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The European Union (EU) recently ratcheted its climate ambition to net-zero emissions by 2050, with a milestone of 55% emissions cuts in 2030. This study carries out a model inter-comparison to assess the EU's path, from “Fit for 55” in 2030 to an intermediate milestone in 2040 and onto net zero in 2050, offering insights at sectoral and member-state levels. Our model results support the bloc's ambition for its Emissions Trading System and Effort Sharing Regulation sectors while pointing to the need for near-complete decarbonization of electricity by 2040, enabled by considerable deployment of renewables (45%–65% in 2030, to 60%–70% in 2040, and to 75%–90% in 2050 in electricity generation) and carbon capture and storage (0.5–2 GtCO2/year by 2050). We also highlight the trade-offs between supply-side and harder-to-abate sectors, assess the ambition of member states for net zero and timing of coal phaseout, and reflect on the economic implications of investment, technical, and policy needs. © 2023 The Author(s)

The Paris Agreement and the 2030 Agenda for Sustainable Development embody highly intertwined targets to act for climate in conjunction with sustainable development. This, however, entails different meanings and challenges across the world. Kenya, in particular, needs to address serious sustainability threats, like poverty and lack of modern and affordable energy access. This study uses a multi-criteria group decision aid and consensus measuring framework, to integrate both agendas, and engages with Kenyan stakeholders to help inform future mitigation research and policy in the country. Results showed that stakeholders highlight topics largely underrepresented in model-based mitigation analysis, such as biodiversity preservation and demand-side transformations, while pointing to gaps in cross-sectoral policies in relation to access to modern energy, agriculture, life on land, and climate change mitigation. With numerous past and recent policies aiming at these issues, persistent stakeholder concerns over these topics hint at limited success. Sectoral and technological priorities only recently emphasised in Kenyan policy efforts are also correlated with stakeholders' concerns, highlighting that progress is not only a matter of legislation, but also of coordination, consistency of targets, and comprehensibility. Higher bias is found among the preferences of stakeholders coming from the country's private sector. Results from this exercise can inform national policymakers on effectively reshaping the future direction of the country, as well as modelling efforts aimed at underpinning Kenya's energy, climate and sustainable development policy. © 2022 The Authors

Most of the integrated assessment modelling literature focuses on cost-effective pathways towards given temperature goals. Conversely, using seven diverse integrated assessment models, we project global energy CO2 emissions trajectories on the basis of near-term mitigation efforts and two assumptions on how these efforts continue post-2030. Despite finding a wide range of emissions by 2050, nearly all the scenarios have median warming of less than 3 °C in 2100. However, the most optimistic scenario is still insufficient to limit global warming to 2 °C. We furthermore highlight key modelling choices inherent to projecting where emissions are headed. First, emissions are more sensitive to the choice of integrated assessment model than to the assumed mitigation effort, highlighting the importance of heterogeneous model intercomparisons. Differences across models reflect diversity in baseline assumptions and impacts of near-term mitigation efforts. Second, the common practice of using economy-wide carbon prices to represent policy exaggerates carbon capture and storage use compared with explicitly modelling policies.

Harmonisation sets the ground to a solid inter-comparison of integrated assessment models. A clear and transparent harmonisation process promotes a consistent interpretation of the modelling outcomes divergences and, reducing the model variance, is instrumental to the use of integrated assessment models to support policy decision-making. Despite its crucial role for climate economic policies, the definition of a comprehensive harmonisation methodology for integrated assessment modelling remains an open challenge for the scientific community. This paper proposes a framework for a harmonisation methodology with the definition of indispensable steps and recommendations to overcome stumbling blocks in order to reduce the variance of the outcomes which depends on controllable modelling assumptions. The harmonisation approach of the PARIS REINFORCE project is presented here to layout such a framework. A decomposition analysis of the harmonisation process is shown through 6 integrated assessment models (GCAM, ICES-XPS, MUSE, E3ME, GEMINI-E3, and TIAM). Results prove the potentials of the proposed framework to reduce the model variance and present a powerful diagnostic tool to feedback on the quality of the harmonisation itself. © 2021

