Ozone Treatment as an Approach to Induce Specialized Compounds in Melissa officinalis Plants.

Plants are constantly subjected to environmental changes that deeply affect their metabolism, leading to the inhibition or synthesis of "specialized" compounds, small organic molecules that play a fundamental role in adaptative responses. In this work, Melissa officinalis L. (an aromatic plant broadly cultivated due to the large amounts of secondary metabolites) plants were exposed to realistic ozone (O3) dosages (80 ppb, 5 h day-1) for 35 consecutive days with the aim to evaluate its potential use as elicitor of specialized metabolite production. Ozone induced stomatal dysfunction throughout the whole experiment, associated with a low photosynthetic performance, a decrease in the potential energy conversion activity of PSII, and an alteration in the total chlorophyll content (-35, -36, -10, and -17% as average compared to the controls, respectively). The production of hydrogen peroxide at 7 days from the beginning of exposure (+47%) resulted in lipid peroxidation and visible injuries. This result suggests metabolic disturbance within the cell and a concomitant alteration in cell homeostasis, probably due to a limited activation of antioxidative mechanisms. Moderate accumulated doses of O3 triggered the accumulation of hydroxycinnamic acids and the up-regulation of the genes encoding enzymes involved in rosmarinic acid, phenylpropanoid, and flavonoid biosynthesis. While high accumulated doses of O3 significantly enhanced the content of hydroxybenzoic acid and flavanone glycosides. Our study shows that the application of O3 at the investigated concentration for a limited period (such as two/three weeks) may become a useful tool to stimulate bioactive compounds production in M. officinalis.

Signalling responses in the bark and foliage of canker-susceptible and -resistant cypress clones inoculated with Seiridium cardinale.

The necrotrophic fungus Seiridium cardinale is the main responsible for Cypress Canker Disease (CCD), a pandemic affecting many Cupressaceae worldwide. The present study aims to elucidate the signalling of the early responses in the bark and foliage of CCD-susceptible and -resistant C. sempervirens clones to S. cardinale inoculation (SI and RI, respectively). In the bark of SI, a peaking production of ethylene (Et) and jasmonic acid (JA) occurred at 3 and 4 days post inoculation (dpi), respectively, suggesting an attempted plant response to the pathogen. A response that, however, was ineffective, as confirmed by the severe accumulation of malondialdehyde by-products at 13 dpi (i.e., lipid peroxidation). Differently, Et emission peaked in RI bark at 3 and 13 dpi, whereas abscisic acid (ABA) accumulated at 1, 4 and 13 dpi, resulting in a lower MDA accumulation (and unchanged levels of antioxidant capacity). In the foliage of SI, Et was produced at 1 and 9 dpi, whereas JA and salicylic acid (SA) accumulated at 1 and 3 dpi. Conversely, an increase of ABA and SA occurred at 1 dpi in the RI foliage. This outcome indicates that some of the observed metabolic alterations, mainly occurring as local defence mechanisms, might be able to gradually shift to a systemic resistance, although an accumulation of MDA was observed in both SI and RI foliage (but with an increased antioxidant capacity reported only in the resistant clone). We believe that the results reported here will be useful for the selection of clones able to limit the spread and damage of CCD.

New perspective for the upscaling of plant functional response to flooding stress in salt marshes using remote sensing.

