Lenvatinib targets STAT-1 to enhance the M1 polarization of TAMs during hepatocellular carcinoma progression.

Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.

Self-Lubrication Mechanism of Surface-Textured Polymer-Matrix Composites under the Induction of Frictional Stress.

Polymer-matrix composites have been widely used in the manufacture of seals, bearings, electrical insulators, and self-lubricating films as engineering applications move toward lighter weight, higher strength, and corrosion resistance. However, the high-speed shear effect of the friction pairs in relative motion leads to localized heating of the polymer surface, resulting in deformation or softening of the device. Herein, acer mono maple and canna leaves were used as templates to construct polymer-matrix sulfonated polyether-etherketone/polytetrafluoro-wax (SPEEK/PFW) composites with a surface-textured structure. As the bionic texture reduces the level of direct contact between the friction pairs, the frictional thermosoftening of SPEEK occurs in the localized areas of the bumps and leads to the release of PFW stored in textures, resulting in the formation of a soft polymer sliding layer in the worn area and greatly enhancing the frictional stability. By investigation of the tribological properties of textured SPEEK/PFW composites under different loads and sliding speeds, the mechanisms from surface wear to matrix softening and spontaneous construction of a slipping layer are summarized. The results of scanning electron microscopy and three-dimensional profilometer characterization of the wear scars show the surface state of SPEEK/PFW after friction, revealing the friction-thermotropic deformation of the surface texture. The results of this study not only improve our understanding of the frictional heat-induced surface self-lubrication mechanism of textured polymer composites but also provide a reference for the development of multiphase hybrid polymer-matrix composites with excellent self-lubrication properties.

Generating carbyne equivalents with photoredox catalysis.

Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species-carbocations, carbanions, radicals and carbenes-that is fundamental to our understanding of chemical reactivity. In contrast, the carbyne-a monovalent carbon with three non-bonded electrons-is a relatively unexplored reactive intermediate; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an 'assembly point' disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon-hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon-hydrogen bonds, while complementing current translational late-stage functionalization processes. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.

Generating Fischer-Type Rh-Carbenes with Rh-Carbynoids.

We describe the first catalytic generation of Fischer-type acyloxy Rh(II)-carbenes from carboxylic acids and Rh(II)-carbynoids. This novel class of transient donor/acceptor Rh(II)-carbenes evolved through a cyclopropanation process providing access to densely functionalized cyclopropyl-fused lactones with excellent diastereoselectivity. DFT calculations allowed the analysis of the properties of Rh(II)-carbynoids and acyloxy Rh(II)-carbenes as well as the characterization of the mechanism.

Recent Advances in Ynenamine Chemistry.

Enamines are formed by reacting a carbonyl compound with an amine under dehydration conditions. A vast array of transformations has been achieved via preformed enamine chemistry. Recently, by introducing conjugating double bonds to the enamine functionality, dienamines, and trienamines have propelled the discovery of several previously unattainable remote-site functionalization reactions of carbonyl compounds. Comparatively, alkyne-conjugating enamine analogues have recently shown high potential in multifunctionalization reactions while remaining underexplored. In this account, we systematically summarized and discussed recent advances in synthetic transformations based on ynenamine-containing compounds.

Neoadjuvant alectinib in locally advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement: case series and literature review.

In view of the success of targeted therapy in the field of advanced lung cancer, it is gradually pushed further to neoadjuvant therapy. Alectinib has been recommended for advanced anaplastic lymphoma kinase (ALK) + non-small cell lung cancer (NSCLC) in first-line therapy. Here, we report two cases of neoadjuvant alectinib in locally advanced lung adenocarcinoma with ALK rearrangement. Case 1 was a 64-year-old man with no history of smoking who was diagnosed with the clinical stage as IIIB, with ALK fusion-positive. Chest-enhanced computed tomography (CT) revealed marked regression and achieved partial response (PR) incorporated with grade 3 interstitial pneumonia after 44 days of alectinib neoadjuvant therapy. Interstitial pneumonia improved after methylprednisolone therapy, then thoracoscopic lobe resection with lymph node dissection was performed with blood loss. The pathological assessment was a pathologic complete response(pCR). Case 2 was a 66-year-old man who had a routine physical examination and then diagnosed with a clinical-stage IIIB by CT-guided percutaneous cutting needle biopsy (PCNB). Chemotherapy with 1 cycle of pemetrexed combined with nedaplatin was performed in the interval waiting for next-generation sequencing (NGS) results. NGS testing revealed an EML4-ALK fusion mutation. After 109 days of alectinib treatment, radiographic evaluation was classified as PR and then he underwent thoracoscopic upper lobectomy smoothly with pathological assessment as a major pathological response (MPR). To date, neoadjuvant alectinib has only been reported in a few cases in locally advanced lung adenocarcinoma with ALK-rearranged. Neoadjuvant alectinib may be feasible in locally advanced disease for complete resection. The duration and safety of neoadjuvant therapy with alectinib still need further study.

