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Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were established by unilateral labyrinthectomy (UL) and infusion with siBDNF or 7, 8-Dihydroxyflavone (7,8-DHF, a TrkB receptor agonist). The behavioral scores of rats with vestibular deficits were determined and the rotarod test was performed after UL. BDNF and TrkB levels after UL were determined by western blot and quantitative reverse transcription PCR (qRT-PCR). 5-bromo-2ʹ-deoxyuridine (BrdU)-positive cells (newly generated cells) and GAD67-positive cells (GABAergic neurons) were identified by immunohistochemistry. Glial fibrillary acidic protein (GFAP) (astrocyte marker)-positive cells were identified and GABA type A receptor (GABAAR) expression was detected by immunofluorescence. We found that after UL, BDNF and TrkB levels were up-regulated with a maximum value at 4 h, and then progressively down-regulated during 4 h ~ 7 d. Blocking BDNF/TrkB signaling inhibited the recovery from vestibular deficits, decreased the numbers of newly generated cells and astrocytes in medial vestibular nucleus (MVN), inferior vestibular nerve (IVN), superior vestibular nerve (SVN) and lateral vestibular nucleus (LVN), and disrupted the balances of GABAergic neurons and GABAAR expressions in the left (lesioned) side and right (intact) side of MVN, whereas activation of BDNF/TrkB signaling caused opposite results. The current study indicated that BDNF/TrkB signaling avails vestibular compensation, depending on the number of newly generated cells and astrocytes, the rebalance of GABAergic neurons, and GABAAR expression in bilateral MVN.

Rhizosphere microorganisms interact with plant roots by producing chemical signals that regulate root development. However, the distinct bioactive compounds and signal transduction pathways remain to be identified. Here, we showed that sesquiterpenes are the main volatile compounds produced by plant-beneficial Trichoderma guizhouense NJAU4742. Inhibition of sesquiterpene biosynthesis eliminated the promoting effect of this strain on root growth, indicating its involvement in plant-fungus cross-kingdom signalling. Sesquiterpene component analysis identified cedrene, a highly abundant sesquiterpene in strain NJAU4742, to stimulate plant growth and root development. Genetic analysis and auxin transport inhibition showed that the TIR1 and AFB2 auxin receptors, IAA14 auxin-responsive protein, and ARF7 and ARF19 transcription factors affected the response of lateral roots to cedrene. Moreover, the AUX1 auxin influx carrier and PIN2 efflux carrier were also found to be indispensable for cedrene-induced lateral root formation. Confocal imaging showed that cedrene affected the expression of pPIN2:PIN2:GFP and pPIN3:PIN3:GFP, which might be related to the effect of cedrene on root morphology. These results suggested that a novel sesquiterpene molecule from plant-beneficial T. guizhouense regulates plant root development through the transport and signalling of auxin.

We studied the effects of heterozygous human INS gene mutations on insulin secretion, endoplasmic reticulum (ER) stress and other mechanisms in both MIN6 and human induced pluripotent stem cells (hiPSC)-derived beta-like cells, as well as the effects of prolonged overexpression of mutant human INS in MIN6 cells. We modelled the structure of mutant C109Y and G32V proinsulin computationally to examine the in silico effects. We then overexpressed either wild-type (WT), mutant (C109Y or G32V), or both WT and mutant human preproinsulin in MIN6 cells, both transiently and stably over several weeks. We measured the levels of human and rodent insulin secreted, and examined the transcript and protein levels of several ER stress and apoptotic markers. We also reprogrammed human donor fibroblasts heterozygous for the C109Y mutation into hiPSCs and differentiated these into pancreatic beta-like cells, which were subjected to single-cell RNA-sequencing and transcript and protein analyses for ER stress and apoptotic markers. The computational modelling studies, and short-term and long-term expression studies in beta cells, revealed the presence of ER stress, organelle changes and insulin processing defects, resulting in a decreased amount of insulin secreted but not the ability to secrete insulin. By 9 weeks of expression of mutant human INS, dominant-negative effects of mutant INS were evident and beta cell insulin secretory capacity declined. INS+/C109Y patient-derived beta-like cells and single-cell RNA-sequencing analyses then revealed compensatory upregulation in genes involved in insulin secretion, processing and inflammatory response. The results provide deeper insights into the mechanisms of beta cell failure during INS mutation-mediated diabetes disease progression. Decreasing spliced X-box binding protein 1 (sXBP1) or inflammatory response could be avenues to restore the function of the remaining WT INS allele.

Microbial fabrication is eco-friendly for nobel-metal catalysts typically used in proton exchange membrane fuel cell (PEMFC). In our study, nano-Pd electrocatalysts were successfully prepared by using three Shewanellas as precursors through hydrogen reduction (200 °C) and carbonization (800 °C). The analysis revealed that the catalysts showed outstanding ORR electrocatalytic performance via a predominant four-electron oxygen reduction pathway in alkaline medium. The best performance was obtained for Pd/HNC-32, which showed a mass activity at 0.526 A mg−1, 3.78 times higher than that of commercial Pd/C. Shewanella putrefaciens CN-32 was a more effective Pd-adsorbent. The enhanced performance can be ascribed to the small Pd-particle size and uniform dispersion on microbial support, which results from stronger hydrophilicity of Shewanella putrefaciens CN-32. The content of nitrogen is another key to the performance of Pd/HNC-32. This study developed a promising strategy for screening microbial strains for electrocatalyst fabrication.

In this paper, we achieved excellent variation control, endurance enhancement, and leakage reduction in zirconium (Zr)-doped hafnium oxide (Hf1–xZrxO2) based ferroelectric films by the germination ...

