Newborn dried blood spots for serologic surveys of COVID-19

There is an urgent need for inexpensive, population-wide surveillance testing for COVID-19. We tested newborn dried blood spot (DBS) anti-SARS-CoV-2 antibodies for all infants born at Yale from March to May 2020, and found that newborn DBS serologies reflect maternal and population-wide infection rates during the study period. This suggests a role for DBS in COVID-19 surveillance in areas where viral testing is limited

Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling

Severe acute respiratory syndrome–coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart of therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to the virus’s inability to use the mouse orthologue of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis, these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno-associated virus (AAV)–mediated expression of hACE2. These mice support viral replication and exhibit pathological findings found in COVID-19 patients. Moreover, we show that type I interferons do not control SARS-CoV-2 replication in vivo but are significant drivers of pathological responses. Thus, the AAV-hACE2 mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds

Green development performance of water resources and its economic-related determinants

In the context of severe water shortage and pollution, enhancing the green total-factor productivity of water resources (GTFPWR) is critical for the green development of water resources. This study aims to propose a novel two-stage analytical framework, in which the GTFPWR is measured in the first stage and its economic-related determinants are examined in the second stage. In this two-stage analytical framework, we improve and integrate four classical methods, namely, the undesirable-super-slack-based measure, global Malmquist-Luenberger productivity index, system generalized method of moments and fixed-effects panel threshold models. The proposed analytical framework is capable of addressing four practical issues simultaneously: equal efficiency, undesirable outputs, impact scenarios and endogenous biases. We can thus more accurately and comprehensively evaluate the GTFPWR and its determinants. To validate the applicability and suitability of the proposed methodology, we collected the panel data about water resources across 30 provinces in China from 2005 to 2015 for an empirical study. The main findings of this study are as follows: i) the level of water utilization is a critical factor for the government to decide whether to increase the GTFPWR via foreign direct investment and trade; ii) the amount of wastewater should be effectively reduced to mitigate the conflicts between urbanization and the GTFPWR growth; iii) inland provinces, particularly Shanxi, Hainan and Yunnan, need to improve water technologies and management to increase their low-GTFPWR-growth rates. Our analytical framework is practical to evaluate water-use productivity and its determinants, while our empirical findings provide new insights into the green development of water resources and may shed light on future policies of environmental management

NUPR1 is a critical repressor of ferroptosis

International audienceFerroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Transcription factors play multiple roles in ferroptosis, although the key regulator for ferroptosis in iron metabolism remains elusive. Using NanoString technology, we identify NUPR1, a stress-inducible transcription factor, as a driver of ferroptosis resistance. Mechanistically, NUPR1-mediated LCN2 expression blocks ferroptotic cell death through diminishing iron accumulation and subsequent oxidative damage. Consequently, LCN2 depletion mimics NUPR1 deficiency with respect to ferroptosis induction, whereas transfection-enforced re-expression of LCN2 restores resistance to ferroptosis in NUPR1-deficient cells. Pharmacological or genetic blockade of the NUPR1-LCN2 pathway (using NUPR1 shRNA, LCN2 shRNA, pancreas-specific Lcn2 conditional knockout mice, or the small molecule ZZW-115) increases the activity of the ferroptosis inducer erastin and worsens pancreatitis, in suitable mouse models. These findings suggest a link between NUPR1-regulated iron metabolism and ferroptosis susceptibility

Innovation-driven industrial green development: The moderating role of regional factors

Industrial green development (IGD) is a critical response to the over-consumption of natural resources and pollution caused by modern industry. Innovation-driven IGD has generated great interest in recent years. However, relatively less attention has been paid to the various aspects of IGD and the moderating role of regional factors, including the developmental stage of IGD, government-scale, and enterprise-scale. The present study was conducted to fill these research gaps using panel data across 30 provinces in China from 2005 to 2015. The empirical results show that 1) innovation does promote IGD and is most effective in low-carbon production, followed by resource reduction, economic operation, and pollution abatement; 2) there is an inverted U-shaped relationship between the regional IGD level and the role of innovation in IGD; and 3) both government-scale and enterprise-scale contribute to the innovation-driven IGD. These findings provide new insights into the impact of innovation on IGD and may shed light on future decisions related to green development

PDK4 dictates metabolic resistance to ferroptosis by suppressing pyruvate oxidation and fatty acid synthesis

International audienceAlthough induction of ferroptosis, an iron-dependent form of non-apoptotic cell death, has emerged as an anticancer strategy, the metabolic basis of ferroptotic death remains poorly elucidated. Here, we show that glucose determines the sensitivity of human pancreatic ductal carcinoma cells to ferroptosis induced by pharmacologically inhibiting system xc-. Mechanistically, SLC2A1-mediated glucose uptake promotes glycolysis and, thus, facilitates pyruvate oxidation, fuels the tricyclic acid cycle, and stimulates fatty acid synthesis, which finally facilitates lipid peroxidation-dependent ferroptotic death. Screening of a small interfering RNA (siRNA) library targeting metabolic enzymes leads to identification of pyruvate dehydrogenase kinase 4 (PDK4) as the top gene responsible for ferroptosis resistance. PDK4 inhibits ferroptosis by blocking pyruvate dehydrogenase-dependent pyruvate oxidation. Inhibiting PDK4 enhances the anticancer activity of system xc- inhibitors in vitro and in suitable preclinical mouse models (e.g., a high-fat diet diabetes model). These findings reveal metabolic reprogramming as a potential target for overcoming ferroptosis resistance

Newborn Dried Blood Spots for Serologic Surveys of COVID-19

There is an urgent need for inexpensive, population-wide surveillance testing for COVID-19. We tested newborn dried blood spot (DBS) anti-SARS-CoV-2 antibodies for all infants born at Yale from March to May 2020, and found that newborn DBS serologies reflect maternal and population-wide infection rates during the study period. This suggests a role for DBS in COVID-19 surveillance in areas where viral testing is limited

Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling

Severe acute respiratory syndrome–coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart of therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to the virus’s inability to use the mouse orthologue of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis, these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno-associated virus (AAV)–mediated expression of hACE2. These mice support viral replication and exhibit pathological findings found in COVID-19 patients. Moreover, we show that type I interferons do not control SARS-CoV-2 replication in vivo but are significant drivers of pathological responses. Thus, the AAV-hACE2 mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds