Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. ...Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.
Lysine specific demethylase 1 (LSD1) and Histone deacetylases (HDACs) are promising drug targets for cancers. Recent studies reveal an important functional interplay between LSD1 and HDACs, and there ...is evidence for the synergistic effect of combined LSD1 and HDAC inhibitors on cancers. Therefore, development of inhibitors targeting both LSD1 and HDACs might be a promising strategy for epigenetic therapy of cancers. We report herein the synthesis of a series of tranylcypromine derivatives as LSD1/HDACs dual inhibitors. Most compounds showed potent LSD1 and HDACs inhibitory activity, especially compound 7 displayed the most potent inhibitory activity against HDAC1 and HDAC2 with IC50 of 15 nM and 23 nM, as well as potent inhibition against LSD1 with IC50 of 1.20 μM. Compound 7 demonstrated stronger anti-proliferative activities than SAHA with IC50 values ranging from 0.81 to 4.28 μM against MGC-803, MCF-7, SW-620 and A-549 human cancer cell lines. Further mechanistic studies showed that compound 7 treatment in MGC-803 cells dose-dependently increased cellular H3K4 and H3K9 methylation, as well as H3 acetylation, decreased the mitochondrial membrane potential and induced remarkable apoptosis. Docking studies showed that compound 7 can be well docked into the active binding sites of LSD1 and HDAC2. This finding highlights the potential for the development of LSD1/HDACs dual inhibitors as novel anticancer drugs.
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•A series of tranylcypromine derivatives were discovered as novel LSD1/HDACs dual inhibitors.•Compound 7 exhibited potent dual LSD1/HDACs inhibition with strong antiproliferative activity.•Compound 7 dose-dependently increased cellular H3K4 and H3K9 methylation, as well as H3 acetylation.•Compounds 7 induced remarkable apoptosis and decreased mitochondrial membrane potential.
Elm (Ulmus) has a long history of use as a high-quality heavy hardwood famous for its resistance to drought, cold, and salt. It grows in temperate, warm temperate, and subtropical regions. This is ...the first report of Ulmaceae chloroplast genomes by de novo sequencing. The Ulmus chloroplast genomes exhibited a typical quadripartite structure with two single-copy regions (long single copy LSC and short single copy SSC sections) separated by a pair of inverted repeats (IRs). The lengths of the chloroplast genomes from five Ulmus ranged from 158,953 to 159,453 bp, with the largest observed in Ulmus davidiana and the smallest in Ulmus laciniata. The genomes contained 137-145 protein-coding genes, of which Ulmus davidiana var. japonica and U. davidiana had the most and U. pumila had the fewest. The five Ulmus species exhibited different evolutionary routes, as some genes had been lost. In total, 18 genes contained introns, 13 of which (trnL-TAA+, trnL-TAA-, rpoC1-, rpl2-, ndhA-, ycf1, rps12-, rps12+, trnA-TGC+, trnA-TGC-, trnV-TAC-, trnI-GAT+, and trnI-GAT) were shared among all five species. The intron of ycf1 was the longest (5,675bp) while that of trnF-AAA was the smallest (53bp). All Ulmus species except U. davidiana exhibited the same degree of amplification in the IR region. To determine the phylogenetic positions of the Ulmus species, we performed phylogenetic analyses using common protein-coding genes in chloroplast sequences of 42 other species published in NCBI. The cluster results showed the closest plants to Ulmaceae were Moraceae and Cannabaceae, followed by Rosaceae. Ulmaceae and Moraceae both belonged to Urticales, and the chloroplast genome clustering results were consistent with their traditional taxonomy. The results strongly supported the position of Ulmaceae as a member of the order Urticales. In addition, we found a potential error in the traditional taxonomies of U. davidiana and U. davidiana var. japonica, which should be confirmed with a further analysis of their nuclear genomes. This study is the first report on Ulmus chloroplast genomes, which has significance for understanding photosynthesis, evolution, and chloroplast transgenic engineering.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are significant components in the MAPK signal pathway and play essential roles in regulating plants against drought stress. To explore MAPKKK ...gene family functioning in cotton response and resistance to drought stress, we conducted a systematic analysis of GhMAPKKKs.
