentration factors (BCF), and the correlation between various indicators. This study examined the effects of plant growth regulators and foliar fertilizers on ramie's capacity for Cd accumulation and transportation. Plant growth regulators and foliar fertilizers increased the Cd content of the aboveground ramie, reduced the Cd content of the underground ramie, and increased the TF. Among them, GA-1 increased the Cd content of the aboveground ramie to 3 times more than that of the control and reduced the Cd content of the underground ramie by 54.76%. Salicylic acid (SA) increased the Cd content of the aboveground ramie to three times more than that of the control. The combination of GA and foliar fertilizer reduced the Cd content of the aboveground and underground ramie and the TF and BCF of the underground ramie. After the hormones were sprayed, the TF of ramie had a significant positive correlation with the Cd content of the aboveground ramie; the BCF of the aboveground ramie had a significant positive correlation with the Cd content and TF of the aboveground ramie. The results indicate that Brassinolide (BR), gibberellin (GA), ethephon (ETH), polyamines (PAs), and salicylic acid (SA) have different effects on the enrichment and transport of Cd in ramie. This study provided an effective method to improve the capacity for ramie to adsorb heavy metals during cultivation.

The Diagnostic Value of Serum GDF15 and hs-CTnT in Elderly Patients with Acute Myocardial Infarction.

Objective: To analyze the diagnostic value of serum growth differentiation factor 15 (GDFl5) and high-sensitivity troponin T (hs-cTnT) in elderly acute myocardial infarction (AMI). Methods: A retrospective analysis of 165 patients with acute chest pain admitted to the Department of Cardiology in our hospital from January to December 2020, Among them, 76 AMI patients (AMI group), 89 non-AMI patients (non-AMI group), and 80 healthy people were selected as the control group during the same period. Compare the three groups of serum GDF15, hs-CTnT levels, and left ventricular ejection fraction (LVEF) parallel correlation analysis, and draw the receiver operating curve (ROC) of serum GDF15 and hs-CTnT levels to diagnose AMI. Results: The serum GDF15 and hs-CTnT levels of the AMI group were significantly higher than those of the non-AMI group and the control group, and the difference was statistically significant (p < 0.01). The LVEF was significantly lower than the non-AMI group and the control group, whose difference was statistically significant (p < 0.01). Among them, the indicators of the non-AMI group were both higher and lower than the control group, and the difference was statistically significant (p < 0.01). Serum GDF15 and hs-CTnT levels of AMI patients increased with the increase of NYHA grade, among which grade IV group was significantly higher than grade I∼II group and grade III group (P < 0.01), and grade III group was significantly higher than grade I∼II Group (p < 0.01). Pearson correlation analysis showed that GDF15 and hs-CTnT levels of AMI patients were significantly negatively correlated with LVEF (r = -0.584, -0.612, - < 0.01). The ROC curve showed that GDF15 had a high specificity (93.75%) and hs-CTnT has a high sensitivity (90.67%). The area under the curve for diagnosing AMI is > 0.7 (0.895, 0.948). The sensitivity of the combined detection and the specificity are higher than that of individual detection. Conclusion: Serum GDF15 and hs-CTnT are highly expressed in elderly patients with AMI. The combined detection of the two can improve the efficiency of AMI diagnosis. GDF15 can be used as a new biomarker for AMI diagnosis and disease monitoring.

Recent Progress in Reconfigurable and Intelligent Metasurfaces: A Comprehensive Review of Tuning Mechanisms, Hardware Designs, and Applications.

