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Ozone (O 3 ) pollution is a persistent environmental issue worldwide, which causes widespread damage to vegetation, deteriorating plant health and reducing plant productivity. Ethylenediurea (EDU) is a synthetic chemical that has been widely applied in scientific studies as a protectant against O 3 phytotoxicities. Despite four decades of active research, the exact mechanisms to explain its mode of action remain unclear. Here, we aimed to reveal whether EDU's phytoprotective property is due to its control over stomatal regulation and/or its action as a nitrogen (N) fertilizer, utilizing stomatal-unresponsive plants of a hybrid poplar (Populus koreana × trichocarpa cv. Peace) grown in a free-air O 3 -concenctration enrichment (FACE) facility. Plants were treated with water (WAT), EDU (400 mg L -1 ), or EDU's constitutive amount of N every nine days, and exposed to ambient (AOZ) or elevated (EOZ) O 3 during a growing season (June-September). EOZ led to extensive foliar injuries (but protected against rust disease), lower photosynthetic rate (A), impaired dynamics of responses of A to changes in light intensity, and smaller total plant leaf area. EDU protected against common phytotoxicities caused by EOZ without inducing stomatal closure, since stomatal conductance (g s ) was generally unresponsive to the experimental treatments. EDU also modulated the dynamic response of A to light fluctuations under O 3 stress. N addition acted as a fertilizer but did not satisfactorily protect plants against O 3 phytotoxicities. The results suggest that EDU protects against O 3 phytotoxicity not by adding N or controlling stomata, which provides a new insight into our understanding of the mode of action of EDU as a protectant against O 3 phytotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Evaluations of ozone effects on vegetation across the globe over the last seven decades have mostly incorporated exposure levels that were multi-fold the preindustrial concentrations. As such, global risk assessments and derivation of critical levels for protecting plants and food supplies were based on extrapolation from high to low exposure levels. These were developed in an era when it was thought that stress biology is framed around a linear dose-response. However, it has recently emerged that stress biology commonly displays non-linear, hormetic processes. The current biological understanding highlights that the strategy of extrapolating from high to low exposure levels may lead to biased estimates. Here, we analyzed a diverse sample of published empirical data of approximately 500 stimulatory, hormetic-like dose-responses induced by ozone in plants. The median value of the maximum stimulatory responses induced by elevated ozone was 124%, and commonly <150%, of the background response (control), independently of species and response variable. The maximum stimulatory response to ozone was similar among types of response variables and major plant species. It was also similar among clades, between herbaceous and woody plants, between deciduous and evergreen trees, and between annual and perennial herbaceous plants. There were modest differences in the stimulatory response between genera and between families which may reflect different experimental designs and conditions among studies. The responses varied significantly upon type of exposure system, with open-top chambers (OTCs) underestimating the maximum stimulatory response compared to free-air ozone-concentration enrichment (FACE) systems. These findings suggest that plants show a generalized hormetic stimulation by ozone which is constrained within certain limits of biological plasticity, being highly generalizable, evolutionarily based, and maintained over ecological scales. They further highlight that non-linear responses should be taken into account when assessing the ozone effects on plants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ammonium sulfate [(NH 4 ) 2 SO 4 ] deposition and elevated ozone (O 3 ) concentrations may negatively affect plants and trophic interactions. This study aimed to evaluate for the first time the interactive effects of high (NH 4 ) 2 SO 4 load and elevated O 3 levels on cauliflower (Brassica oleracea L.) under field conditions. Cauliflower seedlings were treated with 0 (AS0) or 50 (AS50) kg ha -1 (NH 4 ) 2 SO 4 and exposed to ambient (AOZ, ≈20 ppb) or elevated (EOZ, ≈55 ppb) O 3 for about one month, in a Free Air O 3 Concentration Enrichment (FACE) system. The oligophagous diamondback moth (Plutella xylostella Linnaeus, 1758) showed a clear preference towards the seedlings treated with AS50, which intensively grazed. Plant-herbivore interactions were driven by (NH 4 ) 2 SO 4 availability, rather than O 3 , via increased nitrogen content in the leaves. Further laboratory bioassays were followed to confirm the validity of these observations using polyphagous Eri silkmoth larvae (Samia ricini) as a biological model in a standardized experimental setup. Choice assays, where larvae could select leaves among leaf samples from the different experimental conditions, and no-choice assays, where larvae could graze leaves from just one experimental condition, were conducted. In the choice assay, the larvae preferred AS50-treated leaves, in agreement with the field observations with diamondback moth. In the no-choice assay, larval body mass growth was inhibited when fed with leaves treated with EOZ and/or AS50. Larvae fed with AS50-treated leaves displayed increased mortality. These observations coincide with higher NO 3 and Zn content in AS50-treated leaves. This study shows that plant-herbivore interactions can be driven by (NH 4 ) 2 SO 4 availability, independently of O 3 , and suggests that high N deposition may have severe health implications in animals consuming such plant tissues. Key message: Plant-herbivore interactions are driven by high (NH 4 ) 2 SO 4 availability, independently of O 3 ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The nature of the dose-response relationship in the low dose zone and how this concept may be used by regulatory