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Dual-phase amorphous-nanocrystalline Al-x at.% Mo (x = 20, 26, 30) alloy films prepared in the way of dual-phase co-growth directly through magnetron sputtering were studied in terms of thermally induced microstructural evolution and mechanical properties via annealing at 550 °C. It was observed that, the annealed Al-26 and 30 at.% Mo alloy films maintained stable dual-phase amorphous-nanocrysatlline structure and precipitated Al8Mo3 nano-grains dispersed in amorphous matrix uniformly. After annealing, the surface roughness of Al-26 and 30 at.% Mo alloy films remained unchanged of 7.5 nm and the hardness and elastic modulus of them were as high as 13 and 210 GPa which enhanced about 50 % and 24 % than before, respectively. In contrast, the Al-20 at.% Mo alloy film crystallized completely and mainly contained intermetallic Al12Mo phase along with apparent grain coarsening after annealing, which resulted in significant increase of surface roughness and deterioration of hardness. The excellent thermal stability of dual-phase amorphous-nanocrystalline Al-26 and 30 at.% Mo alloy films stem from the small driving force for precipitated Al8Mo3 nano-grain growth, as well as benefit from effect of diffusion field impingement.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

The development of robust alloys capable of maintaining high strength and ductility at cryogenic temperatures has been a long-sought goal, particularly for load-bearing applications in extremely low-temperature environments. In this study, we reported a newly developed face-centered-cubic (FCC) metastable (Ni0·3Co0·4Cr0.3)94Mo6 medium-entropy alloy (Mo-MEA) with an excellent synergy of strength and ductility at 77 K, surpassing the toughest equiatomic NiCoCr MEA. Compared to the equiatomic NiCoCr MEA, the Mo-MEA exhibited a substantial increase in yield strength by 68 % (from 407 to 685 MPa) and a decent enhancement of the ultimate tensile strength by 10 % (from 1289 to 1415 MPa), along with a marginal increase in elongation from 75 % to 78.45 %. Electron backscatter diffraction and transmission electron microscopy revealed the activation of multimodal deformation mechanisms, including dislocations, stacking faults, twinning, and FCC-to-hexagonal-close-packed phase transformation, during the tensile deformation at 77 K.

In this paper, the environmental and economic indicators based on the reactive power pricing are proposed so as to formulate the novel environmental economic power dispatch (NEED) problems for electricity trading. Here, a new way of calculating total cost is proposed based on the reactive power pricing instead of the pure fuel cost, which leads to the NEED problems. In addition, an improved tunicate swarm algorithm (ITSA) is proposed to deal with the NEED problems. Different from the original tunicate swarm algorithm (TSA), adaptive weight parameter and mutation process are used to improve the disadvantages of TSA which converges too fast and easily falls into local optimum. In combination with the Pareto dominance rule, the ITSA can be more effective in dealing with the NEED problems. In order to examine the performance of the ITSA, simulation tests of ITSA, TSA, and particle swarm optimization (PSO) are conducted in IEEE30 node system. During the experimental process, optimized objective functions include total cost considering reactive cost, pollution emission and power loss. The final comparison results show that the ITSA is able to get better distributed Pareto front (PF) and superior best compromise solution (BCS), which proves the high efficiency of the ITSA in dealing with the NEED problems.

The utilization of herbal extraction residues (HERs) for production of valuable products has gained significant momentum in recent years. In this study, Lianhua Qingwen residue (LQR) was selected as a representative HER for enzymatic saccharification. By subjecting starch-containing raw unpretreated LQR to direct hydrolysis using a combination of cellulolytic and amylolytic enzyme, a glucan conversion of around 60 % was achieved within 48 h. To further enhance the hydrolysis rate and yield, ultrasound treatment of LQR samples was conducted. Investigation into the effect of ultrasound treatment on subsequent enzymatic saccharification revealed a noteworthy acceleration in the saccharification rate of LQR, exceeding 20 % within 10 h of hydrolysis time. Notably, this enhancement was achieved even when the substrate concentration was high at 10 % under optimized conditions of 5 min of sonication at a power intensity of 1.20 kW/cm2 and a temperature of 50 °C. The improvement in efficiency can be attributed to the disruptive effect of ultrasound treatment on the structure of LQR, leading to a reduction in particle size. Consequently, the LQR particles exhibited better contact with the enzyme, promoting a more efficient saccharification process. These findings suggest that ultrasound technology holds considerable potential for enhancing the enzymatic saccharification of HERs.

Population aging is a global problem, and improving the well-being of older adults is an urgent issue. Voice assistants (VAs) offer hands-free voice control and friendly human-computer interaction, making them a significant solution to address the aging problem. Most extant research on VAs is fragmented, and there are relatively few studies conducted from the perspective of emotional needs. This work proposes a comprehensive research model extending the technology acceptance model (TAM) by incorporating the influencing factors subordinate to two research directions: usability and emotional needs. Usability needs include three factors: perceived convenience, security/privacy, and Internet self-efficacy. Emotional needs include humanized interaction, perceived enjoyment, and perceived companionship. A structural equation model (SEM) was used to validate the model empirically with a sample of 425 older users of VAs. The analysis results are quite consistent with the research assumptions, and the findings illustrate that companionship is the most critical factor affecting older adults' intention to adopt VA use, which demonstrates the pivotal role of VAs in meeting the emotional needs of the elderly. The most unexpected observation was seen for the relationship between perceived ease of use and behavioral intention, which was non-significant. This result confirms that when a technology is perceived as very easy to use, perceived ease of use has little to no impact on individuals' intention to use that technology. The novelty of this study lies in the investigation of older adults' behavioral intentions toward using VAs, providing valuable insights for the design and development of VAs tailored for the elderly population. Beyond the academic realm, this research serves as direct inspiration for designers, developers, and policymakers in the fields of assistive technologies and geriatric care. It offers practical insights into creating VAs that effectively address the emotional needs of older adults and enhance their quality of life. Furthermore, elderly individuals are poised to experience significant benefits from the outcomes of this study，the insights garnered from this study empower the elderly to embrace technological advancements that align with their preferences and comfort levels. This study contributes to a more comprehensive understanding of VAs and their potential to enhance the well-being of older adults, while also paving the way for future investigations in this domain. As underscored by this study's emphasis on the significance of emotional needs in technology acceptance, it encourages the adoption of more user-centered design strategies in the development of future VAs.

The skeleton of 2-trifluoromethyl quinoline is the core structure of many natural products and pharmaceutical molecules. The synthesis of this scaffold is limited by metal catalysis, harsh conditions, toxic or hazardous reagents and solvents, and lower atom-economy. Herein, a novel method for the synthesis of 2-trifluoromethyl quinolines via the [4 + 2] cyclization of β-keto esters or 1,3-diketones with various substituted o-aminobenzaldehydes using the metal free catalyst in EtOH is reported. This atom- and step-economical protocol features simple operation, broad substrate scope, and good functional-group compatibility. The synthetic utility of this methodology was highlighted by easy gram-scale synthesis and late-stage functionalization, which would promote the vigorous development of quinoline chemistry. Moreover, the in vitro antifungal activities of the 2-trifluoromethyl quinolines against F. graminearum (from wheat), F. graminearum (from corn), F. moniliforme, F. oxysporum, and R. solani were investigated to further potential utility of these compounds.

In this study, colorimetric and antioxidant films were developed by using cassava starch (CS), κ-carrageenan (KC) and black nightshade fruit anthocyanins (BNA), and their physical and functional properties were investigated. We found BNA presented significant color changes in different pH solutions. And incorporation of BNA significantly increased the tensile strength, water vapor permeability, UV–vis light barrier property, pH-sensitivity and antioxidant activity of CS-KC film. Results of structural characterization indicated that H-bonds were formed between CS, KC and BNA in films and the film compactness was significantly improved by BNA incorporation. Results of the rheological property assay showed the films had high apparent viscosity with an obvious shear-thinning behavior. When applied to monitoring the quality change of Cyclina sinensis, CS-KC-BNA films exhibited significant color changes with the degradation process of C. sinensis qualities. Our results suggested CS-KC-BNA films could be utilized in smart packaging in food industry.

