Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to ...investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins, cell death, cell apoptosis, ROS generation and the ATP/AMPK pathway in Sertoli cells. The role of ROS, ER stress and the ATP/AMPK pathway in ZEA-induced cell-cycle arrest and cell apoptosis was explored by using the antioxidant NAC, ER stress inhibitor 4-PBA and the AMPK inhibitor dorsomorphin, respectively. The results revealed that ZEA inhibited the cell proliferation, influenced the distribution of the cell cycle and induced cell apoptosis through the ATP/AMPK pathway. The ATP/AMPK pathway was regulated by ER stress that was induced by ROS generation after exposure to ZEA. Taking these together, this study provided evidence that ROS regulated the process of ZEA-induced cell cycle arrest and cell apoptosis through ER stress and the ATP/AMPK signal ways.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC ...through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined.
Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis.
MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies.
MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Accumulating evidence suggests that neuroinflammation plays an important role in the progression of Parkinson's disease (PD). Excessively activated microglia produce several pro-inflammatory enzymes ...and pro-inflammatory cytokines, leading to damage to surrounding neurons and eventually inducing neurodegeneration. Therefore, the inhibition of microglial overactivation may be a potential therapeutic strategy to prevent the further progression of PD. β-Hydroxybutyric acid (BHBA) has been shown to suppress lipopolysaccharide (LPS)-induced inflammation in BV-2 cells and to protect dopaminergic neurons in previous studies, but the underlying mechanisms remain unclear. Thus, in this study, we further investigated this mechanism in LPS-induced in vivo and in vitro PD models.
For the in vitro experiments, primary mesencephalic neuron-glia cultures were pretreated with BHBA and stimulated with LPS. (3)Hdopamine (DA) uptake, tyrosine hydroxylase-immunoreactive (TH-ir) neurons and morphological analysis were evaluated and analyzed in primary mesencephalic neuron-glia cultures. In vivo, microglial activation and the injury of dopaminergic neurons were induced by LPS intranigral injection, and the effects of BHBA treatment on microglial activation and the survival ratio and function of dopaminergic neurons were investigated. Four our in vitro mechanistic experiment, primary microglial cells were pretreated with BHBA and stimulated with LPS; the cells were then assessed for the responses of pro-inflammatory enzymes and pro-inflammatory cytokines, and the NF-κB signaling pathway was evaluated and analyzed.
We found that BHBA concentration-dependently attenuated the LPS-induced decrease in (3)HDA uptake and loss of TH-ir neurons in the primary mesencephalic neuron/glia mixed culture. BHBA treatment significantly improved the motor dysfunction of the PD model rats induced by intranigral injection of LPS, and this beneficial effect of BHBA was attributed to the inhibition of microglial overactivation and the protection of dopaminergic neurons in the substantia nigra (SN). Our in vitro mechanistic study revealed that the inhibitory effect of BHBA on microglia was mediated by G-protein-coupled receptor 109A (GPR109A) and involved the NF-κB signaling pathway, causing the inhibition of pro-inflammatory enzyme (iNOS and COX-2) and pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) production.
