Litchi (
) is an economically important fruit tree in southern China and is widely cultivated in subtropical regions. However, irregular flowering attributed to inadequate floral induction leads to a ...seriously fluctuating bearing. Litchi floral initiation is largely determined by cold temperatures, whereas the underlying molecular mechanisms have yet to be identified. In this study, we identified four
(
) homologs in litchi, of which
,
and
showed a decrease in response to the floral inductive cold. A similar expression pattern was observed for the
homolog (
) in litchi. Furthermore, both LcCBF2 and LcCBF3 were found to bind to the promoter of
to activate its expression, as indicated by the analysis of yeast-one-hybrid (Y1H), electrophoretic mobility shift assays (EMSA), and dual luciferase complementation assays. Ectopic overexpression of
and
in
caused delayed flowering and increased freezing and drought tolerance, whereas overexpression of
in
had no significant effect on flowering time. Taken together, we identified LcCBF2 and LcCBF3 as upstream activators of
and proposed the contribution of the cold-responsive CBF to the fine-tuning of flowering time.
Human adenovirus (HAdV) infection is common and can develop to serious conditions with high mortality, yet the mechanism of HAdV infection remains unclear. In the present study, the serum metabolite ...profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection (URTI) were explored.
In total, 35 patients were enrolled in the study following an outbreak of HAdV-7 in the army, of whom 14 had pneumonia and 21 had URTI. Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.
Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules, including glycerophospholipids, fatty acyls, and sphingolipids. The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways, including sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients, but not between the acute and recovery stages for the URTI patients. Ceramide and lactosylceramide, involved in sphingolipid metabolism, were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities area under curve (AUC) 0.742 and 0.716, respectively; combination AUC 0.801.
Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia, especially the sphingolipid metabolism involving ceramide and lactosylceramide, which might thus be a potential intervention target in the treatment of HAdV infection.
Background Amending from ancient classic, Ziyin Tongluo Formula (ZYTLF) has been prescribed to treat postmenopausal osteoporosis (PMOP) for decades with good curative effect. However, the possible ...mechanisms of it are still unknown. Methods Ovariectomized rat model was established to validate the therapeutic effect of ZYTLF on PMOP by Micro-CT bone analysis and pathological observation. Subsequently, active ingredients of ZYTLF and corresponding putative targets were identified by online databases. Overlapping genes were first obtained from mining genes associated with PMOP and then overlapped them with the putative targets. Key genes were selected from the multiple constructed and analyzed networks. GO and KEGG pathway enrichment analysis were performed by importing the key genes to the DAVID database. Moreover, validation of the binding association between key targets and their corresponding active compounds were accomplished by AutoDock Tools and other software. Lastly, Enzyme linked immunosorbent assay (Elisa) detection and Western blot analysis were utilized to further explore the possible mechanism of ZYTLF on PMOP. Results With 129 target genes interacting with PMOP, 92 active compounds of ZYTLF corresponded to 243 targets, and 50 key genes were chosen. Network analysis revealed the top 10 active ingredients, such as quercetin and kaempferol and the top 50 key genes, such as ERalpha, p38 MAPK, p-AKT and TGF-beta1. Enrichment analysis uncovered multiple signaling pathways, including estrogen signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Furthermore, our finding of the foremost active compounds was tightly bound to the core proteins, which were verified by molecular docking analysis. Through experimental studies, we confirmed that the prescription of ZYTLF could ameliorate the OVX-induced bone loss, suppress the osteoclast activity and boost osteoblast ability through experimental studies. Conclusion The potential mechanisms and therapeutic effects of ZYTLF against PMOP may be ascribed to inhibition of osteoclast activity, boost of osteoblast activity and enhancement of the expression of ERalpha. Keywords: Postmenopausal osteoporosis, Ziyin Tongluo Formula, Traditional Chinese medicine, Ovariectomy, Network pharmacology, Molecular docking
The doping of ZnO is efficient to improve the piezoelectric property and thermal stability of Pb(Mg1/3Nb2/3)O3–PbTiO3 (PMN–PT) based ceramics. However, the underlying physics, especially the local ...domain structures of the ZnO modified PMN–PT ceramics, which is strongly associated with the electric properties, is not clear yet. In this paper, we investigated the local domain structures and their evolution as a function of x in PMN–0.32PT:xZnO ceramics. It was found that, the domain evolution is mainly caused by the growth of grain size induced by the sintering aiding effect of ZnO at x < 0.04, and the domain evolution can be attributed to the phase transition induced by the partial replacement of Mg2+ by Zn2+ in the B‐site of PMN–PT lattice at x > 0.06. Furthermore, we also investigated the domain structure evolution as functions of temperature and local external electric field in PMN–0.32PT:0.06ZnO ceramics, which exhibited superior piezoelectric property relative to other compositions. We found that the irregular nanodomains are more stable at high‐temperature range, and the regular non‐180° domains exhibited more complex rotation behavior under local electric field, which probably leads to the thermal stability and piezoelectric property enhancement in the ZnO‐modified PMN–0.32PT ceramics.