Isolated intrauterine growth restriction (IUGR) and preeclampsia (PE) share common placental pathogenesis. Differently from IUGR, PE is a systemic disorder which may also affect liver and brain. Early diagnosis of these conditions may optimize maternal and fetal management. Aim of this study was to assess whether Epidermal Growth Factor-Like domain 7 (EGFL7) dosage in maternal blood discriminates between isolated IUGR and PE. A total of 116 women were enrolled in this case–control study: 12 non-pregnant women, 34 healthy pregnant women, 34 women presenting with isolated IUGR and 36 presenting with PE. Levels of circulating EGFL7 and other known pro- and anti-angiogenic factors were measured by ELISA at different gestational ages (GA). Between 22–25 weeks of gestation, EGFL7 levels in early-onset PE (e-PE) plasma samples were significantly higher than those measured in controls or isolated IUGR samples (69.86 ± 6.17 vs. 19.8 ± 2.5 or 18.8 ± 2.8 µg/ml, respectively). Between 26–34 weeks, EGFL7 levels remained significantly higher in e-PE compared to IUGR. At term, circulating and placental EGFL7 levels were comparable between IUGR and late-onset PE (l-PE). In contrast, circulating levels of PlGF were decreased in both IUGR- and PE- complicated pregnancies, while levels of both sFLT-1 and sENDOGLIN were increased in both conditions. In conclusion, EGFL7 significantly discriminates between isolated IUGR and PE.

Recent calls to do climate policy research with, rather than for, stakeholders have been answered in non-modelling science. Notwithstanding progress in modelling literature, however, very little of the scenario space traces back to what stakeholders are ultimately concerned about. With a suite of eleven integrated assessment, energy system and sectoral models, we carry out a model inter-comparison for the EU, the scenario logic and research questions of which have been formulated based on stakeholders' concerns. The output of this process is a scenario framework exploring where the region is headed rather than how to achieve its goals, extrapolating its current policy efforts into the future. We find that Europe is currently on track to overperforming its pre-2020 40% target yet far from its newest ambition of 55% emissions cuts by 2030, as well as looking at a 1.0 2.35 GtCO2 emissions range in 2050. Aside from the importance of transport electrification, deployment levels of carbon capture and storage are found intertwined with deeper emissions cuts and with hydrogen diffusion, with most hydrogen produced post-2040 being blue. Finally, the multi-model exercise has highlighted benefits from deeper decarbonisation in terms of energy security and jobs, and moderate to high renewables-dominated investment needs. © 2021 The Authors

Decidualization is characterized by a series of genetic, metabolic, morphological, biochemical, vascular and immune changes occurring in the endometrial stroma in response to the implanting embryo or even before conception and involves the stromal cells of the endometrium. It is a fundamental reproductive event occurring in mammalian species with hemochorial placentation. A growing body of experimental and clinical evidence strongly suggests that defective or disrupted decidualization contributes to the establishment of an inappropriate maternal-fetal interface. This has relevant clinical consequences, ranging from recurrent implantation failure and recurrent pregnancy loss in early pregnancy to several significant complications of advanced gestation. Moreover, recent evidence indicates that selected diseases of the endometrium, such as chronic endometritis and endometriosis, can have a detrimental impact on the decidualization response in the endometrium and may help explain some aspects of the reduced reproductive outcome associated with these conditions. Further research efforts are needed to fully understand the biomolecular mechanisms ans events underlying an abnormal decidualization response. This will permit the development of new diagnostic and therapeutic strategies aimed to improve the likelihood of achieveing a successful pregnancy.

