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Substance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis. We also additionally describe two longitudinal cohorts — the Brisbane Longitudinal Twin Study in Australia and the Lifelines Cohort Study in the Netherlands. By applying the methodological framework to these two unique datasets, our future research will explore the complex interplay between genetic factors, gene expression, and environmental influences on substance use behaviors and disorders across different life stages and populations.
Real estate is a major component of China’s national wealth, serving as a key store of value. Property taxes potentially influence households’ belief in the stability of the housing market, resulting in varying effects of such taxes. This paper constructs an equilibrium model of stores of value to examine these effects under diverse beliefs. The results show that property taxes can constrain the growth of housing prices if households maintain their belief in the future stability of housing values. However, damaging this belief would lead to a safety trap with a decline in output. The paper also demonstrates that using tax revenue to finance government bond issuance can be an effective way to lower housing prices and increase output.
To investigate the effects of co-infection with Clonorchis sinensis (C. sinensis) on T cell exhaustion levels in patients with chronic hepatitis B, we enrolled clinical cases in this study, including the patients with concomitant C. sinensis and HBV infection. In this study, we detected inhibitory receptors and cytokine expression in circulating CD4+ and CD8+ T cells by flow cytometry. PD-1 and TIM-3 expression levels were significantly higher on CD4+ T and CD8+ T cells from co-infected patients than on those from the HBV patients. In addition, CD4+ T cells and CD8+ T cells function were significantly inhibited by C. sinensis and HBV co-infection compared with HBV single infection, secreting lower levels of Interferon gamma (IFN-γ), Interleukin-2 (IL-2), and TNF-α. Our current results suggested that C. sinensis co-infection could exacerbate T cell exhaustion in patients with chronic hepatitis B. PD-1 and TIM-3 could be novel biomarkers for T cell exhaustion in patients with Clonorchis sinensis and chronic hepatitis B co-infection. Furthermore, it may be one possible reason for the weaker response to antiviral therapies and the chronicity of HBV infection in co-infected patients. We must realize the importance of C. sinensis treatment for HBV-infected patients. It might provide useful information for clinical doctors to choose the right treatment plans.
Here, we report the generation of MeV alpha-particles from H-11B fusion initiated by laser-accelerated boron ions. Boron ions with maximum energy of 6 MeV and fluence of 109/MeV/sr@5 MeV were generated from 60 nm-thick self-supporting boron nanofoils irradiated by 1 J femtosecond pulses at an intensity of 1019 W/cm2. By bombarding secondary hydrogenous targets with the boron ions, 3 × 105/sr alpha-particles from H-11B fusion were registered, which is consistent with the theoretical yield calculated from the measured boron energy spectra. Our results demonstrated an alternative way toward ultrashort MeV alpha-particle sources employing compact femtosecond lasers. The ion acceleration and product measurement scheme are referential for the studies on the ion stopping power and cross section of the H-11B reaction in solid or plasma.
This study aims to understand the epidemiological characteristics of SARS-CoV-2 infection in the paediatric population during the outbreak of the Omicron variant in Shanghai. We retrospectively analysed the population-based epidemiological characteristics and clinical outcome of SARS-CoV-2 Omicron variant infection in children in Minhang District, Shanghai, based on the citywide surveillance system during the outbreak period in 2022 (March to May). During this time, a total of 63,969 cases of SARS-CoV-2 infection were notified in Minhang District, out of which 4,652 (7.3%) were children and adolescents <18 years. The incidence rate of SARS-CoV-2 infections in children was 153 per 10,000. Of all paediatric cases, 50% reported to be clinically symptomatic within 1–3 days after PCR confirmation by parents or themselves, with 36.3% and 18.9% of paediatric cases reporting fever and cough. Also, 58.4% of paediatric cases had received at least one dose of the COVID-19 vaccine and 52.1% had received two doses of the COVID-19 vaccination. Our findings are informative for the implementation of appropriate measures to protect children from the threat of SARS-CoV-2 infection.
Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.
Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.
The EU’s latest decision on adopting the recovery fund was revolutionary, both quantitatively and qualitatively. It would also dominate the EU’s economic governance of the decade of the 2020s. This article is an attempt to evaluate whether the EU’s recovery fund was the right policy answers to the post-COVID-19 EU economy or not, and explore its meanings and implications for European integration. This article argues that COVID-19 hit the EU at a time of health and social precariousness, and proved the conventional economic governance unsustainable. Necessities for game-changing in the post-COVID-19 economic governance were justified on both practical and moral grounds. Judging with these yardsticks, the EU’s recovery fund was evaluated as a welcomed paradigm shift in both the ideology and methodology of its economic governance. Beyond a contemporary economic rescue package, the recovery fund implied laying the cornerstone of completing a fiscal union in the Eurozone, for enhancing institutional functions of the European Commission, and for rediscovering the nature of European integration as the rescuer of national states, through the newly-forming consensus between Eurosceptic nationalists and pro-EU integrationists. This article reminds us that the COVID-19 crisis was a crucial opportunity for EU leadership to legitimize the EU’s existence in the post-Brexit era. If well implemented, the recovery fund could usher in a new chapter of European integration. If it fails, European integration would be at risk of further fragmentation and entrench into an ever-stronger anti-EU populism.
With the rapid rise in the prevalence of non-tuberculous mycobacteria (NTM) diseases across the world, the microbiological diagnosis of NTM isolates is becoming increasingly important for the diagnosis and treatment of NTM disease. In this study, the clinical presentation, species distribution and drug susceptibility of patients with NTM disease visiting the Chongqing Public Health Medical Centre during March 2016–April 2019 were retrospectively analysed. Among the 146 patients with NTM disease, eight NTM species (complex) were identified. The predominant NTM species in these patients were identified to be Mycobacterium abscessus complex (53, 36.3%), M. intracellulare (38, 26%) and M. fortuitum (17, 11.7%). In addition, two or more species were isolated from 7.5% of the patients. Pulmonary NTM disease (142, 97.3%) showed the highest prevalence among the patients. It was observed that 40.1% of the patients with pulmonary NTM disease had chronic pulmonary obstructive disease and bronchiectasis, while 22.5% had prior tuberculosis. Male patients showed more association with the conditions of cough and haemoptysis than the female patients. In an in vitro antimicrobial susceptibility testing, most of the species showed susceptibility to linezolid, amikacin and clarithromycin, while M. fortuitum exhibited low susceptibility to tobramycin. In conclusion, the prevalence of NTM disease, especially that of the pulmonary NTM disease, is common in Southwest China. Species identification and drug susceptibility testing are thus extremely important to ensure appropriate treatment regimens for patient care and management.
A detailed electron backscatter diffraction (EBSD) characterization was utilized to investigate abnormal grain growth behavior of nanocrystalline (NC) Au films constrained by a flexible substrate under cyclic loading. Abnormally grown grains (AGGs) in front of about 15 fatigue cracks were picked out to investigate the grain reorientation behavior during abnormal grain growth in the fatigue crack tip in the cyclically deformed thin films. It shows that the AGGs exhibited 〈001〉 orientation along the loading direction, whereas grains grown far away from fatigue cracks had no significant texture change. The cyclic cumulative shear strain was found to play a key role in grain reorientation. A lattice rotation model was proposed to elucidate the grain reorientation mechanism during abnormal grain growth. Such grain reorientation behavior of NC metals was found to provide an intrinsic resistance of the NC metals to fatigue damage.
In order to reveal the quantitative relationship between fatigue crack deflection path and cross-sectional grain boundary (GB) arrangement of metallic nanolayered composites (NLCs), a stochastic model was established based on the interface-dominant fatigue damage for the ultrafine-scale NLCs. The model indicates that the crack deflection length decreases with decreasing GB arrangement deviation and grain size of constituent layers. The observation and quantitative analysis of fatigue cracking behavior of the Cu/W multilayers with a layer thickness of 5 and 20 nm was conducted to verify the model.
Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.
Fatigue performance of metallic nanolayered composites (NLCs) has been gaining more and more attention due to the rapid development in the field of both micro-electro-mechanical systems and high-performance engineering structure materials and the increasing demand for long-term fatigue reliability. Metallic NLCs have exhibited different damage behaviors due to the effect of high-density heterogeneous interface compared with bulk materials and thin metal films. In this review paper, the cyclic deformation damage behavior, fatigue cracking feature, and fatigue properties of some metallic NLCs are reviewed. Effects of length scales, including layer thickness and grain size, on fatigue damage behaviors of the NLCs are revealed, and the transition of the fatigue cracking behavior and the corresponding damage mechanism are discussed. Then, the fatigue properties of some typical metallic NLCs are presented and compared with that of bulk materials and metal thin films. The effect of interface type and grain boundary alignment is also discussed to correlate with fatigue cracking resistance of the NLCs. Finally, some prospective research topics on fatigue performance of metallic NLCs are addressed.
Fatigue properties of Mo/W multilayers with individual layer thickness (λ) of 5, 20, 50 and 100 nm on flexible polyimide substrates were investigated. The experimental results show that the fatigue resistance increases with decreasing λ from 100 nm to 20 nm, and reaches the maximum at λ=20 nm, and then decreases when further decreasing λ. Fatigue cracks of Mo/W multilayers with different λ were found to propagate along columnar grain boundary in the out-of-plane direction and along the boundary of cluster structures. The enhanced fatigue resistance is attributed to the larger cluster inclination angles and the more tortuous in-plane cracking paths.
With the development of remote sensing and geostatistical technology, complex environmental variables are increasingly easily quantified and applied in modelling soil organic carbon (SOC). However, this emphasizes data redundancy and multicollinearity problems adding to the difficulty in selecting dominant influential auxiliary variables and uncertainty in estimating SOC stocks. The current paper considers the spatial characteristics of SOC density (SOCD) to construct prediction models of SOCD on the basis of reducing the data dimensionality and complexity using the principal component analysis (PCA) method. A total of 260 topsoil samples were collected from Chahe town, China. Eight environmental variables (elevation, aspect, slope, normalized difference vegetation index, normalized difference moisture index, nearest distance to construction area and road, and land use degree comprehensive index) were pre-analysed by PCA and then extracted as the main principal component variables to construct prediction models. Two geostatistical approaches (ordinary kriging and ordinary co-kriging) and two regression approaches (ordinary least squares and geographically weighted regression (GWR)) were used to estimate SOCD. Results showed that PCA played an important role in reducing the redundancy and multicollinearity of the auxiliary variables and GWR achieved the highest prediction accuracy in these four models. GWR considered not only the spatial characteristics of SOCD but also the related valuable information of the auxiliary attributes. In summary, PCA-GWR is a promising spatial method used here to predict SOC stocks.
This article is an attempt to clarify the effects of the German labour market reforms, commonly known as the Hartz reforms. Competing arguments were used to identify the welfare implications for German society and the German economy in order to explore whether or not such labour market reforms might provide another German answer, following fiscal discipline, to the EU’s post-euro-crisis management. This paper confirms that the Hartz reforms effectively reduced German unemployment, but they did not fundamentally solve the problem. Moreover, such effects appeared to propagate an increase in size of the low-paid sector, declining wages and increasing income inequality. The reforms were not welfare-enhancing for individuals because of increased poverty levels in employment and unemployment, which further implied a counter-productive risk for the German economy because of the contraction of domestic consumption, and potential social instability for German society because of rising inequality and deteriorating living standards. Therefore, Hartz-style reforms are neither a desirable model for other EU countries, nor the answer to Europe’s post-euro-crisis management in a time of fiscal austerity and negative interest rates. The real danger to European integration, as argued in this article, is not the challenge from high unemployment, but from Germany’s complacency of a one-size-fits-all thinking and, being the EU’s leading country, its double standards towards and ignorance of the differential nature and contexts of the European unemployment issue compared with the German one. This article warns that the mishandling of labour market reforms could result in the collapse of the already fragile public confidence in European integration.