In conclusion, the present study supports the effectiveness of BHBA in protecting dopaminergic neurons against inflammatory challenge.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Accelerated aging experiments of 3,3‐bis(azidomethyl)oxetane (BAMO) and tetrahydrofuran (THF) copolymers (molar ratio 1 : 1, marked as PBT prepolymer) and PBT elastomer at elevated temperatures were ...performed to explore the aging mechanism of PBT energetic elastomer during long‐term storage. The evolution of functional groups, plasticizer content, element chemical state and crosslinking density were studied by FT‐IR, HPLC, XPS and swelling method, respectively. Results show that: (1) Oxidation of terminal hydroxyl, oxidative crosslinking between binder macromolecules, chain breaking of polymers and degradation of −CH2N3 occurred during the thermal aging of PBT prepolymer, and antioxidant (BHT) could effectively delay the thermal aging process of PBT prepolymer by absorbing the active oxidation substances. (2) The relative contents of −C=O showed a cubic function with time, and the relative contents of −NO2 and −N3 changed linearly with time during the thermal aging of PBT elastomer. The relative contents of BDNPF and BDNPA declined linearly with time, and the thermal stability of BDNPF was better than that of BDNPA. (3) The thermal aging of PBT elastomer experienced three main reaction stages: degradation of carbamate, the oxidative crosslinking of molecular chain caused by the decomposition products of BDNPF/BDNPA, and chain breaking of the polymer system. In addition, a small amount of −CH2N3 decomposed throughout the whole aging process.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
We present
and
maps of six nearby star-forming galaxies, NGC 253, NGC 1068, IC 342, M82, M83, and NGC 6946, obtained with the James Clerk Maxwell Telescope as part of the MALATANG survey. ...All galaxies were mapped in the central 2′ × 2′ region at 14″ (FWHM) resolution (corresponding to linear scales of ∼0.2–1.0 kpc). The
L
IR
–
L
′
dense
relation, where the dense gas is traced by the
and the
emission, measured in our sample of spatially resolved galaxies is found to follow the linear correlation established globally in galaxies within the scatter. We find that the luminosity ratio,
L
IR
/
L
′
dense
, shows systematic variations with
L
IR
within individual spatially resolved galaxies, whereas the galaxy-integrated ratios vary little. A rising trend is also found between
L
IR
/
L
′
dense
ratio and the warm-dust temperature gauged by the 70
μ
m/100
μ
m flux ratio. We find that the luminosity ratios of IR/HCN (4–3) and IR/HCO
+
(4–3), which can be taken as a proxy for the star formation efficiency (SFE) in the dense molecular gas (SFE
dense
), appear to be nearly independent of the dense gas fraction (
f
dense
) for our sample of galaxies. The SFE of the total molecular gas (SFE
mol
) is found to increase substantially with
f
dense
when combining our data with those on local (ultra)luminous infrared galaxies and high-
z
quasars. The mean
line ratio measured for the six targeted galaxies is 0.9 ± 0.6. No significant correlation is found for the
ratio with the star formation rate as traced by
L
IR
, nor with the warm-dust temperature, for the different populations of galaxies.
ABSTRACT
Molecular gas plays a critical role in explaining the quiescence of star formation (SF) in massive isolated spiral galaxies, which could be a result of either the low molecular gas content ...and/or the low SF efficiency. We present IRAM 30-m observations of the CO lines in the Sombrero galaxy (NGC 4594), the most massive spiral at $d\lesssim 30\rm ~Mpc$. We detect at least one of the three CO lines covered by our observations in all 13 observed positions located at the galactic nucleus and along an $\sim 25\rm ~kpc$-diameter dusty ring. The total extrapolated molecular gas mass of the galaxy is $M_{\rm H_2}\approx 4\times 10^{8}\rm ~M_\odot$. The measured maximum CO gas rotation velocity of $\approx 381\rm ~km~s^{-1}$ suggests that NGC 4594 locates in a dark matter halo with a mass $M_{\rm 200}\gtrsim 10^{13}\rm ~M_\odot$. Comparing to other galaxy samples, NGC 4594 is extremely gas poor and SF inactive, but the SF efficiency is apparently not inconsistent with that predicted by the Kennicutt–Schmidt law, so there is no evidence of enhanced SF quenching in this extremely massive spiral with a huge bulge. We also calculate the predicted gas supply rate from various sources to replenish the cold gas consumed in SF, and find that the galaxy must experience a starburst stage at high redshift, then the leftover or recycled gas provides SF fuels to maintain the gradual growth of the galactic disc at a gentle rate.
•Activated microglia induced neuroinflammation in hippocampal CA1 and CA3 regions in mice.•Acetylated HMGB1 increased and mediated inflammation in hippocampal of mice after cold exposure.•Neuronal ...integrity in hippocampal CA1 and CA3 regions was destroyed after cold exposure.