Understanding the response of salt marshes to flooding is crucial to foresee the fate of these fragile ecosystems, requiring an upscaling approach. In this study we related plant species and community response to multispectral indices aiming at parsing the power of remote sensing to detect the environmental stress due to flooding in lagoon salt marshes. We studied the response of Salicornia fruticosa (L.) L. and associated plant community along a flooding and soil texture gradient in nine lagoon salt marshes in northern Italy. We considered community (i.e., species richness, dry biomass, plant height, dry matter content) and individual traits (i.e., annual growth, pigments, and secondary metabolites) to analyze the effect of flooding depth and its interplay with soil properties. We also carried out a drone multispectral survey, to obtain remote sensing-derived vegetation indices for the upscaling of plant responses to flooding. Plant diversity, biomass and growth all declined as inundation depth increased. The increase of soil clay content exacerbated flooding stress shaping S. fruticosa growth and physiological responses. Multispectral indices were negatively related with flooding depth. We found key species traits rather than other community traits to better explain the variance of multispectral indices. In particular stem length and pigment content (i.e., betacyanin, carotenoids) were more effective than other community traits to predict the spectral indices in an upscaling perspective of salt marsh response to flooding. We proved multispectral indices to potentially capture plant growth and plant eco-physiological responses to flooding at the large scale. These results represent a first fundamental step to establish long term spatial monitoring of marsh acclimation to sea level rise with remote sensing. We further stressed the importance to focus on key species traits as mediators of the entire ecosystem changes, in an ecological upscaling perspective.

Flooding by sea and brackish waters enhances mobility of Cd, Zn and Pb from airborne dusts in coastal soils.

Sea level rise and extreme weather conditions caused by climatic changes enhance the frequency and length of submersion events in coastal soils, causing deposited airborne dusts to get in contact with marine salts. The behaviour of Cd, Zn and Pb from pedogenetic minerals and from dusts from mining and smelting activities, added to two soils under different agricultural management (arable and grassland) was examined after soil flooding for 1, 7 and 30 days with waters of increasing salinities (0, 4.37, 8.75, 17.25 and 34.5 g L-1). A rain water event following 1 d flooding released an extra amount of metals. Concentration of potentially toxic elements (PTE), pH, dissolved inorganic and organic C were measured in solutions collected by gravity from soil columns. Speciation distribution of leached metals and oversaturation parameters were calculated by Visual Minteq 3.0 and showed that complexation by chloride ions for Cd and fulvic acids for Pb were the drivers of solubilisation, while Zn interacted with both. Results showed that marine salts enhance up to 300 times leaching of Cd, and several times that of Zn and Pb from contaminated soils and that airborne toxic elements are much more mobilized than pedogenic ones. Smelter exhaust metals, particularly Pb, were made more mobile than those in mine tailings (up to 55 against 0.7 ng µg-1 Pb). Soil management strongly also influence mobilization by saline water: much lower amounts were leached from the grassland soil. Soil organic matter quality (DOC and humification) affects the extent of mobilization. The length of the flooding period did not result in coherent time trend patterns for the three metals, probably because of the multiple changes in solution parameters, but leached metals were always highly linearly correlated negatively with pH and positively with DOC.

Untangling the role of leaf age specific osmoprotectant and antioxidant responses of two poplar clones under increasing ozone concentrations.

Plants possess different degrees of tolerance to abiotic stress, which can mitigate the detrimental effect of environmental inputs affecting carbon balance. Less is known about the functions of osmoprotectants in scavenging of reactive oxygen species (ROS), generated at different sites depending on leaf age. This study aimed to clarify the osmotic adjustments adopted by old and young leaves of Oxford and I-214 poplar clones [differing in ozone (O3) sensitivity] to cope with three levels of O3 [ambient (AA), and two elevated O3 levels]. In both clones, the impact of intermediate O3 concentrations (1.5 × AA) on ROS production appeared to be leaf age-specific, given the accumulation of hydrogen peroxide (H2O2) observed only in old leaves of the Oxford plants and in young leaves of the I-214 ones (2- fold higher than AA and +79%, respectively). The induction of an oxidative burst was associated with membrane injury, indicating an inadequate response of the antioxidative systems [decrease of lutein and ß-carotene (-37 and -85% in the old leaves of the Oxford plants), accumulation of proline and tocopherols (+60 and +12% in the young leaves of the I-214 ones)]. Intermediate O3 concentrations reacted with unsaturated lipids of the plasma membrane in old and young leaves of the Oxford plants, leading to an increase of malondialdehyde by-products (more than 2- fold higher than AA), while no effect was recorded for I-214. The impact of the highest O3 concentrations (2.0 × AA) on ROS production did not appear clone-specific, which may react with cell wall components by leading to oxidative pressure. Outcomes demonstrated the ability of young leaves of I-214 plants in contain O3 phytotoxic effects.