Increased use of nitrogen fertilizers has deleterious impact on the environment. Increase in yield potential at low nitrogen supply is regarded as a cereal breeding goal for future agricultural sustainability. Although natural variations of nitrogen transporters have been investigated, key genes associated with assimilation remain largely unexplored for nitrogen use efficiency (NUE) enhancement. Here, we identified a NIN‐like protein NLP4 associated with NUE through a GWAS in rice. We found that OsNLP4 transactivated OsNiR encoding nitrite reductase that was critical in nitrogen assimilation in rice. We further constructed quadrupling NREs (Nitrate‐responsive cis‐elements) in the promoter of OsNiR (p4xNRE:OsNiR) and enhanced nitrogen assimilation significantly. We demonstrated that OsNLP4‐OsNiR increased tiller number and yield through enhancing nitrogen assimilation and NUE. Our discovery highlights the genetic modulation of OsNLP4‐OsNiR signalling cascade as a strategy for high NUE and yield breeding in rice.

Over-application of nitrogen fertilizer in fields has had a negative impact on both environment and human health. Domesticated rice varieties with high nitrogen use efficiency (NUE) reduce fertilizer for sustainable agriculture. Here, we perform genome-wide association analysis of a diverse rice population displaying extreme nitrogen-related phenotypes over three successive years in the field, and identify an elite haplotype of nitrate transporter OsNPF6.1HapB that enhances nitrate uptake and confers high NUE by increasing yield under low nitrogen supply. OsNPF6.1HapB differs in both the protein and promoter element with natural variations, which are differentially trans-activated by OsNAC42, a NUE-related transcription factor. The rare natural allele OsNPF6.1HapB, derived from variation in wild rice and selected for enhancing both NUE and yield, has been lost in 90.3% of rice varieties due to the increased application of fertilizer. Our discovery highlights this NAC42-NPF6.1 signaling cascade as a strategy for high NUE and yield breeding in rice., Improving crop nitrogen use efficiency can facilitate sustainable production, however, the genetic mechanisms have not been fully revealed. Here, the authors discover the NAC42-NPF6.1 signaling cascade mainly derives from indica and wild rice and demonstrate the potential of using the allele for cultivar improvement.

The plant hormones brassinosteroids (BRs) and auxin interact to regulate root meristem size. A new study reveals dual and opposing roles for BRs in auxin biosynthesis and signaling output in the Arabidopsis root epidermis, demonstrating that epidermis-derived BR signaling is required for root meristem maintenance through its effect on auxin signaling.

Caffeine is one of the most widely used psychostimulants in the world and possesses central excitative, anti-depressive, and neuroprotective properties. However, excessive ingestion or abuse of caffeine can lead to intoxication. Many toxic effects are attributed to oxidative damage, and nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical intracellular regulator of the oxidative stress response. Here, we investigated the neurotoxicity of caffeine in rat pheochromocytoma PC12 cells and zebrafish larvae. It was found that caffeine inhibited the viability of PC12 cells in a dose- and time-dependent manner. Furthermore, it induced PC12 cell apoptosis and elevated reactive oxygen species (ROS) production. Quantitative polymerase chain reaction (qPCR) and western blotting revealed that caffeine also inhibited the expression levels of Nrf2 mRNA and protein and its target genes (e.g., NADPH quinone oxidoreductase 1 [NQO1]). Furthermore, Nrf2 silencing attenuated the toxic effects of caffeine. In addition, zebrafish larvae were treated with different doses of caffeine. Behavioral experiments showed that a low dose of caffeine (0.05 to 0.3 mM) increased the average distance of movement and promoted excitation. Survivorship curves showed that caffeine (0.2 to 1.5 mM) caused lethality. Finally, qPCR revealed that a higher dose of caffeine inhibited mRNA levels in the Nrf2 pathway. Based on these results, this study identified for the first time that overuse of caffeine can induce neurotoxicity by inhibiting the Nrf2 pathway. These results will provide a new perspective for studies on caffeine toxicity.

In this article we proclaim excellent improvement in the defect densities in hafnium zirconium oxide based ferroelectric film obtained by extending the duration of post-metallization annealing up to 180s. The consequences of extending the annealing duration on the structure and surface morphology was gauged by XRD analysis, HR-TEM and AFM, which showed increase in the grain size, well defined crystallinity, lower defect densities and negligible impact on surface roughness. The electrical characterization revealed reduction in RC leakage along with a significant improvement in flicker noise and random telegraphic noise characteristics, which proves reduction of defect densities when the annealing time is increased.

Rhizosphere microorganisms interact with plant roots by producing chemical signals to regulate root development. However, the involved distinct bioactive compounds and the signal transduction pathways are remaining to be identified. Here, we show that sesquiterpenes (SQTs) are the main volatile compounds produced by plant beneficialTrichoderma guizhouenseNJAU 4742, inhibition of SQTs synthesis in this strain indicated their involvement in plant-fungus cross-kingdom signaling. SQTs component analysis further identified the cedrene, a high abundant SQT in strain NJAU 4742, could stimulate plant growth and root development. Genetic analysis and auxin transport inhibition showed that auxin receptor TIR1, AFB2, auxin-responsive protein IAA14, and transcription factor ARF7, ARF19 affect the response of lateral roots to cedrene. Moreover, auxin influx carrier AUX1, efflux carrier PIN2 were also indispensable for cedrene-induced lateral root formation. Confocal imaging showed that cedrene affected the expression ofpPIN2:PIN2:GFPandpPIN3:PIN3:GFP, which may be related to the effect of cedrene on root morphology. These results suggest that a novel SQT molecule from plant beneficialT. guizhouensecan regulate plant root development through auxin transport and signaling.One-sentence SummaryCedrene, a high- abundance sesquiterpenes produced by plant beneficialTrichoderma guizhouenseNJAU 4742, stimulatesArabidopsislateral root formation and primary root elongation by relying on auxin signaling pathway and auxin transporter PIN2 and AUX1.

