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

Kynurenic acid may underlie sex-specific immune responses to COVID-19

Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males

Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells. Sema4C on TFH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases TFH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimize antibody responses.This work was funded partly by the Ministry of Science and Technology 973 program (grant 2014CB542501 to H.Q.), the National Natural Science Foundation of China (grants 81425011 and 81330070 to H.Q. and grant 31200670 to L.W.), the Ministry of Science and Technology 863 program (grant 2012AA022403 to L.W.), a China Postdoctoral Science Foundation grant (2013M540970 to L.W.), and the Tsinghua-Peking Center for Life Sciences. H.Q. was supported partly by a Bayer Endowed Chair Professorship

Dynamic Evolution of High-Quality Economic Development Levels: Regional Differences and Distribution in West China

A comprehensive and scientific system for measuring the quality of economic development will provide the basis for and guarantee high-quality economic development (HQED) in China. In this paper, we constructed an indicator-evaluating system for the high-quality development of the western region’s economy according to a new development concept and the relevant requirements of western development and measured the composite index and sub-dimension index of its HQED from 2000 to 2020 using the entropy method; revealed the regional differences and sources of western HQED using the Dagum Gini index (GI) decomposition method; and analyzed the evolution of HQED using kernel density estimation and the Markov probability transfer matrix. The study showed that western HQED was on the rise year by year, but there was a large gap between the 11 provinces, characterized by “high in the middle and low on the edge” values in general; inter-regional differences constituted the main source of overall differences; and western HQED showed “club convergence” in a steady state, with upward shifts more likely than downward shifts

Evaluating the impact of China's MSW sorting pilot policy on urban sustainable development: Empirical evidence from 95 cities.

The escalating challenge of municipal solid waste (MSW) critically tests the sustainable development capacities of urban centers. In response, China initiated pilot policies in 2017 aimed at bolstering MSW management. The effectiveness of these initiatives, however, necessitates empirical scrutiny. This study leverages panel data spanning 95 cities at the prefectural level or higher, covering the period from 2006 to 2020, to assess the impact of the MSW sorting pilot policy on urban sustainable development using a difference-in-differences approach. The research found that the MSW sorting pilot policy has significantly increased the processing volume of MSW, thereby enhancing the sustainable development capabilities of cities. Further, the study identifies augmented fixed asset investments as a key mechanism through which pilot cities have enhanced their MSW management capabilities. Notably, the policy's stimulative effects are more pronounced in less densely populated and economically lagging regions. These findings provide critical insights for developing nations in shaping MSW sorting strategies and advancing urban sustainability

Placebo looped 500 times.

The escalating challenge of municipal solid waste (MSW) critically tests the sustainable development capacities of urban centers. In response, China initiated pilot policies in 2017 aimed at bolstering MSW management. The effectiveness of these initiatives, however, necessitates empirical scrutiny. This study leverages panel data spanning 95 cities at the prefectural level or higher, covering the period from 2006 to 2020, to assess the impact of the MSW sorting pilot policy on urban sustainable development using a difference-in-differences approach. The research found that the MSW sorting pilot policy has significantly increased the processing volume of MSW, thereby enhancing the sustainable development capabilities of cities. Further, the study identifies augmented fixed asset investments as a key mechanism through which pilot cities have enhanced their MSW management capabilities. Notably, the policy’s stimulative effects are more pronounced in less densely populated and economically lagging regions. These findings provide critical insights for developing nations in shaping MSW sorting strategies and advancing urban sustainability.</div

A Review of Risk Assessment Methods for Power System

In view of the current social background of power system becoming more and more complicated, and the current research situation of related fields, this paper discusses the common methods of power system risk assessment, including the method of hierarchy analysis, Markov chain model, Monte Carlo method, fuzzy comprehensive evaluation and related research progress. The advantages and disadvantages of the four methods are enumerated respectively. It is considered that the power system should be evaluated synthetically in the practical application and the effective risk assessment method should be adopted rationally

Heterogeneity test: Economic scale.

The escalating challenge of municipal solid waste (MSW) critically tests the sustainable development capacities of urban centers. In response, China initiated pilot policies in 2017 aimed at bolstering MSW management. The effectiveness of these initiatives, however, necessitates empirical scrutiny. This study leverages panel data spanning 95 cities at the prefectural level or higher, covering the period from 2006 to 2020, to assess the impact of the MSW sorting pilot policy on urban sustainable development using a difference-in-differences approach. The research found that the MSW sorting pilot policy has significantly increased the processing volume of MSW, thereby enhancing the sustainable development capabilities of cities. Further, the study identifies augmented fixed asset investments as a key mechanism through which pilot cities have enhanced their MSW management capabilities. Notably, the policy’s stimulative effects are more pronounced in less densely populated and economically lagging regions. These findings provide critical insights for developing nations in shaping MSW sorting strategies and advancing urban sustainability.</div