Potential of herbaceous plant species for copper (Cu) accumulation.

The removal of copper (Cu) in soils by green technology is less treated with urgency, as it is a plant micronutrient. We examined the efficiency of Cu shoot accumulation by herbaceous plants in Cu-contaminated and non-contaminated soils in Trhové Dusniky and Podles, respectively, in the Czech Republic. The total soil Cu content of 81 mg kg-1 in Trhové Dusniky indicated a slight contamination level compared to 50 mg kg-1, the permissible value by WHO, and < 35 in Podlesí, representing a clean environment. The Cu content was above the permissible value in plants (10 mg kg-1 by WHO) in herbaceous speciesat the control site without trees: Stachys palustris L. (10.8 mg kg-1), Cirsium arvense L. (11.3 mg kg-1), Achillea millefolium L. (12.1 mg kg-1), Anthemis arvense L. (13.2 mg kg-1), and Calamagrostis epigejos L. (13.7 mg kg-1). In addition, Hypericum maculatum Crantz (10.6 mg kg-1), Campanula patula L. (11.3 mg kg-1), C. arvense (15 mg kg-1), and the highest accumulation in shoot of Equisetum arvense L. (37.1 mg kg-1), all under the canopy of trees at the uncontaminated site, were above the WHO value. Leucanthemum Vulgare (Lam.) and Plantago lanceolata L. recorded 11.2 mg kg-1 and 11.5 mg kg-1, respectively, in the soil of the Cu-contaminated site. These herbaceous species can support the phyto-management of Cu-contaminated soils, especially E. arvense. Critical attention is well-required in the medicinal application of herbaceous plants in treating human ailments due to their Cu accumulation potentials above the threshold. Spontaneous surveys and analysis of Cu speciation in herbaceous species can reveal suitable plants to decontaminate soils and provide caution on consumable products, especially bioactive compounds.

Exogenous application of melatonin protects bean and tobacco plants against ozone damage by improving antioxidant enzyme activities, enhancing photosynthetic performance, and preventing membrane damage.

Ozone (O3) pollution is harmful to plants and ecosystems. Several chemicals have been evaluated to protect plants against O3 deleterious effects. However, they are not adequately efficient and/or the environmental safety of their application is questioned. Hence, new chemicals that provide sufficient protection while being safer for environmental application are needed. This study investigates the response of two O3-sensitive plant species (Phaseolus vulgaris L. cv. Pinto and Nicotiana tabacum L. cv. Bel-W3) leaf-sprayed with deionized water (W, control), ethylenediurea (EDU, 1 mM) or melatonin at lower (1 mM) or higher (3 mM) concentrations (Mel_L and Mel_H, respectively), and then exposed to a square wave of 200 ppb O3, lasting 1 day (5 h day-1) for bean and 2 days (8 h day-1) for tobacco. In both species, the photosynthetic activity of O3-exposed plants was about halved. O3-induced membrane damage was also confirmed by increased malondialdehyde (MDA) byproducts compared to control (W). In EDU- and Mel-treated bean plants, the photosynthetic performance was not influenced by O3, leading to reduction of the incidence and severity of O3 visible injury. In bean plants, Mel_L mitigated the detrimental effect of O3 by boosting antioxidant enzyme activities or osmoprotectants (e.g. abscisic acid, proline, and glutathione transferase). In Mel_L-sprayed tobacco plants, O3 negatively influenced the photosynthetic activity. Conversely, Mel_H ameliorated the O3-induced oxidative stress by preserving the photosynthetic performance, preventing membrane damage, and reducing the visible injuries extent. Although EDU performed better, melatonin protected plants against O3 phytotoxicity, suggesting its potential application as a bio-safer and eco-friendlier phytoprotectant against O3. It is worth noting that the content of melatonin in EDU-treated plants remained unchanged, indicating that the protectant mode of action of EDU is not Mel-related.

