Hearing impairment affects many older adults but is often diagnosed decades after speech comprehension in noisy situations has become effortful. Accurate assessment of listening effort may thus help ...diagnose hearing impairment earlier. However, pupillometry-the most used approach to assess listening effort-has limitations that hinder its use in practice. The current study explores a novel way to assess listening effort through eye movements. Building on cognitive and neurophysiological work, we examine the hypothesis that eye movements decrease when speech listening becomes challenging. In three experiments with human participants from both sexes, we demonstrate, consistent with this hypothesis, that fixation duration increases and spatial gaze dispersion decreases with increasing speech masking. Eye movements decreased during effortful speech listening for different visual scenes (free viewing, object tracking) and speech materials (simple sentences, naturalistic stories). In contrast, pupillometry was less sensitive to speech masking during story listening, suggesting pupillometric measures may not be as effective for the assessments of listening effort in naturalistic speech-listening paradigms. Our results reveal a critical link between eye movements and cognitive load, suggesting that neural activity in the brain regions that support the regulation of eye movements, such as frontal eye field and superior colliculus, are modulated when listening is effortful.
Assessment of listening effort is critical for early diagnosis of age-related hearing loss. Pupillometry is most used but has several disadvantages. The current study explores a novel way to assess listening effort through eye movements. We examine the hypothesis that eye movements decrease when speech listening becomes effortful. We demonstrate, consistent with this hypothesis, that fixation duration increases and gaze dispersion decreases with increasing speech masking. Eye movements decreased during effortful speech listening for different visual scenes (free viewing, object tracking) and speech materials (sentences, naturalistic stories). Our results reveal a critical link between eye movements and cognitive load, suggesting that neural activity in brain regions that support the regulation of eye movements are modulated when listening is effortful.
Core-shell type 'nanoghosts' were synthesized with a drug-loaded biodegradable PLGA core and a monocyte cell membrane-derived shell. The nanoghosts were monodisperse with an average size <200 nm, and ...showed good serum stability for 120 h. Doxorubicin-loaded nanoghosts showed greater cellular uptake and cytotoxicity compared to non-coated nanoparticle controls in metastatic MCF-7 breast cancer cell lines.
Close white dwarf binaries consisting of a white dwarf and an A-, F-, G-, or K-type main-sequence star, henceforth close WD+AFGK binaries, are ideal systems to understand the nature of type Ia ...supernovae progenitors and to test binary evolution models. In this work we identify 775 WD+AFGK candidates from TGAS (The Tycho-Gaia Astrometric Solution) and Gaia Data Release 2 (DR2), a well-defined sample of stars with available parallaxes, and we measure radial velocities (RVs) for 275 of them with the aim of identifying close binaries. The RVs have been measured from high-resolution spectra obtained at the Xinglong 2.16 m Telescope and the San Pedro Mártir 2.12 m Telescope and/or from available LAMOST DR6 (low-resolution) and RAVE DR5 (medium-resolution) spectra. We identify 23 WD+AFGK systems displaying more than 3 RV variation among 151 systems for which the measured values are obtained from different nights. Our WD+AFGK binary sample contains both AFGK dwarfs and giants, with a giant fraction ∼43%. The close binary fractions we determine for the WD+AFGK dwarf and giant samples are 24% and 15%, respectively. We also determine the stellar parameters (i.e., effective temperature, surface gravity, metallicity, mass, and radius) of the AFGK companions with available high-resolution spectra. The stellar parameter distributions of the AFGK companions that are members of close and wide binary candidates do not show statistically significant differences.
The aim of this study was to elucidate the exact role of microRNA-98-5p (miRNA-98-5p) in the progression of osteosarcoma and to explore its potential mechanism.