Stress is a nonspecific response to adverse circumstances and chronic stress can destroy homeostasis, leading to various primary diseases. Although chronic cold stress is becoming increasingly important for individuals living or working in extreme environments, the risk of associated disorders of the central nervous system remains unstudied. Here, male C57BL/6 mice were exposed to a temperature of 4 °C, for three hours each day for one, two or three weeks. Glial cell activation, neuronal structure, and neuroinflammation were then evaluated by western blotting, immunofluorescence, Nissl staining and co-immunoprecipitation. Microglial activation, accompanied by activation of the NF-κB signaling pathway, release of pro-inflammatory cytokines and loss of Nissl bodies, was observed in mouse hippocampal tissue following cold exposure. We speculate that these phenomena are mediated by the HMGB1/TLR4/NF-κB pathway and closely associated with acetylation of HMGB1 in the hippocampus. These findings provide new insights into the mechanisms of the cold stress response, which should inform the development of new strategies to combat the effects of hypothermia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
Conjugated polymers present a compelling option for thermoelectric applications due to their low working temperatures, good compatibility with solution-processing techniques, and high potential for ...scalability. However, the inherently low electrical conductivities of the pristine conjugated polymers necessitate improvements
via
doping methods. Doping effectively enhances the electrical conductivity by increasing the charge concentration and mobility within the conjugated polymer matrix. Hence, the present study investigates the compatibility between a ferric chloride (FeCl
3
) dopant and four distinct conjugated polymers and evaluates the effects of the dopant/polymer combination on the thermoelectric properties of the material. First, the influence of backbone engineering is investigated
via
a comparison between 4-(3′,4′-difluoro-3,3′′-bis(2-hexyldecyl)-5′′-methyl-2,2′:5′,2′′-terthiophen-5-yl)-7-methylbenzo
c
1,2,5thiadiazole (
PC16BTF
) and 4-(3,3′′-bis(2-hexyldecyl)-5′′-methyl-2,2′:5′,2′′-terthiophen-5-yl)-7-methylbenzo
c
1,2,5thiadiazole (
PC16BTH
). These polymers differ in that
PC16BTF
incorporates two fluorine-atom substituents on the thiophene ring, while
PC16BTH
contains hydrogen atoms in these positions. Then, the effects of various side-chain lengths are investigated by comparing the abovementioned
PC16BTH
with both 4-(3,3′′-bis(2-butyloctyl)-5′′-methyl-2,2′:5′,2′′-terthiophen-5-yl)-7-methylbenzo
c
1,2,5thiadiazole (
PC12BTH
) and 4-methyl-7-(5′′-methyl-3,3′′-bis(2-octyldodecyl)-2,2′:5′,2′′-terthiophen-5-yl)benzo
c
1,2,5thiadiazole (
PC20BTH
). The FeCl
3
dopant was selected for its suitable size and charge transfer capability, which significantly influence the thermoelectric performance of each conjugated polymer. As a result,
PC16BTH
exhibits the highest power factor (PF) of 22.4 μW m
−1
K
−2
due to its moderate side-chain length and relatively high doping efficiency. Thus, the present study provides valuable insights into suitable strategies for improving the compatibility between dopants and polymers, thereby offering a promising avenue for further enhancing the thermoelectric performance of doped conjugated polymers.
Through designing molecules to enhance dopant miscibility, comprehensive research was conducted to optimize the thermoelectric performance.
We propose the question of the modulated structures of copper oxide is caused by the CuO2 in‐plane oxygen vacancy or apical oxygen vacancy. Sr2CuO3+δ single‐crystal samples were prepared using ...high‐temperature and high‐pressure methods. The major phase of Sr2CuO3+δ (δ = 0.4) single‐crystal system is found to be constituted by the 52 a modulated structure with the Fmmm space group, which originates from the CuO2 in‐plane oxygen vacancy appearing in octahedral Cu‐O. Besides, the presence of the CuO2 in‐plane oxygen vacancy may obliterate the superconductivity of the system. Experimental results deduce that the oxygen vacancy may appear in the apical oxygen sites in high‐temperature copper oxide superconductors.
The CuO2 in‐plane oxygen vacancy obliterates the superconductivity of the Sr2CuO3+δ (δ = 0.4) single crystal system. It can be deduced that the complete CuO2 planes (oxygen vacancy‐free) guarantee superconductivity in copper oxide high‐temperature superconductors in which oxygen vacancy only appears at the apical oxygen sites.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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