Restricted O2 consumption in pea roots induced by hexanoic acid is linked to depletion of Krebs cycle substrates.

Plant roots are exposed to hypoxia in waterlogged soils, and they are further challenged by specific phytotoxins produced by microorganisms in such conditions. One such toxin is hexanoic acid (HxA), which, at toxic levels, causes a strong decline in root O2 consumption. However, the mechanism underlying this process is still unknown. We treated pea (Pisum sativum L.) roots with 20 mM HxA at pH 5.0 and 6.0 for a short time (1 h) and measured leakage of key electrolytes such as metal cations, malate, citrate and nonstructural carbohydrates (NSC). After treatment, mitochondria were isolated to assess their functionality evaluated as electrical potential and O2 consumption rate. HxA treatment resulted in root tissue extrusion of K+ , malate, citrate and NSC, but only the leakage of the organic acids and NSC increased at pH 5.0, concomitantly with the inhibition of O2 consumption. The activity of mitochondria isolated from treated roots was almost unaffected, showing just a slight decrease in oxygen consumption after treatment at pH 5.0. Similar results were obtained by treating the pea roots with another organic acid with a short carbon chain, that is, butyric acid. Based on these results, we propose a model in which HxA, in its undissociated form prevalent at acidic pH, stimulates the efflux of citrate, malate and NSC, which would, in turn, cause starvation of mitochondrial respiratory substrates of the Krebs cycle and a consequent decline in O2 consumption. Cation extrusion would be a compensatory mechanism in order to restore plasma membrane potential.

Epidemiology of perinatal depression in Italy: systematic review and meta-analysis.

INTRODUCTION: This review aims to synthesise the studies that have estimated the prevalence of perinatal depression in Italy, summarising the results of the existing literature based on their quality. MATERIALS AND METHODS: Systematic searches were conducted in four major databases, and a random effect meta-analysis was performed to achieve the pooled variance of perinatal depression. RESULTS: The pooled prepartum risk of depression prevalence was 20.2% (CI 95% 15.3-24.5) while the postpartum risk of depression prevalence was 27.5% (CI 95% 17.8-37.3) for an Edinburgh Postnatal Depression Scale (EPDS) cut-off score ≥9 and 11.1% (CI 95% 6.0-16.2) for an EPDS cut-off score ≥12. Significant publication bias was found and was determined by the presence of a small study with a low prevalence and a large study with a high prevalence. CONCLUSION: The prevalence of perinatal risk of depression is similar to that reported in other countries. The high prevalence of prepartum risk suggests the need to activate specific prevention actions during this period.

A meta-analysis of plant tissue O2 dynamics.

Adequate tissue O2 supply is crucial for plant function. We aimed to identify the environmental conditions and plant characteristics that affect plant tissue O2 status. We extracted data and performed meta-analysis on >1500 published tissue O2 measurements from 112 species. Tissue O2 status ranged from anoxic conditions in roots to >53kPa in submerged, photosynthesising shoots. Using information-theoretic model selection, we identified 'submergence', 'light', 'tissue type' as well as 'light×submergence' interaction as significant drivers of tissue O2 status. Median O2 status were especially low (Solanum tuberosum ) tubers and root nodules. Mean shoot and root O2 were ~25% higher in light than in dark when shoots had atmospheric contact. However, light showed a significant interaction with submergence on plant O2 , with a submergence-induced 44% increase in light, compared with a 42% decline in dark, relative to plants with atmospheric contact. During submergence, ambient water column O2 and shoot tissue O2 correlated stronger in darkness than in light conditions. Although use of miniaturised Clark-type O2 electrodes has enhanced understanding of plant O2 dynamics, application of non-invasive methods in plants is still lacking behind its widespread use in mammalian tissues.

