GNA13 suppresses proliferation of ER+ breast cancer cells via ERα dependent upregulation of the MYC oncogene.

GNA13 (Gα13) is one of two alpha subunit members of the G12/13 family of heterotrimeric G-proteins which mediate signaling downstream of GPCRs. It is known to be essential for embryonic development and vasculogenesis and has been increasingly shown to be involved in mediating several steps of cancer progression. Recent studies found that Gα13 can function as an oncogene and contributes to progression and metastasis of multiple tumor types, including ovarian, head and neck and prostate cancers. In most cases, Gα12 and Gα13, as closely related α-subunits in the subfamily, have similar cellular roles. However, in recent years their differences in signaling and function have started to emerge. We previously identified that Gα13 drives invasion of Triple Negative Breast Cancer (TNBC) cells in vitro. As a highly heterogenous disease with various well-defined molecular subtypes (ER+ /Her2-, ER+ /Her2+, Her2+, TNBC) and subtype associated outcomes, the function(s) of Gα13 beyond TNBC should be explored. Here, we report the finding that low expression of GNA13 is predictive of poorer survival in breast cancer, which challenges the conventional idea of Gα12/13 being universal oncogenes in solid tumors. Consistently, we found that Gα13 suppresses the proliferation in multiple ER+ breast cancer cell lines (MCF-7, ZR-75-1 and T47D). Loss of GNA13 expression drives cell proliferation, soft-agar colony formation and in vivo tumor formation in an orthotopic xenograft model. To evaluate the mechanism of Gα13 action, we performed RNA-sequencing analysis on these cell lines and found that loss of GNA13 results in the upregulation of MYC signaling pathways in ER+ breast cancer cells. Simultaneous silencing of MYC reversed the proliferative effect from the loss of GNA13, validating the role of MYC in Gα13 regulation of proliferation. Further, we found Gα13 regulates the expression of MYC, at both the transcript and protein level in an ERα dependent manner. Taken together, our study provides the first evidence for a tumor suppressive role for Gα13 in breast cancer cells and demonstrates for the first time the direct involvement of Gα13 in ER-dependent regulation of MYC signaling. With a few exceptions, elevated Gα13 levels are generally considered to be oncogenic, similar to Gα12. This study demonstrates an unexpected tumor suppressive role for Gα13 in ER+ breast cancer via regulation of MYC, suggesting that Gα13 can have subtype-dependent tumor suppressive roles in breast cancer.

The C4 photosynthesis bifunctional enzymes, PDRPs, of maize are co-opted to cytoplasmic viral replication complexes to promote infection of a prevalent potyvirus sugarcane mosaic virus.

In maize, two pyruvate orthophosphate dikinase (PPDK) regulatory proteins, ZmPDRP1 and ZmPDRP2, are respectively specific to the chloroplast of mesophyll cells (MCs) and bundle sheath cells (BSCs). Functionally, ZmPDRP1/2 catalyse both phosphorylation/inactivation and dephosphorylation/activation of ZmPPDK, which is implicated as a major rate-limiting enzyme in C4 photosynthesis of maize. Our study here showed that maize plants lacking ZmPDRP1 or silencing of ZmPDRP1/2 confer resistance to a prevalent potyvirus sugarcane mosaic virus (SCMV). We verified that the C-terminal domain (CTD) of ZmPDRP1 plays a key role in promoting viral infection while independent of enzyme activity. Intriguingly, ZmPDRP1 and ZmPDRP2 re-localize to cytoplasmic viral replication complexes (VRCs) following SCMV infection. We identified that SCMV-encoded cytoplasmic inclusions protein CI targets directly ZmPDRP1 or ZmPDRP2 or their CTDs, leading to their re-localization to cytoplasmic VRCs. Moreover, we found that CI could be degraded by the 26S proteasome system, while ZmPDRP1 and ZmPDRP2 could up-regulate the accumulation level of CI through their CTDs by a yet unknown mechanism. Most importantly, with genetic, cell biological and biochemical approaches, we provide evidence that BSCs-specific ZmPDRP2 could accumulate in MCs of Zmpdrp1 knockout (KO) lines, revealing a unique regulatory mechanism crossing different cell types to maintain balanced ZmPPDK phosphorylation, thereby to keep maize normal growth. Together, our findings uncover the genetic link of the two cell-specific maize PDRPs, both of which are co-opted to VRCs to promote viral protein accumulation for robust virus infection.