Intelligent metasurfaces have gained significant importance in recent years due to their ability to dynamically manipulate electromagnetic (EM) waves. Their multifunctional characteristics, realized by incorporating active elements into the metasurface designs, have huge potential in numerous novel devices and exciting applications. In this article, recent progress in the field of intelligent metasurfaces are reviewed, focusing particularly on tuning mechanisms, hardware designs, and applications. Reconfigurable and programmable metasurfaces, classified as space gradient, time modulated, and space-time modulated metasurfaces, are discussed. Then, reconfigurable intelligent surfaces (RISs) that can alter their wireless environments, and are considered as a promising technology for sixth-generation communication networks, are explored. Next, the recent progress made in simultaneously transmitting and reflecting reconfigurable intelligent surfaces (STAR-RISs) that can achieve full-space EM wave control are summarized. Finally, the perspective on the challenges and future directions of intelligent metasurfaces are presented.

AMD-GAN: Attention encoder and multi-branch structure based generative adversarial networks for fundus disease detection from scanning laser ophthalmoscopy images.

The scanning laser ophthalmoscopy (SLO) has become an important tool for the determination of peripheral retinal pathology, in recent years. However, the collected SLO images are easily interfered by the eyelash and frame of the devices, which heavily affect the key feature extraction of the images. To address this, we propose a generative adversarial network called AMD-GAN based on the attention encoder (AE) and multi-branch (MB) structure for fundus disease detection from SLO images. Specifically, the designed generator consists of two parts: the AE and generation flow network, where the real SLO images are encoded by the AE module to extract features and the generation flow network to handle the random Gaussian noise by a series of residual block with up-sampling (RU) operations to generate fake images with the same size as the real ones, where the AE is also used to mine features for generator. For discriminator, a ResNet network using MB is devised by copying the stage 3 and stage 4 structures of the ResNet-34 model to extract deep features. Furthermore, the depth-wise asymmetric dilated convolution is leveraged to extract local high-level contextual features and accelerate the training process. Besides, the last layer of discriminator is modified to build the classifier to detect the diseased and normal SLO images. In addition, the prior knowledge of experts is utilized to improve the detection results. Experimental results on the two local SLO datasets demonstrate that our proposed method is promising in detecting the diseased and normal SLO images with the experts labeling.

Spoof Surface Plasmon Polaritons Power Divider with large Isolation.

Periodic corrugated metal structure is designed to support and propagate spoof surface plasmon polaritons (SSPPs) wave in the microwave frequencies. In this paper, firstly a plasmonic waveguide consisting of oval-ring shaped cells is proposed with the performance of high transmission efficiency in a wide frequency range. The coplanar waveguides (CPWs) with 50 Ω impedance are adopted to feed the energies or extract signals at both ends of the plasmonic waveguide. Then a well-isolated power divider is constructed based on the SSPPs waveguides aiming to equally split the energy of the SSPPs wave into two equal parts. The stepped-impedances are co-designed with the three input/output ports of the power divider to achieve the impedance-matching between the SSPPs waveguides and the coplanar waveguides. Besides, a single resistor is placed in the middle of two symmetrical half oval-rings to realize the isolation between the two output ports over the spectrum of 4.5-7.5 GHz. Finally, both plasmonic waveguide and the power divider are fabricated and tested to verify the predicted characteristics.

3beta -hydroxypregnane steroids are pregnenolone sulfate-like GABA(A) receptor antagonists.