Functional responses of two Mediterranean pine species in an ozone Free-Air Controlled Exposure (FACE) experiment.

Effects of the phytotoxic and widespread ozone (O3) pollution may be species specific, but knowledge on Mediterranean conifer responses to long-term realistic exposure is still limited. We examined responses regarding to photosynthesis, needle biochemical stress markers and carbon and nitrogen (N) isotopes of two Mediterranean pine species (Pinus halepensis Mill. and Pinus pinea L.). Seedlings were grown in a Free-Air Controlled Exposure experiment with three levels of O3 (ambient air, AA [38.7 p.p.b. as daily average]; 1.5 × AA and 2.0 × AA) during the growing season (May-October 2019). In P. halepensis, O3 caused a significant decrease in the photosynthetic rate, which was mainly due to a reduction of both stomatal and mesophyll diffusion conductance to CO2. Isotopic analyses indicated a cumulative or memory effect of O3 exposure on this species, as the negative effects were highlighted only in the late growing season in association with a reduced biochemical defense capacity. On the other hand, there was no clear effect of O3 on photosynthesis in P. pinea. However, this species showed enhanced N allocation to leaves to compensate for reduced photosynthetic N- use efficiency. We conclude that functional responses to O3 are different between the two species determining that P. halepensis with thin needles was relatively sensitive to O3, while P. pinea with thicker needles was more resistant due to a potentially low O3 load per unit mass of mesophyll cells, which may affect species-specific resilience in O3-polluted Mediterranean pine forests.

Evaluation of Fruquintinib in the Continuum of Care of Patients with Colorectal Cancer.

The management of patients with metastatic colorectal cancer (mCRC) has the continuum of care as the treatment paradigm. To date, trifluridine/tipiracil, a biochemically modulated fluoropyrimidine, and regorafenib, a multi-kinase inhibitor, remain the main options for the majority of patients who progressed to standard doublet- or triplet-based chemotherapies, although a tailored approach could be indicated in certain circumstances. Being highly selective for vascular endothelial growth factor receptor (VEGFR)-1, -2 and -3, fruquintinib demonstrated a strong anti-tumor activity in preclinical models and received approval from China's National Medical Products Administration (NMPA) in 2018 for the treatment of patients with chemo-refractory mCRC. The approval was based on the results of the phase III FRESCO trial. Then, in order to overcome geographic differences in clinical practice, the FRESCO-2 trial was conducted in the US, Europe, Japan, and Australia. In a heavily pretreated patient population, the study met its primary endpoint, demonstrating an advantage of fruquintinib over a placebo in overall survival (OS). Here, we review the clinical development of fruquintinib and its perspectives in gastrointestinal cancers. Then, we discuss the introduction of fruquintinib in the continuum of care of CRC paying special attention to unmet needs, including the identification of cross-resistant and potentially susceptible populations, evaluation of radiological response, and identification of novel biomarkers of clinical benefit.

Ozone-Induced Biochemical and Molecular Changes in Vitis vinifera Leaves and Responses to Botrytis cinerea Infections.

To investigate how plants cope with multi-stress conditions, we analyzed the biochemical and molecular changes of Vitis vinifera leaves subjected to single or sequential double stresses (infection by Botrytis cinerea (Bc) and ozone (O3, 100 ppb for 3 h) treatment). In Bc+/O3- leaves, the hydrogen peroxide (H2O2) induction (observed at 12 and 24 h from the end of treatment (FET)) triggered a production of ethylene (Et; +35% compared with Bc-/O3- leaves), which was preceded by an increase of salicylic acid (SA; +45%). This result confirms a crosstalk between SA- and Et-related signaling pathways in lesion spread. The ozone induced an early synthesis of Et followed by jasmonic acid (JA) and SA production (about 2-fold higher), where Et and SA signaling triggered reactive oxygen species production by establishing a feedback loop, and JA attenuated this cycle by reducing Et biosynthesis. In Bc+ + O3+ leaves, Et peaked at 6 and 12 h FET, before SA confirmed a crosstalk between Et- and SA-related signaling pathways in lesion propagation. In O3+ + Bc+ leaves, the H2O2 induction triggered an accumulation of JA and Et, demonstrating a synergistic action in the regulation of defence reactions. The divergence in these profiles suggests a rather complex network of events in the transcriptional regulation of genes involved in the systemic acquired resistance.