About 10 million people in China are infected with hepatitis C virus (HCV), with the seroprevalence of anti-HCV in the general population estimated at 0.6%. Delaying effective treatment of chronic hepatitis C (CHC) is associated with liver disease progression, cirrhosis, hepatocellular carcinoma, and liver-related mortality. The extrahepatic manifestations of CHC further add to the disease burden of patients. Managing CHC-related advanced liver diseases and systemic manifestations are costly for both the healthcare system and society. Loss of work productivity due to reduced well-being and quality of life in CHC patients further compounds the economic burden of the disease. Traditionally, pegylated-interferon plus ribavirin (PR) was the standard of care. However, a substantial number of patients are ineligible for PR treatment, and only 40%-75% achieved sustained virologic response. Furthermore, PR is associated with impairment of patient-reported outcomes (PROs), high rates of adverse events, and poor adherence. With the advent of direct acting antivirals (DAAs), the treatment of CHC patients has been revolutionized. DAAs have broader eligible patient populations, higher efficacy, better PRO profiles, fewer adverse events, and better adherence rates, thereby making it possible to cure a large proportion of all CHC patients. This article aims to provide a comprehensive evaluation on the value of effective, curative hepatitis C treatment from the clinical, economic, societal, and patient experience perspectives, with a focus on recent data from China, supplemented with other Asian and international experiences where China data are not available.

Three new coordination polymers, [Zn(H2L2)(H2O)]n (1), [Cd(H2L2)(H2O)]n (2) and {[Pb(H2L2)]n (3) (H4L = 1,1′-(propane-1,3-diyl)bis(1H-imidazole-4,5-dicarboxylic acid)) have been successfully prepared under hydrothermal conditions. Complexes 1 and 2 are isomorphic and exhibit 2D fes network constructed from interconnected ring-like [M2(H2L)2] (M = Zn or Cd) MBBs. Complex 3 displays a 3D covalent framework with seh-3,5-P21/c net topology built by interconnected ring-like [Pb4(H2L)2] MBBs. Moreover, the thermal stability and fluorescent properties of these complexes were investigated in detail.

The anti‐inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA‐pretreated human chondrocytes showed lower levels of interleukin (IL)‐1β‐induced IL‐6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor‐α (TNF‐α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase‐9 (MMP‐9) and matrix metalloproteinase‐13 (MMP‐13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‐2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)‐5. Furthermore, activation of nuclear factor κB (NF‐κB), which was induced by IL‐1β, was also inhibited by SA through the pathway of nuclear factor‐erythroid 2‐related factor‐2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.

Remodeling of auxin distribution during the integration of plant growth responses with the environment requires the precise control of auxin influx and efflux transporters. The plasma membrane-localized PIN-FORMED (PIN) proteins facilitate auxin efflux from cells, and their activity is regulated by reversible phosphorylation. How PIN modulates plant cellular responses to external stresses and whether its activity is coordinated by phospholipids remain unclear. Here, we reveal that, in Arabidopsis (Arabidopsis thaliana), the phosphatidic acid (PA)-regulated PINOID (PID) kinase is a crucial modulator of PIN2 activity and auxin redistribution in response to salt stress. Under salt stress, loss of phospholipase D function impaired auxin redistribution and resulted in markedly reduced primary root growth; these effects were reversed by exogenous PA. The phospholipase D-derived PA interacted with PID and increased PID-dependent phosphorylation of PIN2, which activated auxin efflux and altered auxin accumulation, promoting root growth when exposed to salt stress. Ablation of the PA binding motif not only diminished PID accumulation at the plasma membrane but also abolished PA-promoted PID phosphorylation of PIN2 and its function in coping with salt stress; however, this ablation did not affect inflorescence and cotyledon development or PIN2-dependent gravitropic and halotropic responses. Our data indicate a role for PA in coupling extracellular salt signaling to PID-directed PIN2 phosphorylation and polar auxin transport, highlighting the importance of lipid-protein interactions in the spatiotemporal regulation of auxin signaling.

Lateral root branching along the primary root involves complex gene regulatory networks in model plant Arabidopsis. However, it is largely unclarified whether different plant species share a common mechanism to pattern the lateral root along the primary axis. In this study, we assessed the development pattern of lateral root among several dicot and monocot plants, including Arabidopsis, tomato, Medicago, Nicotiana, rice, and ryegrass by using an agar-gel culture system. Our results reveal a regular-spaced distribution pattern of lateral roots along the primary root axis of both dicot and monocot plants. Meanwhile, the root patterning is tightly controlled by root bending and the plant hormone auxin. However, nitrogen and phosphate starvations trigger distinguished root growth patterns among different plant species. Our studies strongly suggest a partially shared signaling pathway underlying root patterning of various plant species, and also provide a foundation for further identification of genes associated with root development.

Lateral root formation is coordinated by both endogenous and external factors. As biotic factors, plant growth-promoting rhizobacteria can affect lateral root formation, while the regulation mechanism is unclear. In this study, by applying various marker lines, we found that volatile compounds (VCs) from Bacillus amyloliquefaciens SQR9 induced higher frequency of DR5 oscillation and prebranch site formation, accelerated the development and emergence of the lateral root primordia and thus promoted lateral root development in Arabidopsis. We demonstrated a critical role of auxin on B. amyloliquefaciens VCs-induced lateral root formation via respective mutants and pharmacological experiments. Our results showed that auxin biosynthesis, polar transport and signalling pathway are involved in B. amyloliquefaciens VCs-induced lateral roots formation. We further showed that acetoin, a major component of B. amyloliquefaciens VCs, is less active in promoting root development compared to VC blends from B. amyloliquefaciens, indicating the presence of yet uncharacterized/unknown VCs might contribute to B. amyloliquefaciens effect on lateral root formation. In summary, our study revealed an auxin-dependent mechanism of B. amyloliquefaciens VCs in regulating lateral root branching in a non-contact manner, and further efforts will explore useful VCs to promote plant root development.