Understanding the glassy dynamics from melting temperatures in binary glass-forming liquids.

It is natural to expect that small particles in binary mixtures move faster than large ones. However, in binary glass-forming liquids with soft-core particle interactions, we observe the counterintuitive dynamic reversal between large and small particles along with the increase of pressure by performing molecular dynamics simulations. The structural relaxation (dynamic heterogeneity) of small particles is faster (weaker) than large ones at low pressures, but becomes slower (stronger) above a crossover pressure. In contrast, this dynamic reversal never happens in glass-forming liquids with hard-core interactions. We find that the difference of the effective melting temperatures felt by large and small particles can be used to understand the dynamic reversal. In binary mixtures, we derive effective melting temperatures of large and small particles simply from the conversion of units and find that particles with a higher effective melting temperature usually undergo a slower and more heterogeneous relaxation. The presence (absence) of the dynamic reversal in soft-core (hard-core) systems is simply due to the non-monotonic (monotonic) behavior of the melting temperature as a function of pressure. Interestingly, by manipulating the relative softness between large and small particles, we obtain a special case of soft-core systems, in which large particles always have higher effective melting temperatures than small ones. As a result, the dynamic reversal is totally eliminated. Our work provides another piece of evidence of the underlying connections between the properties of non-equilibrium glass-formers and equilibrium crystal-formers.

Boosting Cu─In─Zn─S-based Quantum-Dot Light-Emitting Diodes Enabled by Engineering Cu─NiOx /PEDOT:PSS Bilayered Hole-Injection Layer.

The imbalance of charge injection is considered to be a major factor that limits the device performance of cadmium-free quantum-dot light-emitting diodes (QLEDs). In this work, high-performance cadmium-free Cu─In─Zn─S(CIZS)-based QLEDs are designed and fabricated through tailoring interfacial energy level alignment and improving the balance of charge injection. This is achieved by introducing a bilayered hole-injection layer (HIL) of Cu-doped NiOx (Cu─NiOx )/Poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS). High-quality Cu─NiOx film is prepared through a novel and straightforward sol-gel procedure. Multiple experimental characterizations and theoretical calculations show that the incorporation of Cu2+ ions can regulate the energy level structure of NiOx and enhance the hole mobility. The state-of-art CIZS-based QLEDs with Cu─NiOx /PEDOT:PSS bilayered HIL exhibit the maximum external quantum efficiency of 6.04% and half-life time of 48 min, which is 1.3 times and four times of the device with only PEDOT:PSS HIL. The work provides a new pathway for developing high-performance cadmium-free QLEDs.

Scaling of the non-phononic spectrum of two-dimensional glasses.

Low-frequency vibrational harmonic modes of glasses are frequently used to rationalize their universal low-temperature properties. One well studied feature is the excess low-frequency density of states over the Debye model prediction. Here, we examine the system size dependence of the density of states for two-dimensional glasses. For systems of fewer than 100 particles, the density of states scales with the system size as if all the modes were plane-wave-like. However, for systems greater than 100 particles, we find a different system-size scaling of the cumulative density of states below the first transverse sound mode frequency, which can be derived from the assumption that these modes are quasi-localized. Moreover, for systems greater than 100 particles, we find that the cumulative density of states scales with the frequency as a power law with the exponent that leads to the exponent ß = 3.5 for the density of states. For systems whose sizes were investigated, we do not see a size-dependence of exponent ß.

Electroluminescent white light-emitting diodes with cadimum-free Cu-In-Zn-S nanocrystals sandwiched between two TFB layers.

