The Chloride Channel (CLC) gene family is reported to be involved in vacuolar nitrate (NO3-) transport. Nitrate distribution to the cytoplasm is beneficial for enhancing NO3- assimilation and plays ...an important role in the regulation of nitrogen (N) use efficiency (NUE). In this study, genomic information, high-throughput transcriptional profiles, and gene co-expression analysis were integrated to identify the CLCs (BnaCLCs) in Brassica napus. The decreased NO3- concentration in the clca-2 mutant up-regulated the activities of nitrate reductase and glutamine synthetase, contributing to increase N assimilation and higher NUE in Arabidopsis thaliana. The genome-wide identification of 22BnaCLC genes experienced strong purifying selection. Segmental duplication was the major driving force in the expansion of the BnaCLC gene family. The most abundant cis-acting regulatory elements in the gene promoters, including DNA-binding One Zinc Finger, W-box, MYB, and GATA-box, might be involved in the transcriptional regulation of BnaCLCs expression. High-throughput transcriptional profiles and quantitative real-time PCR results showed that BnaCLCs responded differentially to distinct NO3- regimes. Transcriptomics-assisted gene co-expression network analysis identified BnaA7.CLCa-3 as the core member of the BnaCLC family, and this gene might play a central role in vacuolar NO3- transport in crops. The BnaCLC members also showed distinct expression patterns under phosphate depletion and cadmium toxicity. Taken together, our results provide comprehensive insights into the vacuolar BnaCLCs and establish baseline information for future studies on BnaCLCs-mediated vacuolar NO3- storage and its effect on NUE.
Hydrogen production by water-splitting is a very promising strategic energy technology and one of the most important means to obtain green hydrogen. It is of great practical significance to develop ...cheap and efficient electrocatalysts to replace Pt. Herein, we use the dye-sensitization strategy to load hyperdispersed Ru nanoparticles on the TiO2 surface, and then use cheap glucose for carbon coating to improve the conductivity of the material, so as to obtain an efficient HER catalyst C/Ru/TiO2. On the one hand, dye molecules can be firmly bonded to the surface of TiO2 through carboxyl groups, and on the other hand, their large steric effect can effectively inhibit the aggregation of molecules, so ruthenium nanoparticles formed after pyrolysis can be uniformly distributed on the surface of TiO2. Carbon coating also effectively solves the problem of poor conductivity of TiO2 as a support. C/Ru/TiO2 shows excellent catalytic performance for HER. In 0.5 M H2SO4, the overpotential is 69 mV at 10 mA cm−2 and the Tafel slope is only 70 mV dec−1. In 1 M KOH, the overpotential is only 51 mV at 10 mA cm−2 and the Tafel slope is only 68 mV dec−1. The dye-sensitization strategy makes it easy to realize the loading of hyperdisperse metal nanoparticles on the support surface.
Osteoarthritis, a highly prevalent degenerative joint disorder, is characterized by joint pain and disability. Available treatments fail to modify osteoarthritis progression and decrease joint pain ...effectively. Here, we show that intermittent parathyroid hormone (iPTH) attenuates osteoarthritis pain by inhibiting subchondral sensory innervation, subchondral bone deterioration, and articular cartilage degeneration in a destabilized medial meniscus (DMM) mouse model. We found that subchondral sensory innervation for osteoarthritis pain was significantly decreased in PTH-treated DMM mice compared with vehicle-treated DMM mice. In parallel, deterioration of subchondral bone microarchitecture in DMM mice was attenuated by iPTH treatment. Increased level of prostaglandin E2 in subchondral bone of DMM mice was reduced by iPTH treatment. Furthermore, uncoupled subchondral bone remodeling caused by increased transforming growth factor β signaling was regulated by PTH-induced endocytosis of the PTH type 1 receptor-transforming growth factor β type 2 receptor complex. Notably, iPTH improved subchondral bone microarchitecture and decreased level of prostaglandin E2 and sensory innervation of subchondral bone in DMM mice by acting specifically through PTH type 1 receptor in Nestin
mesenchymal stromal cells. Thus, iPTH could be a potential disease-modifying therapy for osteoarthritis.
Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that ...Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPβ, a rate-limiting enzyme in FAO. Although TPβ activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPβ association results in Nur77 self-sacrifice to protect TPβ from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPβ interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.