Copper stress-induced phytotoxicity associated with photosynthetic characteristics and lignin metabolism in wheat seedlings.

Copper (Cu) pollution is one of environmental problems that adversely affects the growth and development of plants. However, knowledge of lignin metabolism associated with Cu-induced phytotoxicity mechanism is insufficient. The objective of this study was to reveal the mechanisms underlying Cu-induced phytotoxicity by evaluating changes in the photosynthetic characteristics and lignin metabolism in the seedlings of wheat cultivar 'Longchun 30'. Treatment with varying concentrations of Cu clearly retarded seedling growth, as demonstrated by a reduction in the growth parameters. Cu exposure reduced the photosynthetic pigment content, gas exchange parameters, and chlorophyll fluorescence parameters, including the maximum photosynthetic efficiency, potential efficiency of photosystem II (PS II), photochemical efficiency of PS II in light, photochemical quenching, actual photochemical efficiency, quantum yield of PS II electron transport, and electron transport rate, but notably increased the nonphotochemical quenching and quantum yield of regulatory energy dissipation. Additionally, a significant increase was observed in the amount of cell wall lignin in wheat leaves and roots under Cu exposure. This increase was positively associated with the up-regulation of enzymes related to lignin synthesis, such as phenylalanine ammonia-lyase, 4-coumarate:CoA ligase, cinnamyl alcohol dehydrogenase, laccase, cell wall bound (CW-bound) guaiacol peroxidase, and CW-bound conifer alcohol peroxidase, and TaPAL, Ta4CL, TaCAD, and TaLAC expression. Correlation analysis revealed that lignin levels in the cell wall were negatively correlated with the growth of wheat leaves and roots. Taken together, Cu exposure inhibited photosynthesis in wheat seedlings, resulting from a reduction in photosynthetic pigment content, light energy conversion, and photosynthetic electron transport in the leaves of Cu-stressed seedlings, and the Cu-inhibitory effect on seedling growth was related to the inhibition of photosynthesis and an increase in cell wall lignification.

Long-term grazing improved soil chemical properties and benefited community traits under climatic influence in an alpine typical steppe.

Grazing and climate change both contribute to diversity loss and productivity fluctuations. Sensitive climate conditions and long-term grazing activities have a profound influence on community change, particularly in high-altitude mountain grassland ecosystems. However, knowledge about the role of long-term continuous grazing management on diversity, productivity and the regulation mechanisms in fragile grassland ecosystems is still rudimentary. We conducted a long-term grazing experiment on an alpine typical steppe in the Qilian Mountains to assess effects of grazing intensity on soil, diversity, productivity and the regulation mechanisms. Plants and soil were sampled along grazing gradients at different distances from the pasture entrance (0, 0.3, 0.6, 0.9, 1.2 and 1.5 km) under the non-growing (WP) and the growing season grazing pasture (SAP). The results revealed that community diversity and biomass did not change significantly on a time scale, while the concentration of soil organic carbon and total phosphorus increased significantly. Heavy grazing (0-0.3 km) decreased community diversity and biomass. Grazing increased soil chemical properties in heavy grazed areas of WP, while the opposite was recorded in SAP. Soil chemical properties explained the largest variances in community diversity and community biomass. The prediction model indicates that grazing in WP mainly affects community diversity through soil chemical properties, and promotes a positive correlation between community diversity and community biomass; in SAP, the direct effect of grazing gradients on community diversity and biomass is the main pathway, but not eliminating the single positive relationship between diversity and biomass, which means that diversity can still be used as a potential resource to promote productivity improvement. Therefore, we should focus on the regulation of soil chemical properties in WP, such as the health and quality of soil, strengthening its ability to store water, sequester carbon and increase nutrients; focus on the management of livestock in SAP, including providing fertilizer and sowing to increase diversity and production in heavily grazed regions and reducing grazing pressure through regional rotational grazing. Ultimately, we call for strengthening the stability and sustainability of ecosystems through targeted and active human intervention in ecologically sensitive areas to cope with future grazing pressures and climate disturbances.