A high color rendering index (CRI) and stable spectra under different voltages are important parameters for large-area planar light sources. However, the spectrum of most electroluminescent white light-emitting diodes (el-WLEDs) with a single emissive layer (EML) varies with a changing voltage. Herein, an el-WLED is fabricated based on Cd-free Cu-In-Zn-S (CIZS)/ZnS nanocrystals (NCs) and poly [(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(p-butylphenyl))diphenylamine)] (TFB) as double EMLs, which exhibit white-light emission with a high CRI value of 91 and commission internationale de l'éclairage (CIE) color coordinates of (0.33, 0.33). Meanwhile, it has a stable spectrum under voltage up to 7 V and a maximum luminance up to 679 cd/m2 with a low turn-on voltage of 2.2 V. This work provides a foundation for Cd-free el-WLEDs with high CRI and stable spectra.

Erratum: Low-Frequency Excess Vibrational Modes in Two-Dimensional Glasses [Phys. Rev. Lett. 127, 248001 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.127.248001.

Density of states below the first sound mode in 3D glasses.

Glasses feature universally low-frequency excess vibrational modes beyond Debye prediction, which could help rationalize, e.g., the glasses' unusual temperature dependence of thermal properties compared to crystalline solids. The way the density of states of these low-frequency excess modes D(ω) depends on the frequency ω has been debated for decades. Recent simulation studies of 3D glasses suggest that D(ω) scales universally with ω4 in a low-frequency regime below the first sound mode. However, no simulation study has ever probed as low frequencies as possible to test directly whether this quartic law could work all the way to extremely low frequencies. Here, we calculated D(ω) below the first sound mode in 3D glasses over a wide range of frequencies. We find D(ω) scales with ωß with ß < 4 at very low frequencies examined, while the ω4 law works only in a limited intermediate-frequency regime in some glasses. Moreover, our further analysis suggests our observation does not depend on glass models or glass stabilities examined. The ω4 law of D(ω) below the first sound mode is dominant in current simulation studies of 3D glasses, and our direct observation of the breakdown of the quartic law at very low frequencies thus leaves an open but important question that may attract more future numerical and theoretical studies.

Optimization and Preparation of Tallow with a Strong Aroma by Mild Oxidation.

This study was performed to extract and separate the volatiles with solid-phase microextraction (SPME), and was conducted to analyze volatile odor compounds qualitatively and quantitatively in the production of a strong aroma tallow by mild oxidation. A total of 51 odor compounds were detected in the tallow smelted under different conditions. It was found that the high proportion of aldehydes was an important feature of the aroma components in the oxidized melted tallow, such as 1-hexanal, heptanal, nonanal, octanal, benzaldehyde, etc. Through the determination of various indicators, sensory evaluation, and the gas chromatography-olfaction-mass spectrometry (GC-O-MS) analysis and, in combination with response surface methodology, the optimal process parameters for oxidative smelting of tallow were determined as follows: a reaction temperature of 149.61 °C, a reaction time of 31.68 min, and an airflow rate of 97.44 L/h. The accelerated oxidation test further verified the quality of the oxidized tallow.

Low-Frequency Excess Vibrational Modes in Two-Dimensional Glasses.

Glasses possess more low-frequency vibrational modes than predicted by Debye theory. These excess modes are crucial for the understanding of the low temperature thermal and mechanical properties of glasses, which differ from those of crystalline solids. Recent simulational studies suggest that the density of the excess modes scales with their frequency ω as ω^{4} in two and higher dimensions. Here, we present extensive numerical studies of two-dimensional model glass formers over a large range of glass stabilities. We find that the density of the excess modes follows D_{exc}(ω)∼ω^{2} up to around the boson peak, regardless of the glass stability. The stability dependence of the overall scale of D_{exc}(ω) correlates with the stability dependence of low-frequency sound attenuation. However, we also find that, in small systems, where the first sound mode is pushed to higher frequencies, at frequencies below the first sound mode, there are excess modes with a system size independent density of states that scales as ω^{3}.

Solution-processed double-layered hole transport layers for highly-efficient cadmium-free quantum-dot light-emitting diodes.