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•Nur77 facilitates metabolic adaptation of melanoma cells upon glucose deprivation•Glucose deprivation activates ERK2 to induce Nur77 mitochondrial translocation•Nur77 binds to TPβ and protects it from oxidation to facilitate FAO in mitochondria•The Nur77-TPβ axis promotes melanoma metastasis by supporting CTC survival
In this study, Li et al. demonstrate that the nuclear receptor Nur77 contributes to the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation-induced Nur77 mitochondrial translocation facilitates its interaction with TPβ, which protects TPβ from oxidation via Nur77 self-oxidation, boosting FAO to support cell survival under metabolic stress.
Alantolactone (ALA), a sesquiterpene lactone isolated from several medicinal plants such as Inula helenium, has been identified to have attractive anticancer activity. However, its role in the ...inhibition of angiogenesis during tumor development remains unclear. In this study, we found ALA can inhibit the proliferation, motility, migration, and tube formation of human umbilical vein endothelial cells. ALA also restrained angiogenesis in chick embryo chorioallantoic membrane and delayed the growth of human MDA‐MB‐231 breast cancer xenograft in mice through angiogenesis inhibition. Furthermore, ALA suppressed the phosphorylation of vascular endothelial growth factor receptor 2 and its downstream protein kinase including PLCγ1, FAK, Src, and Akt in endothelial cells. Taken together, the antiangiogenic activity of ALA and its molecular mechanism are identified for the first time, indicating that ALA may be a potential drug candidate or lead compound for antiangiogenic cancer therapy.
Nitrogen (N) is a macronutrient that is essential for optimal plant growth and seed yield. Allotetraploid rapeseed (A
A
C
C
, 2n = 4x = 38) has a higher requirement for N fertilizers whereas ...exhibiting a lower N use efficiency (NUE) than cereal crops. N limitation adaptation (NLA) is pivotal for enhancing crop NUE and reducing N fertilizer use in yield production. Therefore, revealing the genetic and molecular mechanisms underlying NLA is urgent for the genetic improvement of NUE in rapeseed and other crop species with complex genomes.
In this study, we integrated physiologic, genomic and transcriptomic analyses to comprehensively characterize the adaptive strategies of oilseed rape to N limitation stresses. Under N limitations, we detected accumulated anthocyanin, reduced nitrate (NO
) and total N concentrations, and enhanced glutamine synthetase activity in the N-starved rapeseed plants. High-throughput transcriptomics revealed that the pathways associated with N metabolism and carbon fixation were highly over-represented. The expression of the genes that were involved in efficient N uptake, translocation, remobilization and assimilation was significantly altered. Genome-wide identification and molecular characterization of the microR827-NLA1-NRT1.7 regulatory circuit indicated the crucial role of the ubiquitin-mediated post-translational pathway in the regulation of rapeseed NLA. Transcriptional analysis of the module genes revealed their significant functional divergence in response to N limitations between allotetraploid rapeseed and the model Arabidopsis. Association analysis in a rapeseed panel comprising 102 genotypes revealed that BnaC5.NLA1 expression was closely correlated with the rapeseed low-N tolerance.
We identified the physiologic and genome-wide transcriptional responses of oilseed rape to N limitation stresses, and characterized the global members of the BnamiR827-BnaNLA1s-BnaNRT1.7s regulatory circuit. The transcriptomics-assisted gene co-expression network analysis accelerates the rapid identification of central members within large gene families of plant species with complex genomes. These findings would enhance our comprehensive understanding of the physiologic responses, genomic adaptation and transcriptomic alterations of oilseed rape to N limitations and provide central gene resources for the genetic improvement of crop NLA and NUE.
Microorganisms may persist in the root canal system after root canal therapy (RCT). The purpose of this study was to explore the metronidazole (MTR)- and chlorhexidine (CHX)-loaded hydrogels as the ...potential application in intracanal medicaments for root canal disinfection. Ultraviolet cross-linked hydrogels (gGels) were synthesized by GelMA solution and photoinitiator, which were loaded with MTR (MTR@gGels) and CHX (CHX@gGels). gGels, MTR@gGels and CHX@gGels were characterized by scanning electron microscopy. The antimicrobial activity against E. faecalis, S. mutans and P. intermedia was assessed. Meanwhile, the biocompatibility of human dental pulp stem cells (hDPSCs) was evaluated. DCT, CCK-8, CFU and live/dead-stained biofilm results showed that the viability of E. faecalis, S. mutans and P. intermedia was significantly reduced in MTR@gGels and CHX@gGels in vitro. CCK-8 results showed considerable biocompatibility with hDPSCs. The filling and clearance of gGels in root canals were demonstrated in vivo. Therefore, MTR- and CHX-loaded hydrogels may be a potential application in intracanal medicaments for root canal disinfection.