We present for the first time the feasibility to recover the stiffness (here shear modulus) distribution of a three-dimensional heterogeneous sample using measured surface displacements and inverse algorithms without making any assumptions about local homogeneities and the stiffness distribution. We simulate experiments to create measured displacements and augment them with noise, significantly higher than anticipated measurement noise. We also test two-dimensional problems in plane strain with multiple stiff inclusions. Our inverse strategy recovers the shear modulus values in the inclusions and background well, and reveals the shape of the inclusion clearly.
On the eve of 60th anniversary of the Treaty of Rome, the UK voted to withdraw from the EU (so-called Brexit). The implications for European integration and EU policies are far from clear and require further investigation. This paper aims to answer: what does Brexit imply for European integration? What messages were sent to the EU from the UK referendum? Did EU leaders interpret these messages and implications correctly and did they respond with the right policy? After examining the competing interpretations, this paper argues that the sharp divisions between different socio-economic classes shown in voting behaviour highlight the imperative of addressing economic inequality and distributive injustice, which are rooted in the structural flaws of EU governance and have been aggravated by the mismanagement of the Euro crisis. To move European integration forward and to keep a ‘political Europe’ sustainable, a ‘social Europe’ making an ‘economic Europe’ more inclusive and fair is required.
Stretchability of polyimide-supported nanocrystalline Au films with a thickness ranging from 930 to 20 nm was evaluated by uniaxial tensile testing. The results show that the fracture strain gradually decreased with decreasing the film thickness. Such degraded stretchability depends on plastic deformation mechanisms associated with the length scales. As the film thickness is larger than 90 nm, local thinning in the grown grains contributed to the high stretchability. Full dislocation behaviors including dislocation pileup in the 930 nm-thick film, the activation of Frank–Read dislocation source in the 170 nm-thick film and the grain boundary dislocation source in the 90 nm-thick film were dominated plastic deformation. As the film thickness is less than 40 nm, low stretchability of thin films resulted from intergranular fracture, and partial dislocation behaviors became prevailed. Evident grain growth happened in the films studied except for the 20 nm-thick film, which is expected to be involved in the stretchability of the nanocrystalline metal films on flexible substrates.
We examined the in vitro developmental competence of parthenogenetic activation (PA) oocytes activated by an electric pulse (EP) and treated with various concentrations of AZD5438 for 4 h. Treatment with 10 µM AZD5438 for 4 h significantly improved the blastocyst formation rate of PA oocytes in comparison with 0, 20, or 50 µM AZD5438 treatment (46.4% vs. 34.5%, 32.3%, and 24.0%, respectively; P < 0.05). The blastocyst formation rate was higher in the group treated with AZD5438 for 4 h than in the groups treated with AZD5438 for 2 or 6 h (42.8% vs. 38.6% and 37.2%, respectively; P > 0.05). Furthermore, 66.67% of blastocysts derived from these AZD5438-treated PA oocytes had a diploid karyotype. The blastocyst formation rate of PA and somatic cell nuclear transfer (SCNT) embryos was similar between oocytes activated by an EP and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP and treated with 10 µM AZD5438 for 4 h (11.11% vs. 13.40%, P > 0.05). In addition, the level of maturation-promoting factor (MPF) was significantly decreased in oocytes activated by an EP and treated with 10 µM AZD5438 for 4 h. Finally, the mRNA expression levels of apoptosis-related genes (Bax and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by RT-PCR; however, there were no differences between the AZD5438-treated and non-treated control groups. Our results demonstrate that porcine oocyte activation via an EP in combination with AZD5438 treatment can lead to a high blastocyst formation rate in PA and SCNT experiments.