A Carbene Relay Strategy for Cascade Insertion Reactions.

Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α-heteroatoms to carbonyl compounds. Nevertheless, the limited availability of carbene precursors restricts the introduction of only a single heteroatom. In this report, we describe a new approach based on an I(III) /S(VI) reagent that promotes the cascade insertion of heteroatoms. This is achieved by sequentially generating two α-heteroatom-substituted metal carbenes in one reaction. We found that this mixed I(III) /S(VI) ylide reacts efficiently with a transition metal catalyst and an X-H bond (where X=O, N). This transformation leads to the sequential formation of a sulfoxonium- and an X-substituted Rh-carbenes, enabling further reactions with another Y-H bond. Remarkably, a wide range of symmetrical and unsymmetrical α,α-O,O-, α,α-O,N-, and α,α-N,N-subsituted ketones can be prepared under mild ambient conditions. In addition, we successfully demonstrated other cascades, such as CN/CN double amidation, C-H/C-S double insertion, and C-S/Y-H double insertion (where Y=S, N, O, C). Notably, the latter two cascades enabled the simultaneous installation of three functional groups to the α-carbon of carbonyl compounds in a single step. These reactions demonstrate the versatility of our approach, allowing for the synthesis of ketones and esters with multiple α-heteroatoms using a common precursor.

Comparison between immunotherapy efficacy in early non-small cell lung cancer and advanced non-small cell lung cancer: a systematic review.

BACKGROUND: Currently, immunotherapy is widely used in the treatment of various stages of non-small cell lung cancer. According to clinical experience and results of previous studies, immunotherapy as neoadjuvant therapy seems to exhibit better efficacy against early resectable non-small cell lung cancer as compared to advanced lung cancer, which is often defined as unresectable non-small cell lung cancer. However, this observation has not been established in clinical studies. This systematic review aimed to evaluate the efficacy of immunotherapy in early and late lung cancer, wherein objective response rate (ORR) and disease control rate (DCR) were used as evaluation indexes. The present study also evaluated the safety of immunotherapy in early and late lung cancer, wherein the rate of treatment-related adverse reactions (TRAEs) was used as an indicator. METHODS: Electronica databases, including PubMed, Cochrane Library, Embase, and other databases, were searched to identify relevant studies. Besides this, all the available reviews, abstracts, and meeting reports from the main international lung cancer meetings were searched manually. ORR, DCR, and TRAEs were extracted as the primary outcomes. RESULTS: A total of 52 randomized controlled trials involving 13,660 patients were shortlisted. It was observed that immunotherapy alone significantly improved DCR in early lung cancer in comparison to advanced lung cancer. Importantly, the improvement in ORR was not to the same extent as reported in the case of advanced lung cancer. The combination of immunotherapy with other therapies, especially immunochemotherapy, significantly improved ORR and DCR in early lung cancer. In terms of safety, immunotherapy either alone or in combination with other therapies exhibited a better safety profile in early lung cancer than in advanced lung cancer. CONCLUSIONS: Altogether, the benefits of immunotherapy in early lung cancer appeared to be better than those observed in advanced lung cancer, especially with the regard to the regimen of immunotherapy in combination with chemotherapy. In terms of safety, both immunotherapy alone and its combination with chemotherapy were found to be safer in early lung cancer as compared to advanced lung cancer.

Ecological thresholds of toxic plants for sheep production and ecosystem multifunctionality and their trade-off in an alpine meadow.