Improving crop nitrogen (N) limitation adaptation (NLA) is a core approach to enhance N use efficiency (NUE) and reduce N fertilizer application. Rapeseed has a high demand for N nutrients for ...optimal plant growth and seed production, but it exhibits low NUE. Epigenetic modification, such as DNA methylation and modification from small RNAs, is key to plant adaptive responses to various stresses. However, epigenetic regulatory mechanisms underlying NLA and NUE remain elusive in allotetraploid
. In this study, we identified overaccumulated carbohydrate, and improved primary and lateral roots in rapeseed plants under N limitation, which resulted in decreased plant nitrate concentrations, enhanced root-to-shoot N translocation, and increased NUE. Transcriptomics and RT-qPCR assays revealed that N limitation induced the expression of
,
,
,
, and
, and repressed the transcriptional levels of
,
, and
. High-resolution whole genome bisulfite sequencing characterized 5094 differentially methylated genes involving ubiquitin-mediated proteolysis, N recycling, and phytohormone metabolism under N limitation. Hypermethylation/hypomethylation in promoter regions or gene bodies of some key N-metabolism genes might be involved in their transcriptional regulation by N limitation. Genome-wide miRNA sequencing identified 224 N limitation-responsive differentially expressed miRNAs regulating leaf development, amino acid metabolism, and plant hormone signal transduction. Furthermore, degradome sequencing and RT-qPCR assays revealed the miR827-NLA pathway regulating limited N-induced leaf senescence as well as the miR171-
and miR160-
pathways regulating root growth under N deficiency. Our study provides a comprehensive insight into the epigenetic regulatory mechanisms underlying rapeseed NLA, and it will be helpful for genetic engineering of NUE in crop species through epigenetic modification of some N metabolism-associated genes.
Background and aims The two-component high-affinity nitrate (NO3−) transport system (THATS) proteins (NRT2/NAR2) play key roles in the efficient nitrogen (N) uptake and transport under N limitations. ...We aimed at uncovering the core THATS gene(s) regulating N use efficiency (NUE) in allotetraploid rapeseed (Brassica napus L.). Methods Genomic information, high-throughput transcriptome sequencing and gene co-expression network were integrated to identify and characterize the core THATS genes. Results We identified 17 BnaNRT2 and eight BnaNAR2.1 homologs spanning across the rapeseed genome. Copy number and gene presence/absence variations of BnaNRT2s/BnaNAR2.1 s, undergoing strong purifying selection, occurred. The over-representation of Dof, MYB and WRKY cis-regulatory elements and the enrichment of CpG islands, and protein phosphorylation sites indicated the importance of transcriptional and epigenetic regulation in the BnaNRT2 activities, respectively. qRT-PCR assays and high-throughput RNA-seq revealed that both BnaNRT2s and BnaNAR2.1 s were expressed preferentially in the roots; and they showed significantly differential expression under different N forms or different levels of NO3− supply. A gene co-expression network identified BnaC8.NRT2.1a and BnaC2.NAR2.1 as the core THATS genes. Conclusions The core THATS members can serve as elite gene resources for crop NUE improvement. The transcriptomics-assisted gene co-expression network analysis provides novel insights regarding the rapid identification of central members within large gene families of plant species with complex genomes.
Herein, we prepared two new zinc porphyrin dyes ( JA4 and JA5 ) containing different anchoring groups and applied them in dye-sensitized solar cells. The hydrazide unit was used as an anchoring group ...for a DSSC, and the device based on the JA5 containing hydrazide anchor also shows a high PCE of 5.49% with a J sc of 11.57 mA cm −2 and a V oc of 737 mV. COOH is the most common anchor, but it is prone to dissociate from the TiO 2 surface, especially under alkaline conditions. Interestingly, the hydrazide anchor shows better water-stability under various aqueous conditions compared with the COOH anchor, including acidic, neutral and alkaline conditions. In addition, a hydrazide unit is very easy to synthesise, thus, hydrazide can be a promising anchoring group for DSSCs.
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