Objective: Body weight change and obesity follow the variance of excess energy input balanced against tightly controlled EE (energy expenditure). Since insulin resistance can reduce energy storage, we investigated whether genetic disruption of hepatic insulin signaling reduced adipose mass with increased EE. Methods: Insulin signaling was disrupted by genetic inactivation of Irs1 (Insulin receptor substrate 1) and Irs2 in hepatocytes of LDKO mice (Irs1L/L·Irs2L/L·CreAlb), creating a state of complete hepatic insulin resistance. We inactivated FoxO1 or the FoxO1-regulated hepatokine Fst (Follistatin) in the liver of LDKO mice by intercrossing LDKO mice with FoxO1L/L or FstL/L mice. We used DEXA (dual-energy X-ray absorptiometry) to assess total lean mass, fat mass and fat percentage, and metabolic cages to measure EE (energy expenditure) and estimate basal metabolic rate (BMR). High-fat diet was used to induce obesity. Results: Hepatic disruption of Irs1 and Irs2 (LDKO mice) attenuated HFD (high-fat diet)-induced obesity and increased whole-body EE in a FoxO1-dependent manner. Hepatic disruption of the FoxO1-regulated hepatokine Fst normalized EE in LDKO mice and restored adipose mass during HFD consumption; moreover, hepatic Fst disruption alone increased fat mass accumulation, whereas hepatic overexpression of Fst reduced HFD-induced obesity. Excess circulating Fst in overexpressing mice neutralized Mstn (Myostatin), activating mTORC1-promoted pathways of nutrient uptake and EE in skeletal muscle. Similar to Fst overexpression, direct activation of muscle mTORC1 also reduced adipose mass. Conclusions: Thus, complete hepatic insulin resistance in LDKO mice fed a HFD revealed Fst-mediated communication between the liver and muscle, which might go unnoticed during ordinary hepatic insulin resistance as a mechanism to increase muscle EE and constrain obesity.

An environmentally benign highly atom-economic protocol for the construction of the CC bond has been developed under catalyst- and solvent-free conditions. This protocol involves the efficient coupling of 2-methyl quinazolinones with 3-(trifluoroacetyl)coumarins for the access of quinazolinone derivatives in excellent yields (up to 90 %). The crystal structure of compound 3di was investigated by X-ray diffraction analysis. The biological activities, such as in vitro antifungal activity of the quinazolinone derivatives against Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum, Phytophthora parasitica var nicotianae, and Rhizoctonia solani Kuhn, were investigated. The bioassay results indicated that most of the target products exhibited promising fungicidal activities, and compound 3 cl exhibited 95 % fungicidal activity against R. solani, with an EC50 value of 10.6 μg/mL.

Many crystals in nature have simple interatomic microstructures, such as simple cubic (SC), body-centered cubic (BCC), and face-centered cubic (FCC) lattice symmetries, making these structures extremely stable. Inspired by these arrangements, a series of architected micro-channel heat exchangers with rationally designed 3D microstructures were established. A multi-physics mathematical model using thermal-fluid-structure interaction (TFSI) was employed to investigate the coupled heat transfer performance and mechanical properties of these architected heat exchangers. When compared with the corrugated straight plate (CSP) microchannel heat exchanger, the thermal-hydraulic performance factors (TPC) of FCC and BCC microchannel heat transfer were 2.20 and 1.70 times that of SC microchannel heat exchanger, respectively. The micro-channel heat exchanger with FCC architectures could enhance the convective heat transfer performance by 201.0%, while the micro-channel heat exchanger with SC architectures reduced the Von-Mises equivalent (VME) stress by 20.0% when compared with the conventional 2D CSP heat exchanger. The proposed architected micro-channel heat exchangers could find a wide range of potential applications ranging from power electronics in electric vehicles to concentrated solar power systems, where both good convective heat transfer performance and high mechanical strength are simultaneously pursued.

A one-pot two-step reaction of 2-(trifluoromethyl)-2-hydroxy-2H-chromene with aryl ketone afforded α-trifluoromethylated tertiary alcohols bearing coumarins. The atomic economic and simply manipulative reaction involved premier treatment of reaction mixtures with CH3COOH and NH4OAc in one-pot process. The reaction proceeded to give the title compounds in moderate to good yields.