PRDM (PRDI‐BF1 and RIZ domain‐containing) proteins constitute a family of zinc finger proteins and play important roles in multiple cellular processes by acting as epigenetic modifiers. PRDM5 is a ...recently identified member of the PRDM family and may function as a tumor suppressor in several types of cancer. However, the role of PRDM5 in murine melanoma remains largely unknown. In our study, effect of PRDM5 on murine melanoma cells was determined and results showed that PRDM5 overexpression significantly promoted proliferation, migration, and invasion of murine melanoma B16F10 cells. Consistently, silencing of PRDM5 expression significantly inhibited proliferation, invasion, and migration of B16F10 cells. In vivo study also showed that PRDM5 silencing significantly inhibited the growth and metastasis of melanoma in mice. PRDM5 was then found to increase the expression and activation of JNK in B16F10 cells. JNK silencing significantly reduced PRDM5‐mediated up‐regulation of JNK expression and blocked the PRDM5‐induced proliferation and invasion of B16F10 cells. To further verify the involvement of JNK signaling in PRDM5‐induced progression of B16F10 cells, a specific JNK inhibitor was employed to inhibit the JNK signaling pathway, and results showed that PRDM5‐induced proliferation and invasion of B16F10 cells were abolished. We conclude that PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression and strategies targeting PRDM5 may be promising for the therapy of melanoma.
We conclude that PRDM5 promotes the proliferation and invasion of murine melanoma cells through up‐regulating JNK expression. Our findings suggest that strategies targeting PRDM5 may be promising for the therapy of melanoma.
The lacewing, Chrysoperla sinica, is an important predatory insect, which plays an important role in the integrated pest management of agroforestry pests. However, the extensive use of insecticides ...negatively affects C. sinica. The acute toxicity, risk level, and, sublethal effects on growth and production, predation ability, protective enzyme activity and genotoxicity of four insecticides: indoxacarb, emamectin benzoate, imidacloprid and lambda-cyhalothrin to C. sinica were studied. The results showed that all four insecticides had lethal toxicity to larvae of C. sinica. Among them, emamectin benzoate had the highest toxicity with LC50 value of 7.41 mg/L. The insecticides also had different effects on the growth and reproduction of C. sinica, of which lambda-cyhalothrin had the greatest impacts. Even at a very low LC1 concentration (3.37 mg/L), it had strong impacts on the growth, reproduction and predatory ability of C. sinica. The four insecticides also caused a decrease in the predatory ability of the lacewing, of which lambda-cyhalothrin had the greatest effect. During the larval stage, the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were significantly decreased by the four insecticides. At the pupal and adult stages, the effects of the four insecticides on the activities of protective enzymes were different, and the activities of SOD, CAT and POD decreased or increased. Indoxacarb and lambda-cyhalothrin exposure induced DNA damage in the haemocytes of C. sinica and produced obvious genotoxicity. These results provide important scientific basis for the rational use of these insecticides and the protection and utilization of lacewing.
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•Emamectin benzoate has a high acute toxicity on the larvae of lacewing.•Lambda-cyhalothrin has serious sublethal effects on the different stages of lacewing.•Decreased the predatory ability, impacted the activities of protective enzymes and induced DNA damage in lacewing.
During the clamping process in an injection-molding machine, the mold’s movement is directly driven by the velocity of the crosshead. The form of the adjustment on the crosshead’s kinematics can ...influence the final dynamics of the mold, which can contribute to the stability of the clamping duration further. This article is aimed at investigating the kinematics analysis and the stability management strategy of the mold in the early design stage for the clamping mechanism. The two different velocity-controlled forms of the crosshead, constant and variable kinematics adjustments, are applied and compared in the clamping analysis. Three factors of the crosshead, the maximum velocity, the acceleration/deceleration stage adjustment, and the multi acceleration/deceleration process, are validated for the stability control of the mold’s motion in the injection molding process. The results show an extra “fast” process is detected in the constant condition when compared to the variable crosshead’s kinematics adjustment. Furthermore, by the reasonable adjustment of the maximum velocity and two special positions of the crosshead during the acceleration and deceleration stages, the maximum acceleration fluctuation of the mold is decreased by more than 50%, allowing the mold to move more steadily.
Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti‐cancer efficacy and acquired ...drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi‐kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis‐related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c‐Kit), mitosis‐related kinase Aurora B and chronic inflammation‐related kinase CSF‐1R in a high potency manner with the IC50 at a single‐digit nanomolar range. Consequently, CS2164 displayed anti‐angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand‐dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B‐mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF‐1R phosphorylation that led to the suppression of ligand‐stimulated monocyte‐to‐macrophage differentiation and reduced CSF‐1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well‐tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi‐kinase inhibitor with potent anti‐tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.
In this paper, we designed, discovered, and evaluated a novel orally active multi‐kinase inhibitor, CS2164, which simultaneously inhibits the angiogenesis‐related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFR‐alpha, and c‐Kit), mitosis‐related kinase Aurora B, and chronic inflammatory‐related kinase CSF‐1R in a high potency manner with the IC50 at a single digital nanomolar range. Through both in vitro cell based studies and in vivo animal xenograft models, we provide solid preclinical evidence for the potent anti‐tumor efficacy of CS2164.
Acute lung injury (ALI) is a serious inflammatory disease with clinical manifestations of hypoxemia and respiratory failure. Presently, there is no effective treatment of ALI. Although emodin from
L. ...exerts anti-ALI properties, the underlying mechanisms have not been fully explored.
This study aimed to investigate the therapeutic effect and mechanism of emodin on LPS-induced ALI in mice.
RAW264.7 cells and zebrafish larvae were stimulated by LPS to establish inflammatory models. The anti-inflammatory effect of emodin was assessed by ELISA, flow cytometric analysis, and survival analysis.
mechanisms were explored by using Western blotting, luciferase assay, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) approach. The acute lung injury model in mice was established by the intratracheal administration of LPS, and the underlying mechanisms were assessed by detecting changes in histopathological and inflammatory markers and Western blotting in lung tissues.
Emodin inhibited the inflammatory factor production and oxidative stress in RAW264.7 cells, and prolonged the survival of zebrafish larvae after LPS stimulation. Emodin suppressed the expression levels of phosphorylated JNK at Thr183/tyr182 and phosphorylated Nur77 at Ser351 and c-Jun, and increased the expression level of Nur77 in LPS-stimulated RAW264.7 cells, while these regulatory effects of emodin on Nur77/c-Jun were counteracted by JNK activators. The overexpression of JNK dampened the emodin-mediated increase in Nur77 luciferase activity and Nur77 expression. Moreover, the inhibitory effect of emodin on c-Jun can be attenuated by Nur77 siRNA. Furthermore, emodin alleviated LPS-induced ALI in mice through the regulation of the JNK/Nur77/c-Jun pathway.
Emodin protects against LPS-induced ALI through regulation on JNK/Nur77/c-Jun signaling. Our results indicate the potential of emodin in the treatment of ALI.
The simultaneous increases in blood lactic acid and erythrocytes after intense exercise could suggest a link between lactate and the erythropoiesis. However, the effects of lactic acid on ...erythropoiesis remain to be elucidated. Here, we utilized a mouse model to determine the role of lactic acid in this process in parallel with studies using leukaemic K562 cells. Treatment of K562 cells in vitro with lactic acid increased the mRNA and protein expression of haemoglobin genes and the frequency of GPA
cells. Also, increases in haematocrit and CD71
/Ter119
erythroid cells were observed in lactic acid-treated mice, which showed a physiological increase in blood lactate. Mouse bone marrow CD34
/CD117
cells showed an increase in erythroid burst-forming units after stimulation with lactic acid in vitro. Furthermore, lactic acid increased the intracellular reactive oxygen species (ROS) content in bone marrow and in K562 cells. Erythroid differentiation induced in Haematopoietic Stem Cells (HSCs) and K562 cells by lactic acid was abolished by reducing ROS levels with SOD or 2-mercaptoethanol, which suggests that ROS is a critical regulator of this process. These findings provide a better understanding of the role of lactic acid in cellular metabolism and physiological functions.
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