Intrauterine growth restriction (IUGR) is a pathological condition of pregnancy with high perinatal mortality and morbidity, characterized by inadequate fetal growth associated to altered maternal hemodynamics with impaired uteroplacental blood flow and placental insufficiency. To date, iatrogenic premature delivery remains the elective therapeutic strategy. However, in recent years the possibility of a therapeutic approach with vasodilators and myorelaxants, such as nitric oxide (NO) donors, has gained interest. NO controls many endothelial cell functions, including angiogenesis and vascular permeability, by regulating the expression of angiogenic factors, such as Vascular Endothelial Growth Factor. In the present study, we investigated if treatment of pregnancies complicated by IUGR with NO donors affects the expression of Epidermal Growth Factor-Like Domain 7 (EGFL7), a secreted endothelial factor, previously demonstrated to be expressed by both endothelial and trophoblast cells and involved in proper placental development. NO donor treatment induced placental levels of EGFL7 and, in association with oral fluids, significantly improved fetal growth. Ex vivo experiments confirmed that NO donors increased expression and secretion of EGFL7 by villous explants. To specifically investigate the potential response of trophoblast cells to NO, we treated HTR8-sVneo cells with NO donors and observed induction of EGFL7 expression. Altogether, our findings indicate that NO induces endothelial and trophoblast expression of EGFL7 in the placenta and improves fetal growth, suggesting a correlation between placental levels of EGFL7 and pregnancy outcome.

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.

A simple approach is reported to engineer biodegradable and biocompatible nanoporous hyaluronic acid particles (NPHAs) with a characteristic sponge‐like morphology and uniform size. These NPHAs can be synthesized using the concomitant cross‐linking of hyaluronic acid and the cross‐linking agent precipitation. The nanoporous architecture of NPHAs prevents the rapid enzymatic degradation of hyaluronic acid and controls the erosion of microparticles in physiological conditions. Once injected into an intra‐articular body cavity of healthy mice, these NPHAs reside at the point‐of‐delivery for an extended time period, exhibiting a sustained release of hyaluronic acid. In addition, in vivo studies indicate the persistence of NPHAs in the knee joints with neither accumulation into major organs, nor any local or systemic side‐effect. The use of NPHAs is emphasized as reservoirs of hyaluronic acid, effectively providing an innovative and safe platform for prolonging the favorable effects displayed by hyaluronic acid on joints affected by osteoarthritis.

At present, Europe lacks innovative companies, which grow quickly and end up big. This book examines SME growth, innovation and success, to suggest that fast-growing firms could offer a major contribution to the recovery of a European economy. The contributors examine eleven case studies from Italian firms, breaking the book up into three parts: context, actors and strategy. The topics discussed include entrepreneurship and technological clusters, innovative start-ups and growth factors, and family firms as the incubators of new ventures. Students and scholars of entrepreneurship and other related disciplines will find this book to be of interest. It will also be of use to practitioners in the field, working with and alongside SMEs.

Epidermal growth factor-like domain 7 (Egfl7) is a gene that encodes a partially secreted protein and whose expression is largely restricted to the endothelia. We recently reported that EGFL7 is also expressed by trophoblast cells in mouse and human placentas. Here, we investigated the molecular pathways that are regulated by EGFL7 in trophoblast cells. Stable EGFL7 overexpression in a Jeg3 human choriocarcinoma cell line resulted in significantly increased cell migration and invasiveness, while cell proliferation was unaffected. Analysis of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways showed that EGFL7 promotes Jeg3 cell motility by activating both pathways. We show that EGFL7 activates the epidermal growth factor receptor (EGFR) in Jeg3 cells, resulting in downstream activation of extracellular regulated kinases (ERKs). In addition, we provide evidence that EGFL7-triggered migration of Jeg3 cells involves activation of NOTCH signaling. EGFL7 and NOTCH1 are co-expressed in Jeg3 cells, and blocking of NOTCH activation abrogates enhanced migration of Jeg3 cells overexpressing EGFL7. We also demonstrate that signaling through EGFR and NOTCH converged to mediate EGFL7 effects. Reduction of endogenous EGFL7 expression in Jeg3 cells significantly decreased cell migration. We further confirmed that EGFL7 stimulates cell migration by using primary human first trimester trophoblast (PTB) cells overexpressing EGFL7. In conclusion, our data suggest that in trophoblast cells, EGFL7 regulates cell migration and invasion by activating multiple signaling pathways. Our results provide a possible explanation for the correlation between reduced expression of EGFL7 and inadequate trophoblast invasion observed in placentopathies.