Responses of key root traits in the genus Oryza to soil flooding mimicked by stagnant, deoxygenated nutrient solution.

Excess water can induce flooding stress resulting in yield loss, even in wetland crops such as rice (Oryza). However, traits from species of wild Oryza have already been used to improve tolerance to abiotic stress in cultivated rice. This study aimed to establish root responses to sudden soil flooding among eight wild relatives of rice with different habitat preferences benchmarked against three genotypes of O. sativa. Plants were raised hydroponically, mimicking drained or flooded soils, to assess the plasticity of adventitious roots. Traits included were apparent permeance (PA) to O2 of the outer part of the roots, radial water loss, tissue porosity, apoplastic barriers in the exodermis, and root anatomical traits. These were analysed using a plasticity index and hierarchical clustering based on principal component analysis. For example, O. brachyantha, a wetland species, possessed very low tissue porosity compared with other wetland species, whereas dryland species O. latifolia and O. granulata exhibited significantly lower plasticity compared with wetland species and clustered in their own group. Most species clustered according to growing conditions based on PA, radial water loss, root porosity, and key anatomical traits, indicating strong anatomical and physiological responses to sudden soil flooding.

Sustainable Strategies to Counteract Mycotoxins Contamination and Cowpea Weevil in Chickpea Seeds during Post-Harvest.

Mycotoxins contamination and pest infestation of foods and feeds represent a pivotal threat for food safety and security worldwide, with crucial implications for human and animal health. Controlled atmosphere could be a sustainable strategy to reduce mycotoxins content and counteract the vitality of deleterious organisms in foodstuff. Ozone treatment (O3, 500 ppb for 30, 60 or 90 min) and high nitrogen concentration (N2, 99% for 21 consecutive days) were tested in the post-harvest management of four batches of Cicer arietinum grains to control the presence of mycotoxigenic fungi and their secondary metabolites, as well as pest (i.e., Callosobruchus maculatus) infestation. At the end of the treatment, O3 significantly decreased the incidence of Penicillium spp. (by an average of -50%, independently to the time of exposure) and reduced the patulin and aflatoxins content after 30 min (-85 and -100%, respectively). High N2 concentrations remarkably reduced mycotoxins contamination (by an average of -94%) and induced pest mortality (at 100% after 5 days of exposure). These results confirm the promising potential of O3 and N2 in post-harvest conservation strategies, leading to further investigations to evaluate the effects on the qualitative characteristics of grains.

Mutations matter: An observational study of the prognostic and predictive value of KRAS mutations in metastatic colorectal cancer.