To mitigate the environmental impact induced by CO2 emissions and nonrenewable resource consumption, which are typically associated with Portland cement production, ground granulated blast furnace slags (GGBSs) are usually added to the cement. In this study, the stabilisation effect of alkali-activated GGBS on saline soil and the hydration products of alkali-activated GGBS were investigated by unconfined compressive strength tests and scanning electron microscopy, respectively. The results show that Ca(OH)2 and NaOH as alkaline activators for GGBS significantly improve the unconfined compressive strength of saline soils. This strength is also enhanced by Na2SO4; however, the increase is considerably less than that provided by Ca(OH)2 and NaOH. In contrast, Na2CO3 is not a suitable alkaline activator for GGBS and has no significant effect on the unconfined compressive strength of saline soils. The study results further show that the morphology of hydration products varies because of the different alkaline activators involved in the hydration reaction with GGBS in saline soils.

The spacing of lateral roots (LRs) along the main root in plants is driven by an oscillatory signal, often referred to as the "root clock" that represents a pre-patterning mechanism that can be influenced by environmental signals. Light is an important environmental factor that has been previously reported to be capable of modulating the root clock, although the effect of light signaling on the LR pre-patterning has not yet been fully investigated. In this study, we reveal that light can activate the transcription of a photomorphogenic gene HY1 to maintain high frequency and amplitude of the oscillation signal, leading to the repetitive formation of pre-branch sites. By grafting and tissue-specific complementation experiments, we demonstrated that HY1 generated in the shoot or locally in xylem pole pericycle cells was sufficient to regulate LR branching. We further found that HY1 can induce the expression of HY5 and its homolog HYH, and act as a signalosome to modulate the intracellular localization and expression of auxin transporters, in turn promoting auxin accumulation in the oscillation zone to stimulate LR branching. These fundamental mechanistic insights improve our understanding of the molecular basis of light-controlled LR formation and provide a genetic interconnection between shoot- and root-derived signals in regulating periodic LR branching.

Objective Transdifferentiation exists between stromal cells or between stromal cells and cancer cells. Evodiamine and berberine are predominant pharmacological components of Zuojin pill, a prescription of Traditional Chinese Medicine, playing crucial functions in remolding of tumor microenvironment. This study aimed to explore the effect of combination of evodiamine with berberine (cBerEvo) on the phenotypic transition of colon epithelial cells induced by tumor-associated fibroblasts, as well as the involved mechanisms.Methods Human normal colon epithelial cell line HCoEpiC cells were treated with the prepared conditioned medium of CCD-18Co, a human colon myofibroblast line, to induce epithelial-mesenchymal transition. Phase contrast microscope was used to observe the morphological changes. Epithelial-mesenchymal transition markers including E-cadherin, vimentin and alpha-smooth muscle actin (α-SMA) were observed with immunofluorescence microscopy. Migration was assessed by wound healing assay. Western blotting was used to detect the expressions of E-cadherin, vimentin, α-SMA, Snail, ZEB1 and Smads. Results In contrast to the control, the tumor-associated fibroblasts-like CCD-18Co cells induced down-regulation of E-cadherin and up-regulation of vimentin, α-SMA, Snail and ZEB1 (P

Cadmium (Cd) strongly inhibits root growth, especially the formation of lateral roots (LRs). The mechanism of Cd inhibition on LR formation in rice (Oryza sativa) remains unclear. In this study, we found that LR emergence in rice was inhibited significantly by 1 �M Cd and almost completely arrested by 5 �M Cd. Cd suppressed both the formation and subsequent development of the lateral root primordium (LRP). By using transgenic rice expressing the auxin response reporters DR5::GUS and DR5rev::VENUS, we found that Cd markedly reduced the auxin levels in the stele and LRP. Cd rapidly downregulated the expression of the auxin efflux transporter genes OsPIN1b, OsPIN1c and OsPIN9 in the stele and LRP. The emergence of LRs in a rice cultivar with a null allele of OsHMA3 (Heavy Metal ATPase 3) was more sensitive to Cd than cultivars with functional alleles. Overexpression of functional OsHMA3 in rice greatly alleviated the inhibitory effect of Cd, but the protective effect of OsHMA3 was abolished by the auxin polar transport inhibitor 1-N-naphthylphthalamic acid. The results suggest that Cd inhibits LR development in rice by disrupting OsPIN-mediated auxin distribution to LRP and OsHMA3 protects against Cd toxicity by sequestering Cd into the vacuoles.

Photorespiratory hydrogen peroxide (H2 O2 ) plays key roles in pathogenesis responses by triggering the salicylic acid (SA) pathway in Arabidopsis. However, factors linking intracellular H2 O2 to activation of the SA pathway remain elusive. In this work, the catalase-deficient Arabidopsis mutant, cat2, was exploited to elucidate the impact of S-nitrosoglutathione reductase 1 (GSNOR1) on H2 O2 -dependent signalling pathways. Introducing the gsnor1-3 mutation into the cat2 background increased S-nitrosothiol levels and abolished cat2-triggered cell death, SA accumulation, and associated gene expression but had little additional effect on the major components of the ascorbate-glutathione system or glycolate oxidase activities. Differential transcriptome profiles between gsnor1-3 and cat2 gsnor1-3 together with damped ROS-triggered gene expression in cat2 gsnor1-3 further indicated that GSNOR1 acts to mediate the SA pathway downstream of H2 O2 . Up-regulation of GSNOR activity was compromised in cat2 cad2 and cat2 pad2 mutants in which glutathione accumulation was genetically prevented. Experiments with purified recombinant GSNOR revealed that the enzyme is posttranslationally regulated by direct denitrosation in a glutathione-dependent manner. Together, our findings identify GSNOR1-controlled nitrosation as a key factor in activation of the SA pathway by H2 O2 and reveal that glutathione is required to maintain this biological function.