agencies for science-based policy guidance and risk assessment practices are addressed here by using the effects of surface ozone (O 3 ) on plants as a key example for dynamic ecosystems sustainability. This paper evaluates the current use of the linear non-threshold (LNT) dose-response model for O 3 . The LNT model has been typically applied in limited field studies which measured damage from high exposures, and used to estimate responses to lower concentrations. This risk assessment strategy ignores the possibility of biological acclimation to low doses of stressor agents. The upregulation of adaptive responses by low O 3 concentrations typically yields pleiotropic responses, with some induced endpoints displaying hormetic-like biphasic dose-response relationships. Such observations recognize the need for risk assessment flexibility depending upon the endpoints measured, background responses, as well as possible dose-time compensatory responses. Regulatory modeling strategies would be significantly improved by the adoption of the hormetic dose response as a formal/routine risk assessment option based on its substantial support within the literature, capacity to describe the entire dose-response continuum, documented explanatory dose-dependent mechanisms, and flexibility to default to a threshold feature when background responses preclude application of biphasic dose responses., Capsule: The processes of ozone hazard and risk assessment can be enhanced by incorporating hormesis into their principles and practices., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Melatonin is a hormone produced in animals by the pineal gland and in plants under stress. Melatonin research has expanded rapidly, affecting an impressive enhancement in the understanding of its functions in plants and animals. However, far less focus has been directed to clarifying the nature of melatonin dose-response relationships. Here, we provide substantial evidence of melatonin-induced biphasic dose-response relationships from a series of independent studies involving plant and animal models. The characteristics of these dose responses are similar to those of the broad toxicological and pharmacological hormesis literature. Our analysis suggests that melatonin, in coordination with the circadian rhythms, is involved in stress adaptive responses, and may act as a conditioning agent protecting organisms against subsequent health threats within an hormetic framework. Incorporation of melatonin-induced hormesis in research protocols has the potential to enhance the treatment of neuropsychiatric diseases, cancers, and other animal diseases, as well as protection against environmental stress and to increase plant productivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It has long been debated whether a little stress may be "good" for you. Extensive evidence has now sufficiently accumulated demonstrating that low doses of a vast range of chemical and physical agents induce protective/beneficial effects while the opposite occurs at higher doses, a phenomenon known as hormesis. Low doses of environmental agents have recently induced autophagy, a critical adaptive response that protects essentially all cell types, as well as being transgenerational via epigenetic mechanisms. These collective findings highlight a generalized and substantial ongoing dose-response transformation with significant implications for disease biology and clinical applications, challenging the history and practice of toxicology and pharmacology along with an appeal to stake holders to reexamine the process of risk assessment, with the goal of optimizing public health rather than simply avoiding harm., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Ground-level ozone (O 3 ) levels are nowadays elevated in wide regions of the Earth, causing significant effects on plants that finally lead to suppressed productivity and yield losses. Ethylenediurea (EDU) is a chemical compound which is widely used in research projects as phytoprotectant against O 3 injury. The EDU mode of action remains still unclear, while there are indications that EDU may contribute to plants with nitrogen (N) when the soil is poor in N and the plants have relatively small leaf area. To reveal whether the N content of EDU acts as a fertilizer to plants when the soil is not poor in N and the plants have relatively large total plant leaf area, willow plants (Salix sachalinensis Fr. Schm) were exposed to low ambient O 3 levels and treated ten times (9-day interval) with 200mL soil drench containing 0, 800 or 1600mg EDU L -1 . Fertilizer was added to a nutrient-poor soil, and the plants had an average plant leaf area of 9.1m 2 at the beginning of EDU treatments. Indications for EDU-induced hormesis in maximum electron transport rate (J max ) and ratio of intercellular to ambient CO 2 concentration (C i :C a ) were observed at the end of the experiment. No other EDU-induced effects on leaf greenness and N content, maximum quantum yield of photosystem II (F v /F m ), gas exchange, growth and matter production suggest that EDU did not act as N fertilizer and did not cause toxicity under these experimental conditions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Casitas B-lineage lymphoma b (Cblb) is a negative regulator of T-cell activation and dysfunction of Cblb in rats and mice results in autoimmunity. In particular, a nonsense mutation in Cblb has been identified in a rat model of autoimmune type 1 diabetes. To clarify the possible involvement of CBLB mutation in type 1 diabetes in humans, we performed mutation screening of CBLB and characterized functional properties of the mutations in Japanese subjects. Six missense mutations (A155V, F328L, N466D, K837R, T882A, and R968L) were identified in one diabetic subject each, excepting N466D. Of these mutations, F328L showed impaired suppression of T-cell activation and was a loss-of-function mutation. These data suggest that the F328L mutation is involved in the development of autoimmune diseases including type 1 diabetes, and also provide insight into the structure-function relationship of CBLB protein.