Nasal administration of Traditional Chinese medicine (TCM) has a long history of applications. With the gradual maturing of technology and pharmacological advances, nasal preparations of TCM have undergone significant changes. Nasal TCM formulations are used not only for treatment of pneumonia, asthma, sinusitis and allergic rhinitis but also Alzheimer's disease and Parkinson's disease, as antidepressants and antiepileptics, and in ischemia reperfusion. However, according to the analysis of nasal preparations of TCM currently on the market, most of them were compound preparations, which were used to treat allergic rhinitis (AR), common cold, headache and other local treatments, with a small range of diseases. At the same time, the dosage forms were mainly traditional dosage forms, aerosols and sprays, but there were no new dosage forms, which can not meet the clinical needs in terms of variety number, variety diversity and disease types. In this manuscript, we reviewed the development and applications of different nasal preparations of TCM from the aspects of nasal structure, origin, factors affecting absorption and common dosage forms, pharmacodynamics, targeting of nasal delivery and safety. In the near future, we expect that more nasal preparations of Chinese medicine with independent intellectual property rights will be marketed to meet the needs of clinical disease management.

Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered para-cyclophane ether. Herein, we identified new xenoacremones A, B, and C (1−3) from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans. The hybrid polyketide synthase–nonribosomal peptide synthetase (PKS−NRPS) XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton. This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety. XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system. Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether, which underwent subsequent spontaneous Diels−Alder reaction to give the end products. Thus, the results indicated that three novel enzymes XenF, XenD, and XenC coordinate to assemble the [6.5.6] tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.

A series of novel 1-(β-coumarinyl)-1-(β-indolyl)-1-(α-thiophenyl)trifluoroethane derivatives 5aaa-5hdb were prepared by one-pot reaction from 3-(trifluoroacetyl)coumarin with indole and α-substituted thiophene. Their structures were confirmed by 1H NMR, 13C NMR, 19F NMR, HRMS and X-ray single crystal diffraction, and their antifungal activities against F. moniliforme, F. graminearum, F. oxysporum, R. solani and P. nicotianae were evaluated. The title compounds displayed significant to moderate in vitro antifungal activity when compared to the standard drug triadimefon. Among the synthesized compounds, compound 5bfa showed the highest inhibitor rate of 83.5 % at 0.500 mg/mL against R. solani, while compound 5ada displayed the highest inhibitor rate of 73.3 % at 0.500 mg/mL against F. graminearum.

Summary: The dynamic interaction between the CMV virus and host immune response remains obscure, thus hindering the diagnosis and therapeutic management of patients with HSCT. The current diagnosis of CMV viremia depends on viral load estimation. Medical intervention based on viral load, can be unnecessary or poorly timed for many patients. Here we examined the clinical features and blood samples of patients with HSCT and assessed the CMV reactivation kinetics and corresponding CMV antigen-specific T-cell response in individual patients based on a peptide pool stimulation T-cell assay, which showed that CMV-specific CD8+ T cells were more suitable to be a diagnosis indicator for suppressing CMV reactivation. Using ROC analysis, we defined and verified a CMV-specific CD8+ T-cell counts threshold (925 cells/106 PBMCs) as an indicator of CMV reactivation post-HSCT, and suggested that use of this threshold would provide more accurate guidance for prompt medication and better management of CMV infection post-HSCT.

