Major depressive disorder is a devastating mental illness leading to a lifetime prevalence of higher than 16% on individuals. The treatment delay and inevitable adverse effects are major limitations ...of current depression interventions. Emerging evidence indicates that curcumin produced significant antidepressant properties in depression in both rodents and humans without adverse effects. Therefore, it is necessary to further clarify the antidepressant actions of curcumin and the underlying mechanism in depressed patients. A total of 108 male adults aged between 31 and 59 years were systematically recruited in Tianjin Anding Hospital. Subjects were administered the Chinese version of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale that measures different scores of depressive symptoms. The subjects were asked to take 2 capsules containing either 1000 mg of curcumin or placebo soybean powder daily for 6 weeks on the basis of their current antidepressant medications. The plasma levels of interleukin 1β, tumor necrosis factor α, brain-derived neurotrophic factor, and salivary cortisol were measured by enzyme-linked immunosorbent assay before and after curcumin or placebo treatment during the 6-week procedure. Chronic supplementation with curcumin produced significant antidepressant behavioral response in depressed patients by reduction of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores. Furthermore, curcumin decreases inflammatory cytokines interleukin 1β and tumor necrosis factor α level, increases plasma brain-derived neurotrophic factor levels, and decreases salivary cortisol concentrations compared with placebo group. These findings indicate the potential benefits of further implications of supplementary administration of curcumin to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder.
Ischemia-reperfusion (I/R) induced acute kidney injury (AKI), characterized by excessive mitochondrial damage and cell apoptosis, remains a clinical challenge. Recent studies suggest that regulator ...of calcineurin 1 (RCAN1) regulates mitochondrial function in different cell types, but the underlying mechanisms require further investigation. Herein, we aim to explore whether RCAN1 involves in mitochondrial dysfunction in AKI and the exact mechanism. In present study, AKI was induced by I/R and cisplatin in RCAN1
mice and mice with renal tubular epithelial cells (TECs)-specific deletion of RCAN1. The role of RCAN1 in hypoxia-reoxygenation (HR) and cisplatin-induced injury in human renal proximal tubule epithelial cell line HK-2 was also examined by overexpression and knockdown of RCAN1. Mitochondrial function was assessed by transmission electron microscopy, JC-1 staining, MitoSOX staining, ATP production, mitochondrial fission and mitophagy. Apoptosis was detected by TUNEL assay, Annexin V-FITC staining and Western blotting analysis of apoptosis-related proteins. It was found that protein expression of RCAN1 was markedly upregulated in I/R- or cisplatin-induced AKI mouse models, as well as in HR models in HK-2 cells. RCAN1 deficiency significantly reduced kidney damage, mitochondrial dysfunction, and cell apoptosis, whereas RCAN1 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration demonstrated that RCAN1 increases the phosphorylation of mitochondrial fission factor (Mff) by binding to downstream c-Jun N-terminal kinase (JNK), then promotes dynamin related protein 1 (Drp1) migration to mitochondria, ultimately leads to excessive mitochondrial fission of renal TECs. In conclusion, our study suggests that RCAN1 could induce mitochondrial dysfunction and apoptosis by activating the downstream JNK/Mff signaling pathway. RCAN1 may be a potential therapeutic target for conferring protection against I/R- or cisplatin-AKI.
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•Sorbent with CaO/Al2O3 mass ratio of 8:2 obtained the best cyclic sorption performance.•Ca3Al2O6 reduced CO2 diffusion resistance and gave sorbents high absorptivity.•The cyclic ...sorption stability is due to the small original surface free energy.