The search for heavy-metal-free quantum-dot light-emitting diodes (QD-LEDs) has greatly intensified in the past few years because device performance still falls behind that of CdSe-based QD-LEDs. Apart from the effects of nanostructures of the emitting materials, the unbalanced charge injection and transport severely affects the performance of heavy-metal-free QD-LEDs. In this work, we presented solution-processed double hole transport layers (HTLs) for improving the device performance of heavy-metal-free Cu-In-Zn-S(CIZS)/ZnS-based QD-LEDs, in which N,N'-Bis(3-methylphenyl)-N,N'-bis(phenyl)benzidine (TPD) as an interlayer was incorporated between the emitting layer and the HTL. Through optimizing the thickness of poly(9,9-dioctylfluorene-co-N-(4-butylphenyl)diphenyl-amine (TFB) and TPD layers, a maximum external quantum efficiency (ηEQE) of 3.87% and a current efficiency of 9.20 cd A-1 were achieved in the solution-processed QD-LEDs with double-layered TFB/TPD as the HTLs, which were higher than those of the devices with pristine TFB, TPD and TFB:TPD blended layers. The performance enhancement could be attributed to the synergistic effects of the reduction of the hole injection barrier, the increase of the hole mobility and suppressed charge transfer between the HTL and the emitting layer. Furthermore, the best ηEQE of 5.61% with a mean ηEQE of 4.44 ± 0.73% was realized in the Cu-In-Zn-S-based QD-LEDs by varying the annealing temperature of TPD layer due to the more balanced charge injection and transport as well as smooth surface of TPD layer.

Sound attenuation in finite-temperature stable glasses.

The temperature dependence of the thermal conductivity of amorphous solids is markedly different from that of their crystalline counterparts, but exhibits universal behaviour. Sound attenuation is believed to be related to this universal behaviour. Recent computer simulations demonstrated that in the harmonic approximation sound attenuation Γ obeys quartic, Rayleigh scattering scaling for small wavevectors k and quadratic scaling for wavevectors above the Ioffe-Regel limit. However, simulations and experiments do not provide a clear picture of what to expect at finite temperatures where anharmonic effects become relevant. Here we study sound attenuation at finite temperatures for model glasses of various stability, from unstable glasses that exhibit rapid aging to glasses whose stability is equal to those created in laboratory experiments. We find several scaling laws depending on the temperature and stability of the glass. First, we find the large wavevector quadratic scaling to be unchanged at all temperatures. Second, we find that at small wavevectors Γ∼k1.5 for an aging glass, but Γ∼k2 when the glass does not age on the timescale of the calculation. For our most stable glass, we find that Γ∼k2 at small wavevectors, then a crossover to Rayleigh scattering scaling Γ∼k4, followed by another crossover to the quadratic scaling at large wavevectors. Our computational observation of this quadratic behavior reconciles simulation, theory and experiment, and will advance the understanding of the temperature dependence of thermal conductivity of glasses.

Energy transport in glasses.

The temperature dependence of the thermal conductivity is linked to the nature of the energy transport at a frequency ω, which is quantified by thermal diffusivity d(ω). Here we study d(ω) for a poorly annealed glass and a highly stable glass prepared using the swap Monte Carlo algorithm. To calculate d(ω), we excite wave packets and find that the energy moves diffusively for high frequencies up to a maximum frequency, beyond which the energy stays localized. At intermediate frequencies, we find a linear increase of the square of the width of the wave packet with time, which allows for a robust calculation of d(ω), but the wave packet is no longer well described by a Gaussian as for high frequencies. In this intermediate regime, there is a transition from a nearly frequency independent thermal diffusivity at high frequencies to d(ω) ∼ ω-4 at low frequencies. For low frequencies the sound waves are responsible for energy transport and the energy moves ballistically. The low frequency behavior can be predicted using sound attenuation coefficients.

Differences and Correlations of Morphological Characteristics and Fatty Acid Profiles of Seeds of Toona sinensis.