In this study, 157 nonredundant GhMAPKKKs (including 87 RAFs, 46 MEKKs and 24 ZIKs) were identified in cotton (Gossypium hirsutum). These GhMAPKKK genes are unevenly distributed on 26 chromosomes, and segmental duplication is the major way for the enlargement of MAPKKK family. Furthermore, members within the same subfamily share a similar gene structure and motif composition. A lot of cis-elements relevant to plant growth and response to stresses are distributed in promoter regions of GhMAPKKKs. Additionally, these GhMAPKKKs show differential expression patterns in cotton tissues. The transcription levels of most genes were markedly altered in cotton under heat, cold and PEG treatments, while the expressions of some GhMAPKKKs were induced in cotton under drought stress. Among these drought-induced genes, we selected GhRAF4 and GhMEKK12 for further functional characterization by virus-induced gene silencing (VIGS) method. The experimental results indicated that the gene-silenced cotton displayed decreased tolerance to drought stress. Malondialdehyde (MDA) content was higher, but proline accumulation, relative leaf water content and activities of superoxide dismutase (SOD) and peroxidase (POD) were lower in the gene-silenced cotton, compared with those in the controls, under drought stress.
Collectively, a systematic survey of gene structure, chromosomal location, motif composition and evolutionary relationship of MAPKKKs were performed in upland cotton (Gossypium hirsutum). The following expression and functional study showed that some of them take important parts in cotton drought tolerance. Thus, the data presented here may provide a foundation for further investigating the roles of GhMAPKKKs in cotton response and resistance to drought stress.
Background and Purpose- Ischemic stroke impairs endoplasmic reticulum (ER) function, causes ER stress, and activates the unfolded protein response. The unfolded protein response consists of 3 ...branches controlled by ER stress sensor proteins, which include PERK (protein kinase RNA-like ER kinase). Activated PERK phosphorylates eIF2α (eukaryotic initiation factor 2 alpha), resulting in inhibition of global protein synthesis. Here, we aimed to clarify the role of the PERK unfolded protein response branch in stroke. Methods- Neuron-specific and tamoxifen-inducible PERK conditional knockout (cKO) mice were generated by cross-breeding Camk2a-CreERT2 with
mice. Transient middle cerebral artery occlusion was used to induce stroke. Short- and long-term stroke outcomes were evaluated. Protein synthesis in the brain was assessed using a surface-sensing-of-translation approach. Results- After tamoxifen-induced deletion of
in forebrain neurons was confirmed in PERK-cKO mice, PERK-cKO and control mice were subjected to transient middle cerebral artery occlusion and 3 days or 3 weeks recovery. PERK-cKO mice had larger infarcts and worse neurological outcomes compared with control mice, suggesting that PERK-induced eIF2α phosphorylation and subsequent suppression of translation protects neurons from ischemic stress. Indeed, better stroke outcomes were observed in PERK-cKO mice that received postischemic treatment with salubrinal, which can restore the ischemia-induced increase in phosphorylated eIF2α in these mice. Finally, our data showed that post-treatment with salubrinal improved functional recovery after stroke. Conclusions- Here, we presented the first evidence that postischemic suppression of translation induced by PERK activation promotes recovery of neurological function after stroke. This confirms and further extends our previous observations that recovery of ER function impaired by ischemic stress critically contributes to stroke outcome. Therefore, future research should include strategies to improve stroke outcome by targeting unfolded protein response branches to restore protein homeostasis in neurons.
In this work, we grew hierarchical Ni3N/Ni0.2Mo0.8N heterostructure microspheres on 3D NF, Ni3N/Ni0.2Mo0.8N/NF, which displays robust and high-performance catalytic activities for both water and urea ...electrolysis.