Toxic plants are a natural component of alpine meadow which co-evolved with Tibetan sheep for thousands of years. One challenge for indigenous herders is to know the ecological thresholds of toxic plants and maintain their vital functions in ways that are compatible with economic income and ecological conservation. To achieve this, field trials with Tibetan sheep grazing in alpine meadow were conducted to examine the ecological thresholds of toxic plants for sheep production and ecosystem functions and their trade-offs. Our results demonstrated that the changing point values of biomass proportion of toxic plants for dry matter intake and liveweight gain of sheep were 17% and 22%, respectively. The changing point value of biomass (richness) proportion of toxic plants for soil carbon accumulation index was 31% (59%), for soil nutrient cycling index was 38% (42%), and for ecosystem multifunctionality index was 28% (50%). The trade-off between liveweight gain of sheep and ecosystem multifunctionality first decreased and then increased along the gradient of biomass proportion of toxic plants (the value of changing point was 37%), and had a significant negative correlation with richness of toxic plants. In addition, structural equation modeling indicated that toxic plants can affect the trade-off between liveweight gain of sheep and ecosystem multifunctionality though increasing acid detergent fiber of plant and decreasing plant species richness, belowground biomass and soil total phosphorus. Consequently, opinions towards toxic plants should shift from the conventional view that they are serious threat to grassland ecosystem health to an inclusive understanding that they are beneficial to livestock and ecosystem functions under certain ecological thresholds.

Selenium supplementation improves nutrient intake and digestibility, and mitigates CH4 emissions from sheep grazed on the mixed pasture of alfalfa and tall fescue.

Low selenium (Se) in soil and forage can adversely affect on the quality of animal-derived foods, and hence on human health. Lambs grazed on mixed pastures of alfalfa (Medicago sativa) and tall fescue (Festuca arundinacea) were supplemented with five levels of Se [0, 3, 6, 9 and 12 µg/kg body weight (BW)]. The intake of dry matter (DM) and organic matter (OM) varied with the level of Se supplementation, with a peak at 6 µg Se per kg BW (p ≤ 0.05). Gross energy (GE) intake, digestive energy (DE) intake and metabolic energy (ME) intake were higher at 6 µg Se per kg BW than at other Se levels (p < 0.01); in addition, methane energy (CH4 -E) output was lower at 6 µg Se per kg BW. Supplementation with Se significantly increased nitrogen (N) intake, faecal N and urine N, for which the peak values were 20.2 g N/, 5.62 g N/day and 7.92 g N/day, respectively, at 6 µg Se per kg BW. Se intake, blood Se, faecal Se, urine Se and retained Se were negatively correlated with forage crude protein (CP) content (p < 0.001) but were positively correlated with the content of neutral detergent fibre (NDF) (p < 0.001) and acid detergent fibre (ADF) (p < 0.001). Thus, we recommend the addition of 6 µg Se per kg BW to sheep grazed on pastures in regions with low soil Se.

ß-Diazocarbonyl Compounds: Synthesis and their Rh(II)-Catalyzed 1,3 C-H Insertions.

Herein, we describe the first electrophilic diazomethylation of ketone silyl enol ethers with diazomethyl-substituted hypervalent iodine reagents that gives access to unusual ß-diazocarbonyl compounds. The potential of this unexplored class of diazo compounds for the development of new reactions was demonstrated by the discovery of a rare Rh-catalyzed intramolecular 1,3 C-H carbene insertion that led to complex cyclopropanes with excellent stereocontrol.

Relationship of mineral elements in sheep grazing in the highland agro-ecosystem.

Objective: Minerals are one of the important nutrients for supporting the growth of sheep grazing in the highland, northeast of China. The experiment was conducted to investigate the relationship of both macro and micro minerals in sheep grazing in the highlands of six districts located in the Qilian Mountain of China. Methods: Samples of herbage (n=240) and soil (n=240) were collected at random in a "W" shape across the area designated for harvesting from 24 farms, where the sheep commonly graze in October (winter) for mineral analyses. In addition, serum samples were taken via jugular vein from 20 sheep per farm from 24 farms (n=480 samples in total) for serum minerals analyses. Mean values of macro and micro minerals were statistically compared among districts and the correlations among soil-plant-animal were statistically analyzed and correlations were regressed, as well. Results: The results revealed that there were variations for both macro and micro minerals among districts. Statistical analysis of the correlation coefficients between herbage and sheep were significantly different for most of the minerals but not for P, Cu, and Se. Many correlation regression coefficients were found significantly different among minerals of herbage, soil, and sheep serum especially those of K, Na, Fe, Mn, and Zn (between herbage and sheep serum), and Fe and Mn (between herbage and soil), Na, Fe, Mn, and Zn (between soil and sheep serum), respectively. The regression coefficient equations derived under this experiment for prediction of Ca (R2=0.618), K (R2=0.803), Mg (R2=0.767), Na (R2=0.670), Fe (R2=0.865), Zn (R2=0.950), Mn (R2=0.936), and Se (R2=0.630), resulted in significant R2 values. Conclusion: It is inferred that the winter herbage minerals in all the districts were below the recommended levels for macro minerals which indicated there would be some mineral deficiencies in sheep grazing the herbage in these regions. Supplemental minerals may therefore play an important role in balancing the minerals available from the herbage in winter and would lead to increased productivity in sheep on the highland areas of China. These findings could be potentially applied to the other regions for improving the livestock productivity.

Catalytic Cleavage of C(sp2)-C(sp2) Bonds with Rh-Carbynoids.

We report a catalytic strategy that generates rhodium-carbynoids by selective diazo activation of designed carbyne sources. We found that rhodium-carbynoid species provoke C(sp2)-C(sp2) bond scission in alkenes by inserting a monovalent carbon unit between both sp2-hybridized carbons. This skeletal remodeling process accesses synthetically useful allyl cation intermediates that conduct to valuable allylic building blocks upon nucleophile attack. Our results rely on the formation of cyclopropyl-I(III) intermediates able to undergo electrocyclic ring-opening, following the Woodward-Hoffmann-DePuy rules.

Fast screening of aflatoxins in dairy cattle feeds with CE-LIF method combined with preconcentration technique of vortex assisted low density solvent-microextraction.

Aflatoxin contamination in agricultural products poses a great threat to humans and livestock. The aim of this study was to establish a simple, rapid, highly sensitive, and inexpensive method for the simultaneous detection of aflatoxin B1 , B2 , G1 , and G2 in agricultural products. We used a vortex assisted low density solvent-microextraction (VALDS-ME) technique for sample preconcentration and sample detection was achieved with a CE-LIF method. Aflatoxins were separated in an uncoated fused-silica capillary with the MEKC mode and were excited by a 355 nm UV laser to produce native fluorescence for detection. The obtained LOD and LOQ for the four aflatoxins were in the range of 0.002-0.075 and 0.007-0.300 µg/L, respectively, and the analysis time was within 6.5 min. Using the established method, aflatoxins were screened in naturally contaminated dairy cattle feed samples including alfalfa, bran, and corn kernel. The result shows that the alfalfa and bran samples were contaminated with aflatoxins to varying degrees. Compared with other analytical techniques for aflatoxin screening in agricultural products, this CE-LIF method combined with VALDS-ME preconcentration technique is simple, rapid, highly efficient, and inexpensive.

Rumen bacterial diversity of Tibetan sheep (Ovis aries) associated with different forage types on the Qinghai-Tibetan Plateau.