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1β (IL-1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1β-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.

High levels of ammonium nutrition reduce plant growth and different plant species have developed distinct strategies to maximize ammonium acquisition while alleviating ammonium toxicity through modulating root growth. To date, the mechanisms underlying plant tolerance or sensitivity towards ammonium remain unclear. Rice (Oryza sativa) uses ammonium as its main N source. Here we show that ammonium supply restricts rice root elongation and induces a helical growth pattern, which is attributed to root acidification resulting from ammonium uptake. Ammonium-induced low pH triggers the asymmetric distribution of auxin in rice root tips through changes in auxin signaling, thereby inducing a helical growth response. Blocking auxin signaling completely inhibited this root response. In contrast, this root response is not activated in ammonium-treated Arabidopsis. Acidification of Arabidopsis roots leads to the protonation of indole-3-acetic acid and dampening of the intracellular auxin signaling levels that are required for maintaining root growth. Our study suggests a different mode of action by ammonium on the root pattern and auxin response machinery in rice versus Arabidopsis, and the rice-specific helical root response towards ammonium is an expression of the ability of rice to moderate auxin signaling and root growth to utilize ammonium while confronting acidic stress.

Plant root architecture dynamically adapts to various environmental conditions, such as salt‐containing soil. The phytohormone abscisic acid (ABA) is involved among others also in these developmental adaptations, but the underlying molecular mechanism remains elusive. Here, a novel branch of the ABA signaling pathway in Arabidopsis involving PYR/PYL/RCAR (abbreviated as PYLs) receptor‐protein phosphatase 2A (PP2A) complex that acts in parallel to the canonical PYLs‐protein phosphatase 2C (PP2C) mechanism is identified. The PYLs‐PP2A signaling modulates root gravitropism and lateral root formation through regulating phytohormone auxin transport. In optimal conditions, PYLs ABA receptor interacts with the catalytic subunits of PP2A, increasing their phosphatase activity and thus counteracting PINOID (PID) kinase‐mediated phosphorylation of PIN‐FORMED (PIN) auxin transporters. By contrast, in salt and osmotic stress conditions, ABA binds to PYLs, inhibiting the PP2A activity, which leads to increased PIN phosphorylation and consequently modulated directional auxin transport leading to adapted root architecture. This work reveals an adaptive mechanism that may flexibly adjust plant root growth to withstand saline and osmotic stresses. It occurs via the cross‐talk between the stress hormone ABA and the versatile developmental regulator auxin., A novel branch of the ABA signaling pathway in Arabidopsis involving PYLs ABA receptor‐PP2A protein phosphatase complex, which modulates root gravitropism and lateral root formation through regulating phytohormone auxin transport, is identified. This work reveals an adaptive mechanism that may flexibly adjust plant root architecture to avoid the damage resulting from environmental stresses.

The proteome and phosphoproteome of CEP5 overexpressing Arabidopsis seedlings have been determined. This revealed that CEP5 impacts abiotic stress-related processes. Subsequent genetic, physiological, biochemical, and pharmacological results demonstrated that CEP5-mediated signaling is relevant for osmotic and drought stress tolerance in Arabidopsis. Furthermore, CEP5 specifically counteracts auxin effects by stabilizing AUX/IAA transcriptional repressors., Graphical Abstract Highlights • Quantitative Arabidopsis (phospho)proteomes of C-TERMINALLY ENCODED PEPTIDE 5 (CEP5). • CEP5 impacts abiotic stress-related processes and counteracts auxin effects. • CEP5 signaling stabilizes AUX/IAA transcriptional repressors. • Novel peptide-dependent control mechanism that tunes auxin signaling., Peptides derived from non-functional precursors play important roles in various developmental processes, but also in (a)biotic stress signaling. Our (phospho)proteome-wide analyses of C-TERMINALLY ENCODED PEPTIDE 5 (CEP5)-mediated changes revealed an impact on abiotic stress-related processes. Drought has a dramatic impact on plant growth, development and reproduction, and the plant hormone auxin plays a role in drought responses. Our genetic, physiological, biochemical, and pharmacological results demonstrated that CEP5-mediated signaling is relevant for osmotic and drought stress tolerance in Arabidopsis, and that CEP5 specifically counteracts auxin effects. Specifically, we found that CEP5 signaling stabilizes AUX/IAA transcriptional repressors, suggesting the existence of a novel peptide-dependent control mechanism that tunes auxin signaling. These observations align with the recently described role of AUX/IAAs in stress tolerance and provide a novel role for CEP5 in osmotic and drought stress tolerance.

Background/Aims: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. Results: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/β and suppressed the IL-1β-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1β-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. Conclusion: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1β-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.

Background Tea plant (Camellia sinensis) is one of the most popular non-alcoholic beverages worldwide. In tea, lateral roots (LRs) are the main organ responsible for the absorption of moisture and mineral nutrients from the soil. Lateral roots formation and development are regulated by the nitrogen and auxin signaling pathways. In order to understand the role of auxin and nitrogen signaling in LRs formation and development, transcriptome analysis was employed to investigate the differentially expressed genes involved in lateral roots of tea plants treated with indole-3-butyric acid (IBA), N-1-naphthylphthalamic acid (NPA), low and high concentrations of nitrogen. Results A total of 296 common differentially expressed genes were identified and annotated to four signaling pathways, including nitrogen metabolism, plant hormone signal transduction, glutathione metabolism and transcription factors. RNA-sequencing results revealed that majority of differentially expressed genes play important roles in nitrogen metabolism and hormonal signal transduction. Low nitrogen condition induced the biosynthesis of auxin and accumulation of transcripts, thereby, regulating lateral roots formation. Furthermore, metabolism of cytokinin and ethylene biosynthesis were also involved in lateral roots development. Transcription factors like MYB genes also contributed to lateral roots formation of tea plants through secondary cell wall biosynthesis. Reversed phase ultra performance liquid chromatography (RP-UPLC) results showed that the auxin concentration increased with the decreased nitrogen level in lateral roots. Thus, tea plant lateral roots formation could be induced by low nitrogen concentration via auxin biosynthesis and accumulation. Conclusion This study provided insights into the mechanisms associated with nitrogen and auxin signaling pathways in LRs formation and provides information on the efficient utilization of nitrogen in tea plant at the genetic level.

ObjectiveInconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination.DesignA systematic review and network meta-analysis.Data sourcesRandomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017.OutcomesTotal fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted.ResultsA total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures.ConclusionsThe use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully.PROSPERO registration numberCRD42017079624.

The hydrogen evolution reaction (HER) is a critical step in water splitting and demands efficient and low-cost catalysts for real applications. Pt catalyzes HER efficiently, however, its scarcity and high cost inspire researchers to explore metallic catalysts with core-shell nanostructures. Precise tailoring of Pt catalysts at atomic monolayer level would shed insights on the relationship between electronic structure and electrocatalytic properties. Herein, we report the preparation of Au-Pt core-shell nanoparticles deposited on graphene sheets with tunable Pt monolayer coverage by controlling Cu underpotential deposition (UPD)-Galvanic replacement cycles. The electrochemical results suggest that Au-Pt with monolayer Pt shows superior electrocatalytic activity toward HER. Increasing the thickness of Pt shell results in the decrease of the electrocatalytic activity, which might be attributed to the decreased electronic interactions of Au core with outmost surface Pt atoms as confirmed by X-ray photoelectron spectroscopic characterization. The present research would offer a design criterion for metallic nanostructures in realizing catalysts with high performance.

Cabernet Gernischt (CG) is a famous Chinese wine grape cultivar, the red wine of which is known for its green trait, especially when produced from grapes cultivated in regions with monsoon climate. To modify CG wine aroma, three enzyme preparations (H. uvarum extracellular enzyme, AR2000, and pectinase) were introduced in different winemaking stages with Saccharomyces cerevisiae. Free and bound aroma compounds in young wines were detected using headspace solid-phase micro-extraction and gas chromatography-mass spectrometry, and aroma characteristics were quantified by trained panelists. Results showed that simultaneous inoculation of enzymes and yeasts improved wine aroma. Partial least-squares regression revealed that the green trait was due mainly to varietal compounds, especially C6 compounds, and could be partly weakened by fermentative compounds. Moreover, H. uvarum enzyme treatments enriched the acid fruit note of CG wine by enhancing the synergistic effect of varietal volatiles and certain fermentative compounds, such as esters and phenylethyls.

We constructed a series of novel chiral molecular face-rotating polyhedra (FRP) from two 10,15-dihydro-5H-diindolo[3,2-a:3',2'-c]carbazole (triazatruxene) derivatives and trans-1,2-cyclohexane diamine, and investigated how facial interactions and the positions of substituents determine the diastereoselectivity and geometry of the final assemblies.

Narcissistic chiral self-sorting prevailed in the assembly of molecular face-rotating polyhedra from a C3h building block 5,5,10,10,15,15-hexabutyl-truxene-2,7,12-tricarbaldehyde and racemic mixtures of 1,2-diamines. Out of 124 possible stereoisomers, a pair of racemic polyhedra dominated, wherein (1R,2R)-diamines were segregated in AAAA polyhedra and (1S,2S)-diamines in CCCC polyhedra. This chiral self-sorting process is regulated by facial non-covalent interactions in the polyhedra. In contrast, D3h facial building blocks 1,3,5-tris-(4-formyl-phenyl)triazine and racemic mixtures of 1,2-diamines assembled into polyhedra without facial interactions, and their assembly process did not undergo apparent chiral self-sorting.

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1β (IL-1β) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1β-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.

Our previous study (Oncotarget 2016; 7:46) demonstrated that the over-expression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line (a murine HCC cell with lymph node metastatic [LNM] rate of >75%) downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo. In current work, we investigated the effects of Sulf-1 knockdown on mesothelin (Msln) and it’s effects on the in vitro cell proliferation, migration, invasion, and in vivo tumor growth and LNM rate for Hca-P cells (a murine HCC cell with LNM rate of

Water-splitting devices for hydrogen generation through electrolysis (hydrogen evolution reaction, HER) hold great promise for clean energy. However, their practical application relies on the development of inexpensive and efficient catalysts to replace precious platinum catalysts. We previously reported that HER can be largely enhanced through finely tuning the energy level of molybdenum sulfide (MoS2) by hot electron injection from plasmonic gold nanoparticles. Under this inspiration, herein, we propose a strategy to improve the HER performance of MoS2 by engineering its energy level via direct transition-metal doping. We find that zinc-doped MoS2 (Zn-MoS2) exhibits superior electrochemical activity toward HER as evidenced by the positively shifted onset potential to -0.13 V vs RHE. A turnover of 15.44 s-1 at 300 mV overpotential is achieved, which by far exceeds the activity of MoS2 catalysts reported. The large enhancement can be attributed to the synergistic effect of electronic effect (energy level matching) and morphological effect (rich active sites) via thermodynamic and kinetic acceleration, respectively. This design opens up further opportunities for improving electrocatalysts by incorporating promoters, which broadens the understanding toward the optimization of electrocatalytic activity of these unique materials.