Endogenous neurosteroids have rapid actions on ion channels, particularly GABA(A) receptors, which are potentiated by nanomolar concentrations of 3alpha-hydroxypregnane neurosteroids. Previous evidence suggests that 3beta-hydroxypregnane steroids may competitively antagonize potentiation induced by their 3alpha diastereomers. Because of the potential importance of antagonists as experimental and clinical tools, we characterized the functional effect of 3beta-hydroxysteroids. Although 3beta-hydroxysteroids reduced the potentiation induced by 3alpha-hydroxysteroids, 3beta-hydroxysteroids acted noncompetitively with respect to potentiating steroids and inhibited the largest degrees of potentiation most effectively. Potentiation by high concentrations of barbiturates was also reduced by 3beta-hydroxysteroids. 3beta-Hydroxysteroids are also direct, noncompetitive GABA(A) receptor antagonists. 3beta-Hydroxysteroids coapplied with GABA significantly inhibited responses to > or =15 microm GABA. The profile of block was similar to that exhibited by sulfated steroids, known blockers of GABA(A) receptors. This direct, noncompetitive effect of 3beta-hydroxysteroids was sufficient to account for the apparent antagonism of potentiating steroids. Mutated receptors exhibiting decreased sensitivity to sulfated steroid block were insensitive to both the direct effects of 3beta-hydroxysteroids on GABA(A) responses and the reduction of potentiating steroid effects. At concentrations that had little effect on GABAergic synaptic currents, 3beta-hydroxysteroids and low concentrations of sulfated steroids significantly reversed the potentiation of synaptic currents induced by 3alpha-hydroxysteroids. We conclude that 3beta-hydroxypregnane steroids are not direct antagonists of potentiating steroids but rather are noncompetitive, likely state-dependent, blockers of GABA(A) receptors. Nevertheless, these steroids may be useful functional blockers of potentiating steroids when used at concentrations that do not affect baseline neurotransmission.

Contribution of presynaptic Na(+) channel inactivation to paired-pulse synaptic depression in cultured hippocampal neurons.

Paired-pulse depression (PPD) of synaptic transmission is important for neuronal information processing. Historically, depletion of the readily releasable pool of synaptic vesicles has been proposed as the major component of PPD. Recent results suggest, however, that other mechanisms may be involved in PPD, including inactivation of presynaptic voltage-dependent sodium channels (NaChs), which may influence coupling of action potentials to transmitter release. In hippocampal cultures, we have examined the potential role and relative contribution of presynaptic NaCh inactivation in excitatory postsynaptic current (EPSC) PPD. Based on current- and voltage-clamp recordings from somas, our data suggest that NaCh inactivation could potentially participate in PPD. Paired stimulation of somatic action potentials (20- to 100-ms interval) results in subtle changes in action potential shape that are mimicked by low concentrations of tetrodotoxin (TTX) and that appear to be generated by a combination of fast and slow recovery from NaCh inactivation. Dilute concentrations of TTX dramatically depress glutamate release. However, we find evidence for only minimal contribution of NaCh inactivation to EPSC PPD under basal conditions. Hyperpolarization of presynaptic elements to speed recovery from inactivation or increasing the driving force on Na(+) ions through active NaChs had minimal effects on PPD while more robustly reversing the effects of pharmacological NaCh blockade. On the other hand, slight depolarization of the presynaptic membrane potential, by elevating extracellular [K(+)](o), significantly increased PPD and frequency-dependent depression of EPSCs during short trains of action potentials. The results suggest that NaCh inactivation is poised to modulate EPSC amplitude with small tonic depolarizations that likely occur with physiological or pathophysiological activity.

Activation-dependent properties of pregnenolone sulfate inhibition of GABAA receptor-mediated current.

Sulfated steroids like pregnenolone sulfate (PS) are found endogenously in the central nervous system where they may modulate GABAA receptors. Understanding the mechanism of steroid inhibition is important for understanding the conditions under which endogenous steroids modulate GABAA receptor function, assessing their potential clinical utility, and for evaluating sulfated steroids as probes of receptor behaviour. Some previous studies suggest that sulfated steroid inhibition exhibits activation dependence, whilst other studies suggest only slow, time-dependent inhibition, perhaps reflecting slow PS association with receptors. We tested activation dependence in several ways. Steroid potency increased 2- to 3-fold with approximately 10-fold change in GABA concentration. PS inhibition of saturating partial agonist responses suggested that the level of channel activation, rather than receptor occupancy by agonist, is important for PS inhibition. Inhibition by sulfated steroids exhibited weak or no voltage dependence. Responses to rapid applications of exogenous GABA differed little whether PS was pre-applied or simply co-applied with GABA, consistent with the hypothesis that the actions of PS are facilitated by receptor activation. PS applied during steady-state GABA responses exhibited slow onset and offset rate constants. The offset, rather than onset, was significantly slowed by elevated GABA concentration. At hippocampal synapses, large, multiquantal IPSCs were inhibited more effectively by a fixed concentration of PS than small quantal content IPSCs, consistent with known 'pooling' of transmitter following multiquantal release. Picrotoxinin, although superficially similar to PS in its activation dependence, was dissimilar from PS in a number of details. In summary, PS inhibition exhibits activation dependence that may be explained by activation-dependent binding and altered desensitization.