The expression levels of miRNA-98-5p ...and cell division cycle 25 (CDC25A) in osteosarcoma tissues and cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, the correlation between expressions of miRNA-98-5p and CDC25A and the survival of osteosarcoma patients was analyzed. After altering miRNA-98-5p and CDC25A expressions by liposome transfection, the expression levels of CDC25A, ki67, Cyclin D1, p21, BCL2-Associated X (BAX), B-cell lymphoma-2 (BCL-2) and BCL-XL in osteosarcoma cells were detected. Subsequently, potential binding sites between miRNA-98-5p and CDC25A were predicted and further verified by miRanda and Dual-Luciferase reporter gene assay, respectively. Regulatory effects of miRNA-98-5p and CDC25A on the migratory ability of osteosarcoma cells were evaluated by transwell assay. Moreover, nude mice were subcutaneously implanted with MG-63 cells over-expressing miRNA-98-5p or negative control. In addition, the functions of miRNA-98-5p and CDC25A in tumor-bearing nude mice were explored in vivo.
MiRNA-98-5p was lowly expressed in osteosarcoma tissues and cell lines, whereas CDC25A was highly expressed. Survival analysis showed that the survival of osteosarcoma patients with low-level of miRNA-98-5p or high-level of CDC25A was significantly worse. Besides, a negative correlation was identified between miRNA-98-5p and CDC25A. Subsequent experiments revealed that miRNA-98-5p significantly inhibited cell cycle progression and migratory potential, whereas induced the apoptosis of osteosarcoma cells by down-regulating CDC25A.
MiRNA-98-5p is lowly expressed, while CDC25A is highly expressed in osteosarcoma. Furthermore, miRNA-98-5p regulates cell cycle progression by down-regulating CDC25A, thus inhibiting the progression of osteosarcoma.
There are limited data comparing the prognosis and fertility outcomes of the patients with early cervical cancer treated by trans-vaginal radical trachelectomy (VRT) or abdominal radical ...trachelectomy (ART).The objective of this study was to compare the surgical and pathologic characteristics, the prognosis and fertility outcomes of the patients treated by VRT or ART.
Matched-case study based on a prospectively maintained database of patients underwent radical trachelectomy in 10 centres of China was designed to compare the prognosis and fertility outcomes of the patients treated by VRT or ART.
Totally 150 cases, 77 in the VRT and 73 in the ART group, were included. VRT and ART provide similar surgical and pathological outcomes except larger specimens obtained by ART. In the ART group, no patient developed recurrent diseases, but, in the VRT group, 7 (9.8%) patients developed recurrent diseases and 2 (1.6%) patients died of the tumours (P=0.035). The rate of pregnancy in the VRT group was significantly higher than those of ART (39.5% vs 8.8%; P=0.003). The patients with tumour size >2 cm showed significant higher recurrent rate (11.6% vs 2.4%, P<0.05) and lower pregnant rate (12.5% vs 32.1%, P=0.094) compared with the patients with tumour size <2 cm.
Patients treated by ART obtained better oncology results, but their fertility outcomes were unfavourable compared with VRT. Tumour size <2 cm should be emphasised as an indication for radical trachelectomy for improving the outcome of fertility and prognosis.
Vanilloid receptor type 1 (TRPV1) is a ligand-gated nonselective cation channel that is considered to be an important integrator of various pain stimuli such as endogenous lipids, capsaicin, heat, ...and low pH. In addition to expression in primary afferents, TRPV1 is also expressed in the CNS. To test the hypothesis that the CNS plays a differential role in the effect of TRPV1 antagonists in various types of pain, the analgesic effects of two TRPV1 antagonists with similar in vitro potency but different CNS penetration were compared in vivo. Oral administration of either A-784168 (1-3-(trifluoromethyl)pyridin-2-yl-N-4-(trifluoromethylsulfonyl)phenyl-1,2,3,6-tetrahydropyridine-4-carboxamide) (good CNS penetration) or A-795614 (N-1H-indazol-4-yl-N'-(1R)-5-piperidin-1-yl-2,3-dihydro-1H-inden-1-ylurea) (poor CNS penetration) blocked capsaicin-induced acute pain with the same potency. In complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, oral administration of either compound blocked thermal hyperalgesia with similar potency. Furthermore, intraplantar or intrathecal administration of A-784168 blocked CFA-induced thermal hyperalgesia, suggesting that both peripheral and CNS TRPV1 receptors may play a role in inflammatory thermal hyperalgesia. The effects of the two TRPV1 antagonists were further assessed in models presumably mediated by central sensitization, including CFA- and capsaicin-induced mechanical allodynia and osteoarthritic pain. In these models, the potency of the two compounds was similar after intrathecal administration. However, when administered orally, A-784168, with good CNS penetration, was much more potent than A-795614. Together, these results demonstrate that TRPV1 receptors in the CNS play an important role in pain mediated by central sensitization. In addition, these results demonstrate that significant CNS penetration is necessary for a TRPV1 antagonist to produce broad-spectrum analgesia.