Anaerobic digestion is an attractive waste treatment technology, achieving both pollution control and energy recovery. Though the inhibition of polystyrene nanoplastics in anaerobic granular sludge is well studied, no direct evidence has been found on the interaction of methanogens and nanoplastics. In this study, to characterize the location of nanoplastics, Pd-doped polystyrene nanoplastics (Pd-PS) were used to explore the inhibition mechanism of anaerobic sludge through short-term exposure to Methanosarcina acetivorans C2A. The results showed that Pd-PS inhibited the methanogenesis of the anaerobic sludge, and the methane production decreased as the Pd-PS increased, with a 14.29% reduction at the Pd-PS concentration of 2.36 × 1010 particles/mL. Also, Pd-PS interacted with the protein in the extracellular polymeric substances (EPS). Furthermore, Pd-PS inhibited the methanogenesis of M. acetivorans C2A without exhibiting an evident reduction in the growth. The inhibition of Pd-PS on methane was due to the inhibition of methane production related genes, MtaA and mcrA. These results provide potential explication for the inhibition of nanoplastics on the methanogens, which will fulfill the knowledge on the stability of methanogens under the short-term exposure of nanoplastics.

We have previously demonstrated that transcriptionally active high-risk HPV (hr-HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway which are targets for the viral oncoproteins, E6/E7 respectively. Prospectively, BM(n=81)/BD(n=72)/OAC(n=65) FFPE specimens were subjected to IHC staining for pRb, p16INK4A, cyclin D1, p53 and RNA in-situ hybridization (ISH) for E6/E7 transcripts. HPV DNA was determined via PCR in fresh frozen specimens. Viral load measurement (real-time PCR) and Next Generation Sequencing of TP53 was also performed. Of 218 patients, 56 were HPV DNA positive [HPV16 (n=42), 18 (n=13), 6 (n=1)]. Viral load was low. Transcriptionally active HPV (DNA+/RNA+) was only found in the dysplastic and adenocarcinoma group (n=21). The majority of HPV DNA+/RNA+ BD/OAC were characterized by p16INK4Ahigh (14/21, 66.7%), pRblow (15/21, 71.4%) and p53low (20/21, 95%) and was significantly different to controls [combination of HPV DNA-/RNA- (n=94) and HPV DNA+/RNA- cohorts (n=22)]. p53low had the strongest association with DNA+/RNA+ oesophageal lesions (OR=23.5, 95% CI=2.94-187.8, p=0.0029). Seventeen HPV DNA+/RNA+ BD/OAC identified as p53low, were sequenced and all but one exhibited wild-type status. pRblow/p53low provided the best balance of strength of association (OR=8.0, 95% CI=2.6-25.0, p=0.0003) and sensitivity (71.4%)/specificity (71.6%) for DNA+/RNA+ BD/OAC. Active HPV involvement in BD/OAC is characterized by wild-type p53 and aberrations of the retinoblastoma protein pathway. This article is protected by copyright. All rights reserved.

To improve the aroma profile of Ecolly dry white wine, the simultaneous and sequential inoculations of selected Rhodotorula mucilaginosa and Saccharomyces cerevisiae were performed in wine making of this work. The two yeasts were mixed in various ratios for making the mixed inoculum. The amount of volatiles and aroma characteristics were determined the following year. Mixed fermentation improved both the varietal and fermentative aroma compound composition, especially that of (Z)-3-hexene-1-ol, nerol oxide, certain acetates and ethyls group compounds. Citrus, sweet fruit, acid fruit, berry, and floral aroma traits were enhanced by mixed fermentation; however, an animal note was introduced upon using higher amounts of R. mucilaginosa. Aroma traits were regressed with volatiles as observed by the partial least-square regression method. Analysis of correlation coefficients revealed that the aroma traits were the multiple interactions of volatile compounds, with the fermentative volatiles having more impact on aroma than varietal compounds.

We summarize nitrate transporters and discuss their potential in breeding for improved nitrogen use efficiency and yield.

In dicot root systems, lateral roots are in general regularly spaced along the longitudinal axis of the primary root to facilitate water and nutrient uptake. Recently, recurrent programmed cell death in the root cap of the growing root has been implicated in lateral root spacing. The root cap contains an auxin source that modulates lateral root patterning. Periodic release of auxin by dying root cap cells seems to trigger lateral root specification at regular intervals. However, it is currently unclear through which molecular mechanisms auxin restricts lateral root specification to specific cells along the longitudinal and radial axes of the root, or how environmental signals impact this process.

Osteoarthritis (OA) is the most common form of joint disease and is widespread in the elderly population and is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Oleuropein (OL), a secoiridoid, is considered as the most prevalent phenolic component in olive leaves and seeds, pulp and peel of unripe olives and has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of OL on human OA chondrocytes. Human OA chondrocytes were pretreated with OL (10, 50 and 100 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. The production of NO, PGE2, MMP-1, MMP-13, and ADAMTS-5 was evaluated by the Griess reaction and ELISA assays. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP13, ADAMTS-5, aggrecan, and collagen-II was measured by using real-time PCR. The protein expressions of COX-2, iNOS, p65, IκB-α, JNK, p-JNK, ERK, p-ERK, p38, and p-p38 were tested by using western blot. We found that OL significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-13, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, OL dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that OL could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. These results indicate that the therapeutic effect of OL on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Altogether, our findings provide the evidence to develop OL as a potential therapeutic agent for patients with OA.

A composite film of PMMA microspheres in PDMS is used as the fusion layer to avoid trapped air and to restrict the flow of the melted polymer during welding. The matrix material selection and distribution of PMMA microspheres is determined by the 1-D theoretical model. The theoretical work reveals that the difference in dynamic modulus between the matrix material and PMMA is the most significant contribution to the viability of this composite ultrasonic welding film. The experiment is conducted with PDMS as the matrix material to determine effect of the concentration of PMMA microspheres as micro energy directors on the welding strength and quality of the proposed methodology with the chosen composite. While there are no visible signs of trapped air in all specimens, the resultant welding strength in this methodology is limited by the particle size range of the PMMA microspheres. For ultrasonic energy input of 1 kJ on a 32 mm × 32 mm sample, the optimum concentration of PMMA microspheres is found to be 0.24.