Selective antagonism of 5alpha-reduced neurosteroid effects at GABA(A) receptors.

Although neurosteroids have rapid effects on GABA(A) receptors, study of steroid actions at GABA receptors has been hampered by a lack of pharmacological antagonists. In this study, we report the synthesis and characterization of a steroid analog, (3alpha,5alpha)-17-phenylandrost-16-en-3-ol (17PA), that selectively antagonized neurosteroid potentiation of GABA responses. We examined 17PA using the alpha1beta2gamma2 subunit combination expressed in Xenopus laevis oocytes. 17PA had little or no effect on baseline GABA responses but antagonized both the response augmentation and the direct gating of GABA receptors by 5alpha-reduced potentiating steroids. The effect was selective for 5alpha-reduced potentiating steroids; 5beta-reduced potentiators were only weakly affected. Likewise, 17PA did not affect barbiturate and benzodiazepine potentiation. 17PA acted primarily by shifting the concentration response for steroid potentiation to the right, suggesting the possibility of a competitive component to the antagonism. 17PA also antagonized 5alpha-reduced steroid potentiation and gating in hippocampal neurons and inhibited anesthetic actions in X. laevis tadpoles. Analogous to benzodiazepine site antagonists, the development of neurosteroid antagonists may help clarify the role of GABA-potentiating neurosteroids in health and disease.

Neuroactive steroid interactions with voltage-dependent anion channels: lack of relationship to GABA(A) receptor modulation and anesthesia.

Neuroactive steroids modulate the function of gamma-aminobutyric acid type A (GABA(A)) receptors in brain; this is the presumed basis of their action as anesthetics. In a previous study using the neuroactive steroid analog, (3alpha,5beta)-6-azi-3-hydroxypregnan-20-one (6-AziP), as a photoaffinity-labeling reagent, we showed that voltage-dependent anion channel-1 (VDAC-1) was the predominant protein labeled in brain. Antisera to VDAC-1 were shown to coimmunoprecipitate GABA(A) receptors, suggesting a functional relationship between steroid binding to VDAC-1 and modulation of GABA(A) receptor function. This study examines the contribution of steroid binding to VDAC proteins to modulation of GABA(A) receptor function and anesthesia. Photolabeling of 35-kDa protein with [(3)H]6-AziP was reduced 85% in brain membranes prepared from VDAC-1-deficient mice but was unaffected by deficiency of VDAC-3. The photolabeled 35-kDa protein in membranes from VDAC-1-deficient mice was identified by two-dimensional electrophoresis and electrospray ionization-tandem mass spectrometry as VDAC-2. The absence of VDAC-1 or VDAC-3 had no effect on the ability of neuroactive steroids to modulate GABA(A) receptor function as evidenced by radioligand ([(35)S] t-butylbicyclophosphorothionate) binding or by electrophysiological studies. Electrophysiological studies also showed that neuroactive steroids modulate GABA(A) receptor function normally in VDAC-2-deficient fibroblasts transfected with alpha(1)beta(2)gamma(2) GABA(A) receptor subunits. Finally, the neuroactive steroid pregnanolone [(3alpha,5beta)-3-hydroxypregnan-20-one] produced anesthesia (loss of righting reflex) in VDAC-1- and VDAC-3-deficient mice, and there was no difference in the recovery time between the VDAC-deficient mice and wild-type controls. These data indicate that neuroactive steroid binding to VDAC-1, -2, or -3 is unlikely to mediate GABA(A) receptor modulation or anesthesia.