Background: About half of metastatic colorectal cancers (CRCs) harbor Rat Sarcoma (RAS) activating mutations as oncogenic driver, but the prognostic role of RAS mutations is not fully elucidated. Interestingly, specific hotspot mutations have been identified as potential candidates for novel targeted therapies in several malignancies as per G12C. This study aims at evaluating the association between KRAS hotspot mutations and patient characteristics, prognosis and response to antiangiogenic drugs. Methods: Data from RAS-mutated CRC patients referred to Careggi University Hospital, between January 2017 and April 2022 were retrospectively and prospectively collected. Tumor samples were assessed for RAS mutation status using MALDI-TOF Mass Spectrometry, Myriapod NGS-56G Onco Panel, or Myriapod NGS Cancer Panel DNA. Results: Among 1047 patients with available RAS mutational status, 183 KRAS-mutated patients with advanced CRC had adequate data for clinicopathological and survival analysis. KRAS mutations occurred at codon 12 in 67.2% of cases, codon 13 in 23.5%, codon 61 in 2.2%, and other codons in 8.2%. G12C mutation was identified in 7.1% of patients and exon 4 mutations in 7.1%. KRAS G12D mutation, as compared to other mutations, was significantly associated with liver metastases (1-sided p=0.005) and male sex (1-sided p=0.039), KRAS G12C mutation with peritoneal metastases (1-sided p=0.035), KRAS G12V mutation with female sex (1-sided p=0.025) and no surgery for primary tumor (1-sided p=0.005). No associations were observed between specific KRAS variants and age, ECOG PS, site of primary tumor, pattern of recurrence for resected patients, and lung, distant lymph node, bone, or brain metastases.Overall survival (OS) was significantly longer in patients with KRAS exon 4 mutations than in those with other KRAS mutations (mOS 43.6 months vs 20.6 months; HR 0.45 [0.21-0.99], p=0.04). No difference in survival was observed for mutations at codon 12/13/61 (p=0.1). Treatment with bevacizumab (BV) increased significatively mPFS (p=0.036) and mOS (p=0.019) of the entire population with a substantial benefit in mOS for G12V mutation (p=0.031). Conclusions: Patterns of presentation and prognosis among patients with specific RAS hotspot mutations deserve to be extensively studied in large datasets, with a specific attention to the uncommon isoforms and the role of anti-angiogenic drugs.

Flooding and Soil Properties Control Plant Intra- and Interspecific Interactions in Salt Marshes.

The stress gradient hypothesis (SGH) states that plant-plant interactions shift from competition to facilitation in increasing stress conditions. In salt marshes, edaphic properties can weaken the application of the SGH by amplifying the intensity of flooding and controlling plant zonation. We identified facilitative and competitive interactions along flooding gradients and tested the role of edaphic properties in exacerbating stress and shaping plant-plant interactions. Morphological traits of two target halophytes (Limonium narbonense and Sarcocornia fruticosa), flooding intensity, soil texture and soil organic C were recorded. The relative plant fitness index was assessed for the two species based on the relative growth in plurispecific rather than monospecific plant communities. Plant fitness increased with increasing stress supporting the SGH. L. narbonense showed larger fitness in plurispecific stands whereas S. fruticosa performed better in conspecific stands. Significant intra- or interspecific interactions were observed along the stress gradient defined by the combination of flooding and clay content in soil. When considering the limited soil organic C as stressor, soil properties were more important than flooding in defining plant-plant interactions. We highlight the need for future improvements of the SGH approach by including edaphic stressors in the model and their possible interactions with the main abiotic drivers of zonation.

The Oneiric Activity during and after the COVID-19 Total Lockdown in Italy: A Longitudinal Study.

A growing body of evidence highlights that the COVID-19 pandemic affected oneiric activity. However, only a few studies have assessed the longitudinal changes in dream phenomenology during different phases of the pandemic, often focused on a limited number of dream variables. The aim of the present study was to provide an exhaustive assessment of dream features during total lockdown (TL) and a post-lockdown (PL) period characterized by eased restrictive measures in Italy. We performed a longitudinal study using a web-based survey to collect demographic, COVID-19 related, clinical, sleep, and dream data at TL and PL. Our final sample included 108 participants. The high frequency of poor sleep quality, anxiety, and depressive symptoms observed during TL remained stable at PL, while sleep latency (t = −4.09; p < 0.001) and PTSD-related disruptive nocturnal behaviors (t = −5.68; p < 0.001) exhibited a reduction at PL. A PL decrease in time spent with digital media was observed (t = −2.77; p = 0.007). We found a strong PL reduction in dream frequency (t = −5.49; p < 0.001), emotional load (t = −2.71; p = 0.008), vividness (t = −4.90; p < 0.001), bizarreness (t = −4.05; p < 0.001), length (t = −4.67; p < 0.001), and lucid dream frequency (t = −2.40; p = 0.018). Fear was the most frequently reported emotion in dreams at TL (26.9%) and PL (22.2%). Only the frequency of specific lockdown-related dream contents exhibited a reduction at PL. These findings highlight that the end of the home confinement had a strong impact on the oneiric activity, in the direction of reduced dream frequency, intensity, and lockdown-related contents. The co-occurrence of such changes with a decline in nocturnal PTSD-related symptoms, sleep latency, and time with digital media suggests an influence of post-traumatic stress levels, lifestyle modifications, and sleep pattern on dream changes during different phases of the pandemic. The stable prevalence of fear in dreams and the large frequency of poor sleep quality, depressive symptoms, and anxiety are probably related to the persistence of many negative consequences of the pandemic. Overall, these results are consistent with the continuity hypothesis of dreams.