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•The hierarchical Ni3N/Ni0.2Mo0.8N heterostructure nanorods arrays were prepared.•The obtained material shows great trifunctional catalytic performances.•For both water and urea electrolysis, lower cell voltages are required.•Metallic states, synergistic effect and hierarchical structure work together.
The energy-saving urea electrolysis integrating the HER and smart urea oxidation reaction (UOR) can supplant the kinetics-restricted oxygen evolution reaction (OER) for hydrogen generation, but is still severely thwarted by poor electrocatalysts. Herein, a tractable hydrothermal protocol coupled with subsequent nitridation is found to enable uniform growth of the Ni3N/Ni0.2Mo0.8N heterostructure microspheres assembled by the uniform nanorod arrays on the nickel foam framework (Ni3N/Ni0.2Mo0.8N/NF). The as-obtained Ni3N/Ni0.2Mo0.8N/NF catalyst exhibits multifunctional superior performance for both overall water and urea electrolysis. For HER, the low overpotentials of 55 and 65 mV can be only required to deliver 10 mA cm−2 in alkaline and neutral electrolytes, respectively. Furthermore, for UOR a ultrasmall potential of 1.328 V (vs. RHE) at 10 mA cm−2 occurs, which is much lower than that required for OER process. When applying the Ni3N/Ni0.2Mo0.8N/NF as anode for OER and cathode for HER, the water electrolyzer requires low cell voltages of 1.487 and 1.724 V to achieve 10 and 200 mA cm−2, respectively. More significantly, the urea electrolyser presents ultralow cell voltages of 1.348 and 1.514 V at 10 and 200 mA cm−2 and remarkable longevity for over 500 h. Such impressive performances exceed most reported noble-metal-free catalysts and even vie for the benchmarking noble metal catalysts, heralding its tremendous utilitarian prospects for the cost-effective and energy-saving hydrogen generation.
Laboratory experiments were carried out to determine the long-term effects of N-acyl-homoserine lactone (AHL)-based quorum sensing on the characteristics of ANAMMOX granules in high-loaded reactors. ...Results clearly showed that adding 30 mg L−1 N-octanoyl-DL-homoserinelactone (C8-HSL) at the initial stage (1–40 d) of the experiment had long-term positive effects on the settleability of granules and controlled the sludge floatation effectively. C8-HSL decreased the content of bound extracellular polymeric substances (B-EPS) and the ratio of protein to carbohydrate (PN/PS) by 17% and 48%, respectively and increased the relative hydrophobicity (RH) of the granules by 28%. The results of batch tests indicated that C8-HSL significantly reduced the content of loosely-bound EPS (LB-EPS) in the B-EPS, which was responsible for variations in granule settleability and stability. Thus, the settleability of the granules was improved significantly due to addition of C8-HSL, contributing to operational stability and the high TN removal efficiency of the reactor. On day 150, when the nitrogen loading rates of all reactors were 13.4 kg TN m−3 d−1, the nitrogen removal rate and nitrogen removal efficiency of the reactor with C8-HSL (R3) were up to 11.2 kg TN m−3 d−1 and 88%, respectively. N-hexanoyl-DL-homoserine lactone (C6-HSL) improved activity of the granules, while N-dodecanoyl-DL-homoserine lactone (C12-HSL) had no effect on the characteristics of the granules. The long-term effects of C8-HSL on the settleability of granules may be attributed to sustainable release of endogenous signals induced by exogenous signal.
•Additional C8-HSL improved ANAMMOX granules'settleability in high-loaded reactors.•Additional C6-HSL increased the activity of the ANAMMOX granules.•Additional C8-HSL or C6-HSL had long-term effects on the characteristics of granules.•Exogenous AHLs could induce the sustainable release of endogenous AHLs.•Opened a new window to control the flotation of the ANAMMOX granules.