CaO-based CO2 sorbents play a significant role in sorption enhanced methane steam reforming process for hydrogen production and CO2 emission reduction. However, the sorbents suffer from decreasing CO2 sorption capacity and stability due to the sintering of CaO grains. In this study, we modified CaO sorbents by incorporating Al to obtain CaO/Ca3Al2O6 sorbents via a modified sol-gel method. CO2 sorption evaluation shows that the relative quantity of CaO to Al2O3 plays an overwhelming role in the CO2 sorption capacity and stability of the CaO/Ca3Al2O6 sorbents. Superior CO2 sorption ratio (51.92% for sorbent C8A2 at 500°C) is achieved, which is 5 times higher than that of the as-synthesized pure CaO sorbent. The high CO2 sorption ratio is due to the existence of inert Ca3Al2O6, which decreases the diffusion resistance of CO2 through product layer during the carbonation reaction. Meanwhile, the superior CO2 cyclic sorption stability is ascribed to the small original surface free energy of the as-synthesized sorbents.
The tyrosine kinase inhibitor (TKI) gefitinib exerts good therapeutic effect on NSCLC patients with sensitive EGFR-activating mutations. However, most patients ultimately relapse due to the ...development of drug resistance after 6–12 months of treatment. Here, we showed that a HIF-1α inhibitor, YC-1, potentiated the antitumor efficacy of gefitinib by promoting EGFR degradation in a panel of human NSCLC cells with wild-type or mutant EGFRs. YC-1 alone had little effect on NSCLC cell survival but significantly enhanced the antigrowth and proapoptotic effects of gefitinib. In insensitive NSCLC cell lines, gefitinib efficiently inhibited the phosphorylation of EGFR but not the downstream signaling of ERK, AKT and STAT3; however, when combined with YC-1 treatment, these signaling pathways were strongly impaired. Gefitinib treatment induced EGFR arrest in the early endosome, and YC-1 treatment promoted delayed EGFR transport into the late endosome as well as receptor degradation. Moreover, the YC-1-induced reduction of HIF-1α protein was associated with the enhancement of EGFR degradation. HIF-1α knockdown promoted EGFR degradation, showing synergistic antigrowth and proapoptotic effects similar to those of the gefitinib and YC-1 combination treatment in NSCLC cells. Our findings provide a novel combination treatment strategy with gefitinib and YC-1 to extend the usage of gefitinib and overcome gefitinib resistance in NSCLC patients.
The intestinal flora has become very active in studies related to Parkinson's disease (PD) in recent years. The microbe‐gut‐brain axis is closely related to the maintenance of brain homeostasis as ...well as PD pathogenesis. Alterations in gut bacteria can contribute to neuroinflammation and dopamine (DA) neurodegeneration. Lactobacillus murinus, a gram‐positive bacterium, is a commensal gut bacteria present in the mammalian gut and considered as a potential probiotic due to its beneficial effects, including anti‐inflammatory and antibacterial actions. In this study, the effects of live L. murinus and heat‐killed L. murinus on DA neuronal damage in rats and the underlying mechanisms were investigated. Data showed that heat‐killed L. murinus ameliorated 6‐hydroxydopamine‐induced motor dysfunctions and loss of substantia nigra DA neurons, while no protection was shown in live L. murinus treatment. At the same time, heat‐killed L. murinus reduced the activation of NLRP3 inflammasome in microglia and the secretion of pro‐inflammatory factors, thus inhibiting the development of neuroinflammation. Furthermore, heat‐killed L. murinus failed to display its original neuroprotective properties in NLRP3 inflammasome knockout mice. Together, heat‐killed L. murinus conferred neuroprotection against DA neuronal loss via the inhibition of microglial NLRP3 inflammasome activation. These findings provide a promising potential for future applications of L. murinus, and also beneficial strategy for PD treatment.
Neuroinflammation plays a crucial role in the pathological process of Parkinson’s disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the ...process of neuroinflammation. Activation of the NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasome activation could be an important breakthrough point on PD therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts, and other plant tissues with anti-inflammatory, antioxidant, and neuroprotective properties. However, the mechanisms underlying EA-mediated anti-inflammation and neuroprotection have not been fully elucidated. In this study, a lipopolysaccharide- (LPS-) induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. In addition, the DA neuronal MN9D cell line and microglial BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism. Results indicated that EA ameliorated LPS-induced DA neuronal loss in the rat substantia nigra. Further, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and subsequent proinflammatory cytokines’ excretion. Second, EA-mediated antineuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity were not shown upon microglial NLRP3 siRNA treatment. In conclusion, this study demonstrated that EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome activation.