We present a case of malignant vaginal melanoma studied by magnetic resonance imaging (MRI). A dark irregular mass was noted in the anterior wall of the vaginal cavity on physical examination. On fat-saturated T1-weighted MRI, the vaginal lesion was demonstrated more clearly than by conventional T1- and T2-weighted images. Furthermore, the fat-saturated image detected the bladder metastasis from the vaginal lesion.

Objective: Our purpose was to describe embryonal anatomic structures by use of intrauterine ultrasonography with a 20 MHz flexible catheter-based, high-resolution, real-time miniature transducer., Study Design: Thirty-four women about to undergo therapeutic abortion from 7 to 9.9 weeks' gestation were studied with specially developed catheter-based, high-resolution, real-time miniature (2.4 mm outer diameter) ultrasonography transducer (20 MHz). A percentage of anatomic structures visualized at each gestational age is presented., Results: The number and the clarity of structures increased from 7 to 8 weeks of gestation; however, the image quality was degraded because of the increasing fetal size at 9 weeks. At 8 weeks secondary brain vesicles, spine, midgut herniation, liver, upper and lower limb buds, and sacral tail were visualized in all fetuses. The four-chamber view was first identified at 8 weeks, as were fingers or toes. The stomach was first noted at 9 weeks. The umbilical cord cyst was visualized in 8% of embryos at 7 weeks' gestation and in 29% of embryos at 8 weeks. One cystic hygroma was diagnosed at 8 weeks 5 days., Conclusion: Intrauterine ultrasonography provides information on the visualization of anatomic structures of the embryo. In this limited series one embryonic malformation was demonstrated, and thus there is a potential for its use in the detection of malformations. These results suggest that intrauterine ultrasonography has the potential to be a supplement to transvaginal ultrasonography during the first trimester in high-risk pregnancies.

Objective: Our purpose was to evaluate whether intratumoral blood flow velocity measured by transvaginal Doppler ultrasonography would afford better discrimination between benign and malignant adnexal tumors., Study Design: One hundred two patients with adnexal tumors (72 benign, 30 malignant) were studied with transvaginal B-mode, color, and pulsed Doppler ultrasonography before surgery., Results: Sixty-five benign tumors (90.3%) had abnormal morphologic features suggesting malignancy, and blood flow was detected in 29 (40.3%). The peak systolic velocity was 13.1 +/- 9.1 cm/sec and the resistance index was 0.563 +/- 0.177. All malignant tumors had abnormal morphologic features and blood flow was detectable in all cases. The peak systolic velocity was 23.9 +/- 11.5 cm/sec and the resistance index was 0.488 +/- 0.118. When 16 cm/sec was considered as the cutoff value of peak systolic velocity, the sensitivity and specificity of peak systolic velocity in detecting malignant adnexal tumors were 83.3% and 91.6%, respectively. The sensitivity and specificity of the resistance index (cutoff value 0.72) was 93.3% and 68.1%, respectively. There was no significant difference in sensitivity between peak systolic velocity and resistance index. The specificity of the peak systolic velocity was significantly higher than that of the resistance index (p < 0.05). Moreover, the sensitivity of the peak systolic velocity did not significantly differ from that with transvaginal ultrasonography diagnosis (86.7%), and the specificity of the peak systolic velocity was significantly higher than that of transvaginal ultrasonography (69.4%)., Conclusion: These results suggest that peak systolic velocity obtained from intratumoral abnormal morphologic features provides a superior means for differentiating malignant from benign adnexal tumors.

We describe a case of vasa previa diagnosed antenatally with transvaginal color Doppler ultrasonography. The diagnosis was confirmed at cesarean delivery. The benefits and advantages of the use of transvaginal color Doppler ultrasonography to diagnose vasa previa in utero are discussed.

A case of intrauterine fetal death at 14 week's gestation in a mother with systemic lupus erythematosus is described. Doppler ultrasonography performed within 24 hours before fetal death showed reverse end-diastolic flow velocities on umbilical artery velocity waveforms. The placental alteration causing this early gestation is discussed.

We present herein a case of valvar aortic stenosis diagnosed antenatally, using color and pulsed Doppler echocardiography and magnetic resonance imaging. The benefit and advantages of the use of magnetic resonance imaging, complementary to the Doppler echocardiography, are discussed.

Seventy-two continuous-wave Doppler ultrasonographic examinations were performed on nine nonpregnant and 56 normal pregnant women. The range of gestation was 6 to 40 weeks, and the objective was to record the renal arterial blood flow velocity waveform. Acceleration time and systolic per diastolic ratio of renal arterial blood flow velocity waveforms were assessed. Of 72 examinations, 68 recordings were made of the left renal artery (94.4%) and 28 of the right renal artery (38.9%), respectively. There was no correlation between acceleration time and systolic per diastolic ratio and gestational age, respectively, and no correlation between acceleration time and systolic per diastolic ratio, and caliceal diameter of the renal pelvis, respectively. Acceleration times of the left and right renal arteries were 47 +/- 11 and 40 +/- 8 msec in nonpregnant women and 62 +/- 23 and 62 +/- 23 msec in pregnant women, respectively. The left and right systolic per diastolic ratios were 3.1 +/- 0.7 and 2.9 +/- 0.5 in nonpregnant women and 2.8 +/- 0.6 and 2.6 +/- 0.5 in pregnant women, respectively. Therefore these data provide a foundation for the study of hydronephrosis, which may occur in pregnant women.