Toona sinensis (A.Juss.) M.Roem., a multi-purpose tree of Meliaceae, is widely distributed and intensively cultivated in Asia, yet its high yielding, lipid-rich seeds are rarely exploited. The present study systematically analyzed the differences and correlations of seed morphological characteristics and fatty acid (FA) profiles of 62 representative T. sinensis germplasms distributed across northern to southern China. T. sinensis seeds were rich in total FAs (TFA, 107.03-176.18 mg/g). Additionally, linoleic acid (54.69-100.59 mg/g), α-linolenic acid (ALA, 22.47-45.02 mg/g), oleic acid (OA, 5.12-23.94 mg/g), palmitic acid (6.87-14.14 mg/g), stearic acid (SA, 3.13-6.57 mg/g) and elaidic acid (1.70-2.88 mg/g) were the major FAs measured by GC/MS analysis. Size (average width of 3.94±0.01 mm and length of 5.79±0.02 mm) and mass (average thousand-seed weight of 10.52±0.17 g) were greater in T. sinensis seeds collected south than north of 30° latitude. These traits were also positively correlated with unsaturated FA content and negatively related to SA and saturated FA contents (P<0.05). Significant positive correlations were found between seed length and polyunsaturated FA (R2 =0.370) and ALA levels (R2 =0.296), as well as between thousand-seed weight and monounsaturated FAs (R2 =0.309) and OA levels (R2 =0.297) (P<0.05). Seventeen T. sinensis germplasms gathered by cluster analysis as cluster IV were determined as desirable for oil processing due to their higher TFA and ALA contents and greater seed size and mass than others. Generally, the wider, heavier, and especially longer seeds of T. sinensis contain much higher levels of FAs, especially ALA, and are the more promising sources for breeding and the oil processing industry.

Reactive oxygen species regulate miR-17-5p expression via DNA methylation in paraquat-induced nerve cell damage.

There is emerging evidence suggesting that oxidative stress and DNA methylation can alter miRNA expression. However, little is known on the mechanism of miR-17-5p expression changes in paraquat (PQ)-induced nerve cell damage. In the present study, neuro-2a cells were pretreated with antioxidant N-acetylcysteine (NAC) or DNA methylation inhibitor decitabine (DAC), then exposed to different concentrations of PQ, while the expression levels of miR-17-5p were detected by qRT-PCR. Here, it is showed that PQ downregulated the expression of miR-17-5p dose-dependently in neuro-2a cells. The DNA methylation level was upregulated after PQ exposure, while downregulated with the pretreatment of NAC in the above content, detected by 5-mC immunofluorescence technique. The interaction effect of NAC and PQ in alternating DNA methylation level was further confirmed by flow cytometry. NAC and DAC individually had an interaction effect in PQ-induced nerve cell damage. After using NAC, PQ-induced ROS elevation and DNA methylation are reduced, thereby preventing the proapoptotic effect of miR-17-5p. Above all, PQ can induce DNA methylation variations through ROS production, leading to the downregulation of miR-17-5p expression in PQ-induced nerve cell damage.

Sound attenuation in stable glasses.

Understanding the difference between the universal low-temperature properties of amorphous and crystalline solids requires an explanation for the stronger damping of long-wavelength phonons in amorphous solids. A longstanding sound attenuation scenario, resulting from a combination of experiments, theories, and simulations, leads to a quartic scaling of sound attenuation with the wavevector, which is commonly attributed to the Rayleigh scattering of sound. Modern computer simulations offer conflicting conclusions regarding the validity of this picture. We simulate glasses with an unprecedentedly broad range of stabilities to perform the first microscopic analysis of sound damping in model glass formers across a range of experimentally relevant preparation protocols. We present convincing evidence that quartic scaling is recovered for small wavevectors irrespective of the glass's stability. With increasing stability, the wavevector where the quartic scaling begins increases by approximately a factor of three and the sound attenuation decreases by over an order of magnitude. Our results uncover an intimate connection between glass stability and sound damping.

Revealing the Link between Structural Relaxation and Dynamic Heterogeneity in Glass-Forming Liquids.

Despite the use of glasses for thousands of years, the nature of the glass transition is still mysterious. On approaching the glass transition, the growth of dynamic heterogeneity has long been thought to play a key role in explaining the abrupt slowdown of structural relaxation. However, it still remains elusive whether there is an underlying link between structural relaxation and dynamic heterogeneity. Here, we unravel the link by introducing a characteristic time scale hiding behind an identical dynamic heterogeneity for various model glass-forming liquids. We find that the time scale corresponds to the kinetic fragility of liquids. Moreover, it leads to scaling collapse of both the structural relaxation time and dynamic heterogeneity for all liquids studied, together with a characteristic temperature associated with the same dynamic heterogeneity. Our findings imply that studying the glass transition from the viewpoint of dynamic heterogeneity is more informative than expected.

