In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model of HepG2 ...cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate the expression of phospho-AMP-activated protein kinase (
-AMPK) proteins to inhibit the expression of the sterol regulatory element binding protein-1c (SREBP-1c) proteins on increasing lipid synthesis and up-regulating the expression of the PPAP-α and CPT-1 proteins on promoting the β-oxidation of fatty acids. Moreover, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) can significantly inhibit reactive oxygen species' (ROS) production, promote the activities of intracellular antioxidases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; and catalase, CAT) and bring down the content of malondialdehyde (MDA) derived from lipid peroxidation. Further investigations revealed that the regulation of these five oligopeptides on oxidative stress was achieved through activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to raise the expression levels of the heme oxygenase 1 (HO-1) protein and downstream antioxidant proteases. Therefore, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) could serve as candidate ingredients to develop functional products for treating NAFLD.
Mitochondrial antiviral-signaling protein (MAVS) transmits signals from RIG-I-like receptors after RNA virus infections. However, the mechanism by which MAVS activates downstream components, such as ...TBK1 and IKKα/β, is unclear, although previous work suggests the involvement of NEMO or TBK1-binding proteins TANK, NAP1, and SINTBAD. Here, we report that MAVS-mediated innate immune activation is dependent on TRAFs, partially on NEMO, but not on TBK1-binding proteins. MAVS recruited TBK1/IKKε by TRAFs that were pre-associated with TBK1/IKKε via direct interaction between the coiled-coil domain of TRAFs and the SDD domain of TBK1/IKKε. TRAF2-/-3-/-5-/-6-/- cells completely lost RNA virus responses. TRAFs' E3 ligase activity was required for NEMO activation by synthesizing ubiquitin chains that bound to NEMO for NF-κB and TBK1/IKKε activation. NEMO-activated IKKα/β were important for TBK1/IKKε activation through IKKα/β-mediated TBK1/IKKε phosphorylation. Moreover, individual TRAFs differently mediated TBK1/IKKε activation and thus fine-tuned antiviral immunity under physiological conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is well known that abscisic acid (ABA)-induced leaf senescence and premature leaf senescence negatively affect the yield of rice (Oryza sativa). However, the molecular mechanism underlying this ...relationship, especially the upstream transcriptional network that modulates ABA level during leaf senescence, remains largely unknown. Here, we demonstrate a rice NAC transcription factor, OsNAC2, that participates in ABA-induced leaf senescence. Overexpression of OsNAC2 dramatically accelerated leaf senescence, whereas its knockdown lines showed a delay in leaf senescence. Chromatin immunoprecipitation-quantitative PCR, dual-luciferase, and yeast one-hybrid assays demonstrated that OsNAC2 directly activates expression of chlorophyll degradation genes, OsSGR and OsNYC3. Moreover, ectopic expression of OsNAC2 leads to an increase in ABA levels via directly up-regulating expression of ABA biosynthetic genes (OsNCED3 and OsZEP1) as well as down-regulating the ABA catabolic gene (OsABA8ox1). Interestingly, OsNAC2 is upregulated by a lower level of ABA but downregulated by a higher level of ABA, indicating a feedback repression of OsNAC2 by ABA. Additionally, reduced OsNAC2 expression leads to about 10% increase in the grain yield of RNAi lines. The novel ABA-NAC-SAGs regulatory module might provide a new insight into the molecular action of ABA to enhance leaf senescence and elucidates the transcriptional network of ABA production during leaf senescence in rice.
Plants can perceive environmental changes and respond to external stressors. Here, we show that OsNAC2, a member of the NAC transcription factor family, was strongly induced by ABA and osmotic ...stressors such as drought and high salt. With reduced yields under drought conditions at the flowering stage, OsNAC2 overexpression lines had lower resistance to high salt and drought conditions. RNAi plants showed enhanced tolerance to high salinity and drought stress at both the vegetative and flowering stages. Furthermore, RNAi plants had improved yields after drought stress. A microarray assay indicated that many ABA-dependent stress-related genes were down-regulated in OsNAC2 overexpression lines. We further confirmed that OsNAC2 directly binds the promoters of LATE EMBRYOGENESIS ABUNDANT 3 (OsLEA3) and Stress-Activated Protein Kinases 1 (OsSAPK1), two marker genes in the abiotic stress and ABA response pathways, respectively. Our results suggest that in rice OsNAC2 regulates both abiotic stress responses and ABA-mediated responses, and acts at the junction between the ABA and abiotic stress pathways.
Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD). As the most common means to detect SAD, spirometry needs good cooperation ...and its reliability is controversial. Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity. We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF.
The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed. ROC curves of IOS to detect SAD were analyzed.