Anthropogenic source of heavy metals in the estuary-coastal sediment could cause serious environmental concerns. Thus, much needs to be concerned about the linkages between bacterial community, microbial nitrogen processes and heavy metals accumulation in the ocean tidal flush urban estuary where the river meet the sea. In this study, Illumina sequencing analysis and quantitative PCR (qPCR) were adopted to detect the effect of heavy metals on the bacterial community and nitrogen transformation genes from vertical sediment profiles in the four tidal flush estuaries. Results indicated that bacterial community and structure varied greatly from the vertical and spatial distribution. The vertical distribution of heavy metals varied greatly in the different groups. It was concluded that the accumulation of heavy metals mainly occurred in the medium layer of the depth from 40 cm to 70 cm. Heavy metals were found to pose a significant influence on the bacterial community and nitrogen transformation genes. The abundance of denitrification genes was highly associated with Cr, Zn, As and the abundance of amoA was vulnerable to the influence of Ni. Both denitrification and nitrification genes were greatly affected by C and N content, which indicated that the enhanced nitrogen transformation activities mainly occurred in the top layer sediment. Our results indicated that the bacterial community and nitrogen transformation functional genes were sensitive to the variation of heavy metals and nutrient content, which will provide new insight into the microbial N-cycling process influenced by pollutant and show a potential strategy for discharge management in the circumstances of estuary-coastal zones.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease. Aiming at assessing the effect of total saponins from American ginseng on COPD, both the chemical composition and anti-COPD activity of total saponins from wild-simulated American ginseng (TSW) and field-grown American ginseng (TSF) were investigated in this study. Firstly, a HPLC-ELSD chromatographic method was established to simultaneously determine the contents of 22 saponins in TSW and TSF. Secondly, CS-induced COPD mouse model was established to evaluate the activity of TSW and TSF. The results indicated that both TSW and TSF had the protective effect against COPD by alleviating oxidative stress and inflammatory response. TSW showed a stronger effect than TSF. Thirdly, an integrated approach involving metabolomics and network pharmacology was used to construct the ''biomarker-reaction-enzyme-target'' correlation network aiming at further exploring the observed effects. As the results, 15 biomarkers, 9 targets and 5 pathways were identified to play vital roles in the treatment of TSW and TSF on COPD. Fourthly, based on network pharmacology and the CS-stimulated A549 cell model, ginsenoside Rgl, Rc, oleanolic acid, notoginsenoside R1, Fe, silphioside B were certified to be the material basis for the stronger effect of TSW than TSF. Finally, the molecular docking were performed to visualize the binding modes. Our findings suggested that both TSW and TSF could effectively ameliorate the progression of COPD and might be used for the treatment of COPD.

A versatile and environmentally friendly method for the synthesis of various organophosphorus compounds have been developed under microware conditions. We have synthesized a series of the trifluoromethyl phosphonates via Phospha-Brook rearrangement between dialkylphosphite and 3-(trifluoroacetyl)coumarins using KF/Al2O3 as a highly efficient solid catalyst under solventless conditions. Catalyst reuse, ease of separation of the pure product, and high yields are some of the unique features of this process. In addition, the mycelial growth rate method was used to examine the in vitro antifungal activities of the phosphates 4a-o against Phytophthora capsici, Fusarium oxysporum vasinfectum, Bipolaris maydis and Alternaria solani at 500 µg/mL. The results showed that compound 4n exhibited significant anti-Phytophthora capsici activity with inhibitory index of 86%.

A series of novel coumarin thiazoles containing trifluoromethyl group 3a-3l were prepared through a one-pot reaction using 3-(trifluoroacetyl)coumarin as a starting material in solvent-free conditions. Their structures were confirmed using IR, 1H NMR, 13C NMR, HRMS and X-ray single crystal diffraction, and their antifungal activity against Fusarium. moniliforme(F. moniliforme), Fusarium. graminearum (F. graminearum), and Curvularia. lunata (C. lunata) was evaluated. Among the synthesized compounds, compound 3f showed the highest inhibitor rate of 74% at 0.5 mg/mL against F. moniliforme, and compound 3g exhibited the highest inhibitor rates of 89% and 93.4% at 0.5 mg/mL against F. graminearum and C. lunata, respectively. The introduction of trifluoromethyl group greatly improved the antifungal activity of counterpart 3g compared to the compound 4.

Heart failure (HF), with a high fatality rate, is seriously harmful to human health. Ginsenoside Rg5 (Rg5) is the major active component in black ginseng. The effect and mechanism of Rg5 on HF were investigated for the first time. Firstly, the in vitro angiotensin-converting enzyme (ACE) inhibitory activity was evaluated. Then, the verapamil-induced zebrafish HF model was used to assay the effect of Rg5. Finally, the untargeted metabolomics based on UPLC-QTOF-MS was applied to explore the latent mechanism by analyzing the metabolic perturbation. The results showed that Rg5 had a similar ACE-inhibitory activity (IC50 = 0.124 μM) to the reference drug enalapril. Rg5 could dramatically improve cardiac function in a dose-dependent manner. A total of 22 differentiated metabolites and 8 perturbed metabolic pathways were identified. In summary, this study indicated that Rg5 could be a potential agent for protecting heart function in the clinical treatment of heart failure.