Leptin is an adipocytokine that reduces ischemic damage in several organs including brain and heart. STAT3 activation is a key step for the attainment of leptin effects in various tissues. We evaluated the possible effect of leptin on liver viability and STAT3 activation, in a rat model of ischemia-reperfusion injury. Rat livers, flushed and stored with Belzer solution (4° C for 24 h), were warmly reperfused (3.5 ml/min/g liver for 1 h at 37°C with O 2) with Krebs-Ringer bicarbonate. Treatment group underwent an identical protocol with the adjunct of Leptin (10 ng/ml). Liver effluent was harvested to assess LDH and AST output. Liver tissue was used for pSTAT3 expression (western blot and immunostaining), optical microscopy, TUNEL, and Cell Death Detection assays. The pSTAT3 expression was enhanced by administration of leptin. In parallel, LDH and AST output were reduced (P = 0.04 and P = 0.02 for LDH and AST, respectively). Optical microscopy, TUNEL, and Cell Death Detection assay results demonstrated increased viability in livers treated with leptin in comparison with others (Optical microscopy P = 0.02; TUNEL P = 0.01; Cell death Detection assay P = 0.003). In conclusion, cold storage and reperfusion with leptin reduce liver ischemia-reperfusion injury. This effect is associated with an increased expression of pSTAT-3. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Carbon nanotubes (CNTs) are among the most relevant engineered nanomaterials (ENMs). Given the expected rise of exposure to ENMs, there is concern that they may adversely affect health of exposed people. Aim of the study was to test the hypothesis that single wall carbon nanotubes (SWCNTs) pulmonary exposure acutely affect the autonomic cardiovascular regulation in conscious rats. We studied Wistar-Kyoto rats in which a telemetry transmitter for continuous arterial pressure (AP) and heart rate (HR) recordings was surgically implanted. SWCNTs dispersed in phosphate buffer saline (PBS) or PBS alone were randomly administered intratracheally. Immediately before, and 24 hours after each instillation a 30 min AP recording was performed. The sequence analysis was performed to evaluate the baroreflex function. In the control group, PBS instillation did not induce any significant changes. At variance the SWCNT exposure induced a significant reduction of baroreflex system (BRS) (3.5 ± 0.6 versus 2.6 ± 0.40 msec/mmHg) without significant changes in the occurrence of baroreflex sequences (7.5 ± 0.47 % versus 7.4 ± 0.38 %). Our results show that SWCNT pulmonary exposure might affect the cardiovascular autonomic regulation thus contributing to cardiac and arrhythmic events.

Objectives: Implantation and placental development are essential for the patterning of the embryo, for its growth and survival upon implantation, as well as for preserving the health of the fetus and mother. Inadequate invasion of trophoblast cells into the maternal decidua and the deficient growth of fetal blood vessels are actually recognized as possible pathogenetic factors of preeclampsia (PE). To examine molecular mechanisms that control these events, we are focusing in our studies on the endothelial gene Egfl7. Our preliminary studies show that Egfl7 has a critical role in molecular processes that control human vascular development and proper placental implantation: in particular, Egfl7 is expressed in the trophectoderm and in the fetal placental vasculature. To assess the involvement of Egfl7 in the development of PE, we investigate the EGFL7 expression patterns between PE and control placentas. Materials and Methods: Two study groups are considered: (1) a first of women with pregnancies complicated by early onset PE ; (2) a second study group of healthy women. The placental biopsies were obtained immediately after caesarean section from both groups, the PE patients and the normal controls. Real-time PCR and immunofluorescence analysis of EGFL7 expression in normal and preeclamptic human placental tissue were performed. Results: Real-time PCR analysis revealed that EGFL7 is strongly down regulated in the villi of PE placentas when compared to normal samples. In agreement with published data, VEGF expression was also decreased in PE placentas, although to a lesser extent compared to EGFL7. At variance, expression of the pan-endothelial marker CD31 was not significantly altered in PE as compared to normal placentas. These results were confirmed by immunofluorescence analysis. Conclusion: Our results suggest a role for Egfl7 in the pathogenesis of PE. We hypothesize that in PE placental villi the total number of endothelial cells is not significantly decreased (