To study the effects of application of salicylic acid (SA) on the antioxidant system and photosystem II (PS II) in wheat seedlings we used two different experiments. The first method was carried out ...by immersing roots in Hoagland’s nutrient solution containing 0, 0.25, or 2.5 mM SA, and the second method was performed by spraying two-week-old seedlings with the same SA concentrations. After 24 h, chlorophyll fluorescence, thylakoid membrane proteins, antioxidant enzyme activities, and reactive oxygen species were measured. The low concentration of SA caused a significant increase in the antioxidant enzyme activities. However, the treatment with 2.5 mM SA resulted in an increase in the non-photochemical quenching coefficient and a decrease in the antioxidant enzyme activities, the quantum yield of PS II photochemistry, and the photochemical quenching, especially in the first method of application. All these results indicate that the effects of SA on PS II and the antioxidative defense system were dependent on the concentration used and the method of application.
The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a key component of tumor necrosis factor (TNF)-induced necroptosis and plays a crucial role in necroptosis execution. However, the ...mechanisms that control MLKL activity are not completely understood. Here, we identify the molecular chaperone Hsp90 as a novel MLKL-interacting protein. We show that Hsp90 associates with MLKL and is required for MLKL stability. Moreover, we find that Hsp90 also regulates the stability of the upstream RIP3 kinase. Interference with Hsp90 function with the 17AAG inhibitor destabilizes MLKL and RIP3, resulting in their degradation by the proteasome pathway. Furthermore, we find that Hsp90 is required for TNF-stimulated necrosome assembly. Disruption of Hsp90 function prevents necrosome formation and strongly reduces MLKL phosphorylation and inhibits TNF-induced necroptosis. Consistent with a positive role of Hsp90 in necroptosis, coexpression of Hsp90 increases MLKL oligomerization and plasma membrane translocation and enhances MLKL-mediated necroptosis. Our findings demonstrate that an efficient necrotic response requires a functional Hsp90.
The precise measurement of cosmic-ray antinuclei serves as an important means for identifying the nature of dark matter and other new astrophysical phenomena, and could be used with other cosmic-ray ...species to understand cosmic-ray production and propagation in the Galaxy. For instance, low-energy antideuterons would provide a “smoking gun” signature of dark matter annihilation or decay, essentially free of astrophysical background. Studies in recent years have emphasized that models for cosmic-ray antideuterons must be considered together with the abundant cosmic antiprotons and any potential observation of antihelium. Therefore, a second dedicated Antideuteron Workshop was organized at UCLA in March 2019, bringing together a community of theorists and experimentalists to review the status of current observations of cosmic-ray antinuclei, the theoretical work towards understanding these signatures, and the potential of upcoming measurements to illuminate ongoing controversies. This review aims to synthesize this recent work and present implications for the upcoming decade of antinuclei observations and searches. This includes discussion of a possible dark matter signature in the AMS-02 antiproton spectrum, the most recent limits from BESS Polar-II on the cosmic antideuteron flux, and reports of candidate antihelium events by AMS-02; recent collider and cosmic-ray measurements relevant for antinuclei production models; the state of cosmic-ray transport models in light of AMS-02 and Voyager data; and the prospects for upcoming experiments, such as GAPS. This provides a roadmap for progress on cosmic antinuclei signatures of dark matter in the coming years.
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