Impacts of Pantoea agglomerans strain and cation-modified clay minerals on the adsorption and biodegradation of phenanthrene.

Interactions between microorganisms and minerals have the potential contribution to remove polycyclic aromatic hydrocarbons (PAHs) in model systems. In this study, phenanthrene (PHE) was used as a probe molecule to explore the potential adsorption and biotransformation processes in the presence of microorganisms and various reference clays, such as montmorillonite (M), kaolinite (K), and pyrophyllite (P). Equilibrium adsorption experiments and scanning electron microscopy (SEM) technique were used to investigate the sorption of Pantoea agglomerans strains on clay minerals saturated with cations (Na+ and Fe3+). The adsorption isotherms of PHE and Pantoea agglomerans strains on cation-modified clay minerals fitted to Langmuir equation, and their adsorbed amounts both followed the sequence: montmorillonite > kaolinite > pyrophyllite. For six types of cation-modified minerals, the behavior of PHE adsorbed and Pantoea agglomerans adhered onto mentioned minerals was in the order of Na(I)-M > Fe(Ⅲ)-M, Na(I)-K > Fe(Ⅲ)-K and Fe(Ⅲ)-P > Na(I)-P, respectively. The biodegradation results showed that cation-modified clay minerals could enhance the biodegradation of PHE, ascribing to their large specific surface area, and cation exchange capability, as well as the difference in zeta potential between minerals and Pantoea agglomerans strains. Comparison of biodegradation rates displayed that PHE was degraded the highest in the presence of Na-M (93.285%). In addition, the obtained results suggested that the adhesion of bacteria onto cation-exchanged clay minerals was beneficial to the biodegradation of PHE. Anthracen-9-ylmethanol and 3,4-dimethyl-2-(3-methylbutanoyl)benzoic acid were detected as the main intermediate compounds, which can be further biodegraded into small molecules. The overall results obtained in this study are of valuable significance for the understanding of the behavior of PHE in soil and associated environment.

Pretreatment neutrophil/lymphocyte ratio but not platelet/lymphocyte ratio has a prognostic impact in multiple myeloma.

BACKGROUND: We evaluated the prognostic significance of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with multiple myeloma (MM). METHODS: In total, we retrospectively analyzed 315 newly diagnosed MM patients and calculated NLR and PLR from the complete blood count of the untreated patients. We further assessed the role of pretreatment NLR and PLR on overall survival (OS) and progression-free survival (PFS). RESULTS: Multiple myeloma patients with high NLR (≥2) experienced shorter OS (P=.02) and PFS (P=.01) compared with patients with low NLR (<2). Furthermore, among the patients with conventional chemotherapy, elderly patients, or patients with advanced stages, high NLR (≥2) was found to have a negative prognostic impact on OS and PFS. In the multivariate Cox analysis, we confirmed that the NLR was an independent prognostic factor for both OS and PFS (P=.000). But the differences in OS or PFS by PLR were not found in MM patients. CONCLUSIONS: Our study suggests that NLR not PLR can be acted as an independent prognostic factor for analyzing the clinical outcome of MM patients.

The correlation between fragility, density, and atomic interaction in glass-forming liquids.

The fragility that controls the temperature-dependent viscous properties of liquids as the glass transition is approached, in various glass-forming liquids with different softness of the repulsive part of atomic interactions at different densities, is investigated by molecular dynamic simulations. We show that the landscape of fragility in purely repulsive systems can be separated into three regions denoted as RI, RII, and RIII, respectively, with qualitatively disparate dynamic behaviors: RI which can be described by "softness makes strong glasses," RII where fragility is independent of softness and can only be tuned by density, and RIII with constant fragility, suggesting that density plays an unexpected role for understanding the repulsive softness dependence of fragility. What is more important is that we unify the long-standing inconsistence with respect to the repulsive softness dependence of fragility by observing that a glass former can be tuned more fragile if nonperturbative attraction is added into it. Moreover, we find that the vastly dissimilar influences of attractive interaction on fragility could be estimated from the structural properties of related zero-temperature glasses.