A series of ordered mesoporous carbons loaded with different contents of NiCo2O4 (X-NiCo2O4/OMC) were synthesized via a facile hydrothermal method and proposed as a catalyst for electrocarboxylation ...of benzophenone for the first time. The materials were characterized by many measurements, which showed mesoporous structures with high surface area, good dispersion and stability. What's more, the materials exhibit good electrocatalytic performance due to its good ability to capture CO2 and accelerate reaction rate, which brought by redox couples (Ni3+/Ni2+, Co3+/Co2+) and vacancy defects of NiCo2O4. The optimal yield of methyl benzilate reaches 86% on 3-NiCo2O4/OMC.
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•The use of NiCo2O4/OMC cathodes in electrocarboxylation of benzophenone with CO2 was investigated for the first time.•The yield of methyl benzilate reaches 86% on optimal NiCo2O4/OMC material and electrolysis conditions.•The high-performance mainly results from the redox couples and vacancy defects of NiCo2O4/OMC.
Chiral phosphoric acid-catalyzed asymmetric aldehyde prenylation has been established using an α,α-dimethyl allyl boronic ester. The transformation provides expedient access to a wide array of aryl, ...heteroaryl, aryl-substituted alkenyl and primary and secondary aliphatic homoprenyl alcohols with excellent asymmetric induction. The utility of this asymmetric catalysis strategy has been demonstrated through a short and efficient total synthesis of the two natural products (−)-rosiridol and (−)-bifurcadiol.
An asymmetric aldehyde prenylation method assisted by a (
R
)-BINOL-derived phosphoric acid (
R
)-TRIP catalyst for the total synthesis of (−)-rosiridol and (−)-bifurcadiol has been reported.
Mesoporous silver materials are used as electrocatalysts for halogenated compounds. The mesoporous silver materials have uniform mesoporous size (8 nm), large specific surface area (12 m
2
g
−1
), ...high pore volume (0.07 cm
3
g
−1
), and a good 3D network structure of the metallic silver skeleton. The results show that the prepared materials exhibit high performance in electrocatalytic carboxylation of halogenated compounds to acid (78%).
Mesoporous silver materials are used as electrocatalysts for halogenated compounds and exhibit high performance in electrocatalytic carboxylation of halogenated compounds to carboxylic acid (78%).
Abstract
We developed a convolutional neural network model to distinguish the double-lined spectroscopic binaries (SB2s) from others based on single-exposure medium-resolution spectra (
R
∼ 7500). ...The training set consists of a large set of mock spectra of single stars and binaries synthesized based on the MIST stellar evolutionary model and ATLAS9 atmospheric model. Our model reaches a novel theoretic false-positive rate by adding a proper penalty on the negative sample (e.g., 0.12% and 0.16% for the blue/red arm when the penalty parameter Λ = 16). Tests show that the performance is as expected and favors FGK-type main-sequence (MS) binaries with high mass ratio (
q
≥ 0.7) and large radial velocity separation (Δ
v
≥ 50 km s
−1
). Although the real false-positive rate cannot be estimated reliably, validating on eclipsing binaries identified from Kepler light curves indicates that our model predicts low binary probabilities at eclipsing phases (0, 0.5, and 1.0) as expected. The color–magnitude diagram also helps illustrate its feasibility and capability of identifying FGK MS binaries from spectra. We conclude that this model is reasonably reliable and can provide an automatic approach to identify SB2s with period ≲10 days. This work yields a catalog of binary probabilities for over 5 million spectra of 1 million sources from the LAMOST medium-resolution survey (MRS) and a catalog of 2198 SB2 candidates whose physical properties will be analyzed in a follow-up paper. Data products are made publicly available online, as well as our Github website.
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