A biological clock activated by oscillating signals, known as root clock, has been linked to lateral root (LR) formation and is essential for regular LR spacing along the primary root. However, it remains unclear how this internal mechanism is influenced by environmental factors known to affect the LR pattern. Here, we report that excessive cadmium (Cd) inhibits LR formation by disrupting the lateral root cap (LRC)-programmed cell death (PCD)-regulated root clock. Cd restricts the frequency of the oscillating signal rather than its amplitude. This could be attributed to the inhibition on meristematic activity by Cd, which resulted in decreased LRC cell number and LRC-PCD frequency. Genetic evidence further showed that LRC cell number is positively correlated with root resistance to Cd. Our study reveals root cap dynamics as a novel mechanism mediating root responses to Cd, providing insight into the signalling pathways of the root clock responding to environmental cues.

Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension-independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl-L-arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway. Following establishment of diabetic rat models, diabetes-related blood biochemical indices and cardiac function were measured in diabetic rats treated with lentivirus expressing DDAH2, short hairpin RNA against DDAH2, or L-NNA (inhibitor of NOS) to identify the roles of DDAH2 in DCM. The functional roles of DDAH2 in DCM were further determined through detection of the levels of collagen I, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). The H9C2 myocardial cell line was selected for in vitro experiments. The effects of DDAH2 on the migration of myocardial cells under high glucose conditions were also examined. To further investigate the underlying regulatory mechanism of DDAH2 in DCM, the contents of ADMA and NO, and the activities of DDAH and NOS were observed. The DCM model rats treated with DDAH2 exhibited reduced left ventricular end-diastolic pressure, and decreased blood glucose, total cholesterol, triglyceride, fasting blood glucose, and fasting insulin levels, but exhibited increased left ventricular systolic pressure and maximum rate of left ventricular pressure rise/fall levels in myocardial tissues. Myocardial cells under high glucose conditions treated with DDAH2 showed reductions in collagen I, MMP2 and TIMP2, indicating that DDAH2 reduced cell migration. Decreased levels of ADMA and NO but increased levels of DDAH and NOS were observed following treatment with DDAH2, indicating that the DDAH/ADMA/NOS/NO pathway was activated. These results reveal that the overexpression of DDAH2 attenuates myocardial fibrosis and protects against DCM through activation of the DDAH/ADMA/NOS/NO pathway in DCM rats. These results indicate that DDAH2 is a potential therapeutic candidate for the treatment of DCM.

High nitrogen (N) fertilization for maximizing crop yield commonly leads to postponed flowering time (heading date in rice) and ripening, thus affecting resources use efficiency and followed planting time. We found that N-mediated heading date-1 (Nhd1) can directly activate florigen gene OsHd3a in rice. Inactivation of either Nhd1 or OsHd3a results in delay and insensitivity to N supply of flowering time. Knockout of Nhd1 increases N uptake and utilization efficiency at low-to-moderate N level under both short- and long-day field conditions. Increasing glutamine, the product of N assimilation, can upregulate expression of Nhd1, which in turn downregulates OsFd-GOGAT expression and OsFd-GOGAT activity, displaying a Nhd1-controlled negative feedback regulatory pathway of N assimilation. Moreover, N fertilization effect on rice flowering time shows genetically controlled diversity, and single-nucleotide polymorphism in Nhd1 promoter may relate to different responses of flowering time to N application. Nhd1 thus balances flowering time and N use efficiency in addition to photoperiod in rice.

Plant HAK/KUP/KT family members function as plasma membrane (PM) H+/K+ symporters and may modulate chemiosmotically-driven polar auxin transport (PAT). Here, we show that inactivation of OsHAK5, a rice K+ transporter gene, decreased rootward and shootward PAT, tiller number, and the length of both lateral roots and root hairs, while OsHAK5 overexpression increased PAT, tiller number, and root hair length, irrespective of the K+ supply. Inhibitors of ATP-binding-cassette type-B transporters, NPA and BUM, abolished the OsHAK5-overexpression effect on PAT. The mechanistic basis of these changes included the OsHAK5-mediated decrease of transmembrane potential (depolarization), increase of extracellular pH, and increase of PM-ATPase activity. These findings highlight the dual roles of OsHAK5 in altering cellular chemiosmotic gradients (generated continuously by PM H+-ATPase) and regulating ATP-dependent auxin transport. Both functions may underlie the prominent effect of OsHAK5 on rice architecture, which may be exploited in the future to increase crop yield via genetic manipulations., The potassium transporter OsHAK5 in rice acts as a convergence point between the developmental pathways of tillering, lateral root and root-hair growth, and the auxin transport pathway. This study reveals dual roles of OsHAK5 in altering cellular chemiosmotic gradients (generated continuously by plasma membrane H+-ATPase) and regulating ATP-dependent auxin transport.

This article reviews spectral unmixing used as a new method for Raman imaging. Raman spectroscopy explores the vibrational information about specific chemical bonds in molecules, which can be used for label-free molecular visualization. However, chemical bonds are usually shared among different molecules, which results in closed or mixed Raman peaks of many molecules. Therefore, the acquired spectra cannot be directly used to reconstruct the Raman images, as pure component spectra are hidden under the acquired spectra. Spectral unmixing is an effective method to provide a meaningful spectrum of each component with no priori spectral information and to also reconstruct the compositional distribution images. This article summarizes some representative spectral unmixing approaches used for Raman imaging and many related researches. This review strives to introduce the combination of spectral unmixing and Raman imaging as an efficient analytic technique to characterize various constituents and make su...