209 subjects with chronic respiratory symptoms and PPF were included. Subjects who reported sputum had higher R5-R20 and Fres than those who didn't. Subjects with dyspnea had higher R5, R5-R20 and AX than those without. CAT and mMRC scores correlated better with IOS parameters than with spirometry. R5, R5-R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without. Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5-R20, 0.30 kPa/L for AX and 11.23 Hz for Fres. Fres has the largest AUC (0.665, P = 0.001) among these parameters. Compared with spirometry, prevalence of SAD was higher when measured with IOS. R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002).
IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms. IOS could be an additional method for SAD detection in the early stage of diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Plant development and adaptation to environmental stresses are intimately associated with programmed cell death (PCD). Although some of the mechanisms regulating PCD e.g., accumulation of ...reactive oxygen species (ROS) are common among responses to different abiotic stresses, the pathways mediating salt‐induced PCD remain largely uncharacterized. Here we report that overexpression of OsNAC2, which encodes a plant‐specific transcription factor, promotes salt‐induced cell death accompanied by the loss of plasma membrane integrity, nuclear DNA fragmentation, and changes to caspase‐like activity. In OsNAC2‐knockdown lines, cell death was markedly decreased in response to severe salt stress. Additionally, OsNAC2 expression was enhanced in rice seedlings exposed to a high NaCl concentration. Moreover, the results of quantitative real‐time PCR, chromatin immunoprecipitation, dual‐luciferase, and yeast one‐hybrid assays indicated that OsNAC2 targeted genes that encoded an ROS scavenger (OsCOX11) and a caspase‐like protease (OsAP37). Furthermore, K+‐efflux channels (OsGORK and OsSKOR) were clearly activated by OsNAC2. Overall, our results suggested that OsNAC2 accelerates NaCl‐induced PCD and provide new insights into the mechanisms that affect ROS accumulation, plant caspase‐like activity, and K+ efflux.
Significance Statement
We have uncovered a previously unknown molecular pathway regulating salt‐induced PCD in plants. Our findings also provide clues regarding the possible roles of NAC TFs during stress‐induced PCD across diverse plant species.
Four new dimeric sorbicillinoids (
-
and
) and a new monomeric sorbicillinoid (
) as well as six known analogs (
-
) were purified from the fungal strain
H8, which was obtained from mangrove ...sediment, and showed potent inhibitory activity against the tea pathogenic fungus
(
). The planar structures of
-
were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus
. Compounds
,
,
,
, and
exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED
of 24.25 ± 1.57 µg/mL. The ED
values of compounds
,
,
,
, and
were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds
and
, which imparted toxic effects on zebrafish even at 0.625 μM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (
,
, and
) from
H8 displayed low toxicity and high anti-tea pathogenic fungus potential.
HER2-low breast cancer (BC) has a poor prognosis, making the development of more suitable treatment an unmet clinical need. While chemotherapy is the main method of treatment for HER2-low BC, not all ...patients benefit from it. Antineoplastic therapy without chemotherapy has shown promise in clinical trials and is being explored further. As quantitative detection techniques become more advanced, they assist in better defining the expression level of HER2 and in guiding the development of targeted therapies, which include directly targeting HER2 receptors on the cell surface, targeting HER2-related intracellular signaling pathways and targeting the immune microenvironment. A new anti-HER2 antibody-drug conjugate called T-DM1 has been successfully tested and found to be highly effective in clinical trials. With this progress, it could eventually be transformed from a disease without a defined therapeutic target into a disease with a defined therapeutic molecular target. Furthermore, efforts are being made to compare the sequencing and combination of chemotherapy, endocrine therapy, and HER2-targeted therapy to improve prognosis to customize the subtype of HER2 low expression precision treatment regimens. In this review, we summarize the current and upcoming treatment strategies, to achieve accurate management of HER2-low BC.
This article investigates the predefined-time stabilization problems of Takagi-Sugeno (T-S) fuzzy systems. For addressing the considered problems, a class of novel integral sliding mode surface is ...first designed based on the time-regulator function, on which the system states are forced to converge to the origin in a predefined time after the sliding mode surface is reached. Further, the proposed sliding surface is employed to construct predefined-time integral sliding mode controller for the time delayed and disturbed T-S fuzzy system. The settling time appears as the sum of two predefined-time parameters in the controller design, which, respectively, adjusts the convergence time for reaching the sliding mode surface and the convergence time for arriving the origin from the sliding mode surface. The sufficient conditions for maintaining the predefined-time stability of the T-S fuzzy systems are obtained through systematic Lyapunov stability analysis. Finally, a numerical simulation example on delayed and disturbed Chua circuit is presented to verify the effectiveness of the proposed predefined-time integral sliding mode controller.
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