Summary: The plant galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) have been linked to the anti-inflammatory and cancer benefits of a green leafy vegetable diet in humans due to their ability to regulate the levels of free radicals like nitric oxide (NO). Here, we show that DGDG contributes to plant NO as well as salicylic acid biosynthesis and is required for the induction of systemic acquired resistance (SAR). In contrast, MGDG regulates the biosynthesis of the SAR signals azelaic acid (AzA) and glycerol-3-phosphate (G3P) that function downstream of NO. Interestingly, DGDG is also required for AzA-induced SAR, but MGDG is not. Notably, transgenic expression of a bacterial glucosyltransferase is unable to restore SAR in dgd1 plants even though it does rescue their morphological and fatty acid phenotypes. These results suggest that MGDG and DGDG are required at distinct steps and function exclusively in their individual roles during the induction of SAR. : The galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) constitute ∼80% of total membrane lipids in plants. Gao et al. now show that these galactolipids function nonredundantly to regulate systemic acquired resistance (SAR). Furthermore, they show that the terminal galactose on the α-galactose-β-galactose head group of DGDG is critical for SAR.

Summary: Systemic acquired resistance (SAR) is a form of resistance that protects plants against a broad spectrum of secondary infections. However, exploiting SAR for the protection of agriculturally important plants warrants a thorough investigation of the mutual interrelationships among the various signals that mediate SAR. Here, we show that nitric oxide (NO) and reactive oxygen species (ROS) serve as inducers of SAR in a concentration-dependent manner. Thus, genetic mutations that either inhibit NO/ROS production or increase NO accumulation (e.g., a mutation in S-nitrosoglutathione reductase [GSNOR]) abrogate SAR. Different ROS function additively to generate the fatty-acid-derived azelaic acid (AzA), which in turn induces production of the SAR inducer glycerol-3-phosphate (G3P). Notably, this NO/ROS→AzA→G3P-induced signaling functions in parallel with salicylic acid-derived signaling. We propose that the parallel operation of NO/ROS and SA pathways facilitates coordinated regulation in order to ensure optimal induction of SAR. : Nitric oxide (NO) and reactive oxygen species (ROS) serve as signaling molecules in diverse organisms. Here, Wang et al. show that NO and ROS also serve as inducers of systemic acquired resistance (SAR), an important form of broad-spectrum immunity in plants. Their results suggest that NO and ROS act in a concentration-dependent manner and in parallel with salicylic-acid-derived signaling to induce SAR. NO and ROS act as upstream signals in the pathway that includes azelaic acid, glycerol-3-phosphate, and the lipid-transfer-like proteins DIR1/AZI1.

Plant viruses often encode suppressors of host RNA silencing machinery, which occasionally function as avirulence factors that are recognized by host resistance (R) proteins. For example, the Arabidopsis R protein, hypersensitive response to TCV (HRT), recognizes the turnip crinkle virus (TCV) coat protein (CP). HRT-mediated resistance requires the RNA-silencing component double-stranded RNA-binding protein 4 (DRB4) even though it neither is associated with the accumulation of TCV-specific small RNA nor requires the RNA silencing suppressor function of CP. HRT interacts with the cytosolic fraction of DRB4. Interestingly, TCV infection both increases the cytosolic DRB4 pool and inhibits the HRT-DRB4 interaction. The virulent R8A CP derivative, which induces a subset of HRT-derived responses, also disrupts this interaction. The differential localization of DRB4 in the presence of wild-type and R8A CP implies the importance of subcellular compartmentalization of DRB4. The requirement of DRB4 in resistance to bacterial infection suggests a universal role in R-mediated defense signaling.

Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA) requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P). Pathogen inoculation induced the release of free unsaturated fatty acids (FAs) and thereby triggered AA accumulation, because these FAs serve as precursors for AA. AA accumulation in turn increased the levels of G3P, which is required for AA-conferred SAR. The lipid transfer proteins DIR1 and AZI1, both of which are required for G3P- and AA-induced SAR, were essential for G3P accumulation. Conversely, reduced G3P resulted in decreased AZI1 and DIR1 transcription. Our results demonstrate that an intricate feedback regulatory loop among G3P, DIR1, and AZI1 regulates SAR and that AA functions upstream of G3P in this pathway.