Antioxidants and Phytohormones Act in Coordination to Regulate Sage Response to Long Term Ozone Exposure.

Antioxidants and phytohormones are hallmarks of abiotic stress responses in plants. Although it is known that they can offer cell protection or accelerate programmed cell death (PCD) depending on the level of stress, the involvement of these metabolites in stress acclimation is still not fully elucidated. Here, we showed the role of antioxidants and phytohormones in Salvia officinalis tolerance to long-term ozone (O3) exposure (120 ppb for 36 days, 5 h day-1). Salicylic acid (SA) content was increased under O3 throughout the whole experiment (+150%, as average compared with control), being required to maintain the cellular redox state and potentiate defense responses. This accumulation was induced before the production of ethylene (ET), suggesting that ET was controlled by SA during O3 exposure to modulate the magnitude of chlorosis formation and the cell redox balance (by regulating ascorbate and glutathione levels). The synthesis and/or regeneration of these antioxidants did not protect membranes from lipid peroxidation, as demonstrated by the accumulation of malondialdehyde (+23% as average). However, these processes of lipid oxidation did not include the synthesis of the membrane breakdown products, as confirmed by the unchanged values of jasmonic acid, thus indicating that this compound was not involved in the regulation of PCD strategies.

Ivosidenib in IDH1-mutated cholangiocarcinoma: Clinical evaluation and future directions.

To date, treatment options for patients with chemorefractory cholangiocarcinoma (CCA) are limited. However, the advancements in molecular techniques have recently increased the opportunity to offer molecularly targeted therapies to patients with several cancer types and some targetable oncogenic alterations have been identified also in CCA. Among these potentially actionable molecular alterations, isocitrate dehydrogenase-1 (IDH1) mutations have been detected in approximately 10-20% of intrahepatic CCA (iCCA). IDH1 is responsible for the accumulation of oncometabolites inducing epigenetic changes that are involved in various signaling pathways. Ivosidenib is the first IDH1 inhibitor which significantly improved progression-free survival (PFS) (2.7 vs 1.4 months) and overall survival (OS) (10.3 vs 5.1 months [adjusted median OS]) compared with placebo in chemorefractory IDH1-mutated CCA. The very low incidence of grade (G) 3-4 adverse events (AEs) and treatment discontinuation due to toxicity, associated with a significantly less marked decline in health-related quality of life for patients in the ivosidenib group than in placebo group, facilitates patient adherence and clinician confidence. Here, we review the development of ivosidenib in CCA patients and evaluate the clinical impact of the results of the phase III ClarIDHy trial which was responsible for the Food and Drug Administration (FDA) approval for patients with IDH1-mutated CCA whose disease progressed after standard chemotherapy (CT). We also discuss the known primary and secondary resistance mechanisms, including concomitant and acquired mutations in other genes (e.g. IDH2 mutations), second-site mutation in IDH1, and enhanced activation of other pathways (e.g. PI3K/AKT/mTOR pathway). Finally we examine the future directions, as the opportunity to combine ivosidenib with other synergistic agents, including standard chemotherapy (CT), immune checkpoint inhibitors (ICIs), and IDH2 inhibitors.