Spatiotemporally regulated callose deposition is an essential, genetically programmed phenomenon that promotes pollen development and functionality. Severe male infertility is associated with ...deficient callose biosynthesis, highlighting the significance of intact callose deposition in male gametogenesis. The molecular mechanism that regulates the crucial role of callose in production of functional male gametophytes remains completely unexplored. Here, we provide evidence that the gradual upregulation of a previously uncharacterized cotton (
) pollen-specific SKS-like protein (PSP231), specifically at the post pollen-mitosis stage, activates callose biosynthesis to promote pollen maturation. Aberrant
expression levels caused by either silencing or overexpression resulted in late pollen developmental abnormalities and male infertility phenotypes in a dose-dependent manner, highlighting the importance of fine-tuned
expression. Mechanistic analyses revealed that PSP231 plays a central role in triggering and fine-tuning the callose synthesis and deposition required for pollen development. Specifically, PSP231 protein sequesters the cellular pool of RNA-binding protein GhRBPL1 to destabilize
mRNAs, turning off GhWRKY15-mediated transcriptional repression of
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and thus activating callose biosynthesis in pollen. This study showed that PSP231 is a key molecular switch that activates the molecular circuit controlling callose deposition toward pollen maturation and functionality and thereby safeguards agricultural crops against male infertility.
•Two types of innovative hybrid BPCS walls are proposed.•Pseudo-static tests of six BPCS wall and one MCS wall are conducted.•The failure mode and hysteretic property of BPCS walls are ...investigated.•Effects of bracing and SSR on seismic behavior of BPCS walls are evaluated.
This paper experimentally and numerically investigates the seismic behavior of two innovative types of hybrid precast concrete shear walls with diagonal-shaped or cross-shaped concealed bracings. Six 0.75-scaled braced precast concrete shear (BPCS) wall specimens and one monolithic cast-in-situ shear (MCS) wall were fabricated and employed to conduct the displacement-controlled pseudo-static tests. The length and thickness of the specimens were identical, whereas the heights of BPCS wall specimens were different owing to the different shear span ratios (SSRs) of 1.0, 1.5 and 2.0. Using the MCS wall specimen as a reference, the effects of bracing type and SSR on the seismic behavior of BPCS walls were studied in terms of failure mode, hysteretic behavior and energy dissipation capacity. Finite element (FE) analyses of the wall specimens were further performed using the multi-layer shell element model on the Opensees platform. The numerically calculated hysteresis loops of the wall specimens show good agreement with the experimental data, which proves that the employed FE model is adequately accurate in the seismic behavior assessment of BPCS walls. The experimental and numerical results indicate that the developed BPCS walls not only possess similar bearing capacity but also outperform the MCS wall in saving concrete usage and enhancing energy dissipation capacity. The diagonal and cross BPCS walls exhibit diametrically opposite characteristics as SSR increases. The diagonal BPCS wall with low SSR of 1.0 performs better in drift capacity, while the cross BPCS walls are more suitable for earthquake resistance at higher SSRs of 1.5 and 2.0.
Tai Chi has been shown to improve motor symptoms in Parkinson's disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects ...of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms.
Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi (n = 32), brisk walking (n = 31) and no-exercise (n = 32) groups. At baseline, 6 months and 12 months during one-year intervention, all participants underwent motor symptom evaluation by Berg balance scale (BBS), Unified PD rating-scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis, functional magnetic resonance imaging (fMRI), plasma cytokine and metabolomics analysis, and blood Huntingtin interaction protein 2 (HIP2) mRNA level analysis. Longitudinal self-changes were calculated using repeated measures ANOVA. GEE (generalized estimating equations) was used to assess factors associated with the longitudinal data of rating scales. Switch rates were used for fMRI analysis. False discovery rate correction was used for multiple correction.
Participants in the Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi was advantageous over brisk walking in improving BBS and step width. The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β. The improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, and increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training.
Long-term Tai Chi training improves motor function, especially gait and balance, in PD. The underlying mechanisms may include enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitter metabolism, and decreased vulnerability to dopaminergic degeneration. Trial registration This study has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR2000036036; Registration date: August 22, 2020).
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