Diet is the great determinant of bacterial composition in the rumen. However, little is known about the rumen bacterial community of Tibetan sheep living in the special ecological environment of the Qinghai-Tibetan Plateau (QTP) of China. In the present study, we used high-throughput sequencing to investigate the rumen bacterial community of Tibetan sheep associated with two primary diets: alpine pasture diet (a continuation of the sheep's natural grazing diet) and oat (Avena sativa) hay diet on the QTP. The results showed that bacterial community richness and species diversity of the oat hay diet group were significantly greater than that of the native pasture diet group (p < 0.05). Principal co-ordinate analysis and analysis of similarities revealed that the bacterial community of the oat hay diet group was distinctly different from that of the native pasture diet group (p < 0.05). Bacteroidetes and Firmicutes were the predominant microbial phyla in the rumen. The rumen of oat-hay-fed sheep had higher proportions of Proteobacteria and novel bacteria species than the rumen of native-pasture-fed sheep. Actinobacteria, an uncommon bacterial phylum, occurred only in the oat-hay-fed group. At the genus level, Komagataeibacter, Ruminococcaceae_UCG-014, and Ruminococcaceae_NK4A214 showed significantly higher relative abundance in the oat-hay-fed sheep than in the native-pasture-fed sheep (p < 0.05). This study is the first of the QTP to employ high-throughput sequencing to examine the influence of diet on the rumen microbiome of Tibetan sheep.

A New Angular Light Scattering Measurement of Particulate Matter Mass Concentration for Homogeneous Spherical Particles.

Under the condition of ultra-low emission for power plants, the particulate matter concentration is significantly lower than that of typical power plants a decade ago, which posed new challenges for the particulate matter monitoring of stationary emission. The monitoring of particulate matter mass concentration based on ensemble light scattering has been found affected by particle size. Thus, this study develops a method of using the scattering angular distribution to obtain the real-time particle size, and then correct the particulate matter concentration with the real-time measured particle size. In this study, a real-time aerosol concentration and particle size measurement setup is constructed with a fixed detector at the forward direction and a rotating detector. The mass concentration is measured by the fixed detector, and the particle size is measured from the intensity ratio of the two detectors. The simulations show that the particle size has power law functionality with the angular spacing of the ripple structure according to Mie theory. Four quartz aerosols with different particle size are tested during the experiment, and the particle size measured from the ripple width is compared with the mass median size measured by an electrical low pressure impactor (ELPI). Both techniques have the same measurement tendency, and the measurement deviation by the ripple width method compared with ELPI is less than 15%. Finally, the measurement error of the real-time mass concentration is reduced from 38% to 18% with correction of the simultaneously measured particle size when particle size has changed.

Versatile Nanostructures from Rice Husk Biomass for Energy Applications.

Converting biomass into valuable products has great benefits in terms of both economic and environmental considerations, and has attracted considerable attention in recent years. Rice husk biomass was initially utilized to produce bulk materials for conventional applications while a variety of advanced nanostructures (NSs) have been fabricated over the past few years. In addition to their low cost and environmental friendliness, RH-derived NSs (RH-NSs) exhibit versatile properties, which are promising for broad applications in various fields. In this Review, we summarize the latest research on RH-NSs, covering their design, fabrication, properties, and applications in the modern energy field. Based on the unique structure and components of RHs, a series of carbon/silicon-based novel NSs with outstanding performances have been exploited, which are difficult to be synthesized using conventional chemical reagents. We also discuss perspective uses of RH-NSs on the basis of the current research progress.

Cadmium stress tolerance in wheat seedlings induced by ascorbic acid was mediated by NO signaling pathways.

Ascorbic acid (AsA) and nitric oxide (NO) are well known and widespread antioxidants and gaseous molecules that regulate plant tolerance to several stresses. However, the relationship between them in plant response to stress, especially heavy stress, is largely unclear. This study demonstrated that both AsA and NO could enhance the tolerance of wheat seedlings to cadmium stress evidenced by root length change, which resulted from their roles in maintaining the balance in reactive oxygen species (ROS) and reducing the absorption of Cd. Furthermore, exogenous AsA led to a significant increase of NO content and endogenous AsA content in wheat roots, which could be weakened by the NO scavenger c-PTIO. In addition, c-PTIO also inhibits the NO-induced production of endogenous AsA. Although the AsA synthesis inhibitor lycorine significantly inhibited the inductive effect of exogenous AsA on endogenous AsA production, it has little effect on NO content. In addition, we found that the protective effects of NO and AsA on Cd stress were removed by c-PTIO and lycorine. These results indicated that NO accumulation could be necessary for exogenous AsA-induced cadmium tolerance and endogenous AsA production, and the exogenous AsA-induced endogenous AsA production was likely mediated by NO signaling pathways and together they induced the tolerance of wheat to cadmium stress.