A novel function of CREG in metabolic disorders

Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment. Cellular repressor of E1A-stimulated genes (CREG) is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature, homeostatic state. Recently, CREG turns to be an important mediator in the development of metabolic disorders. Here in this review, we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.

Recent Advances in Osteoclast Biological Behavior

With the progress of the aging population, bone-related diseases such as osteoporosis and osteoarthritis have become urgent problems. Recent studies have demonstrated the importance of osteoclasts in bone homeostasis, implying these will be an important mediator in the treatment of bone-related diseases. Up to now, several reviews have been performed on part of osteoclast biological behaviors such as differentiation, function, or apoptosis. However, few reviews have shown the complete osteoclast biology and research advances in recent years. Therefore, in this review, we focus on the origin, differentiation, apoptosis, behavior changes and coupling signals with osteoblasts, providing a simple but comprehensive overview of osteoclasts for subsequent studies.

Citrullinated Histone H3 Mediates Sepsis-Induced Lung Injury Through Activating Caspase-1 Dependent Inflammasome Pathway

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection that often results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). An emerging mechanism of sepsis-induced ARDS involves neutrophils/macrophages undergoing cell death, releasing nuclear histones to cause tissue damage that exacerbates pulmonary injury. While published studies focus on unmodified histones, little is known about the role of citrullinated histone H3 (CitH3) in the pathogenesis of sepsis and ALI. In this study, we found that levels of CitH3 were elevated in the patients with sepsis-induced ARDS and correlated to PaO2/FiO2 in septic patients. Systematic administration of CitH3 peptide in mice provoked Caspase-1 activation in the lung tissue and caused ALI. Neutralization of CitH3 with monoclonal antibody improved survival and attenuated ALI in a mouse sepsis model. Furthermore, we demonstrated that CitH3 induces ALI through activating Caspase-1 dependent inflammasome in bone marrow derived macrophages and bone marrow derived dendritic cells. Our study suggests that CitH3 is an important mediator of inflammation and mortality during sepsis-induced ALI.

HUMAN CAPITAL, WELL-BEING AND GROWTH RATE OF RURAL–URBAN MIGRATION IN CHINA

This study investigates how human capital and well-being have influenced growth rate of rural–urban migration in China. Using rural household and family member data from the China Family Panel Studies database for 2010, 2012, 2014 and 2016, we find that human capital has a significant and positive impact on migrant workers’ well-being. Migrant workers’ human capital and urban well-being positively affect growth rate of rural–urban migration, in which, urban well-being is an important mediator for human capital to play an important role in growth rate of rural–urban migration. Our study indicates that the Chinese government should accelerate implementing policies that increase investment in rural public’s basic education and financial support.

Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2

SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNα) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNα and that both Serpin E1 and nafamostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.

Ivan Turgenev als Netzwerker: Digitale Kuratierung seiner europäischen, insbesondere deutschen literarischen Kontakte (am Beispiel seines Briefwechsels vom Juni 1868 bis Mai 1869)

The Russian writer Ivan Sergeevič Turgenev (1818–83), who lived in Western Europe (Germany, England, and France) during the second half of his life, is considered the most important mediator between Russia and Europe in the nineteenth century due to his wide and intensive contacts in East and West. The paper aims to trace Turgenev’s literary and cultural contacts using the epistemological model of the net and current methods of analyzing social networks on a quantitative and qualitative level. In concrete terms, Turgenev’s postal relations from a single year (from June 1868 to May 1869) are presented and evaluated in tabular form and as GEPHI graphs. Beyond the purely quantitative network visualization and viewing, the attempt is made to provide a cultural weighting of the exchange, especially of Turgenev’s German contacts. The network-specific weighting of these contacts results in a different emphasis than usual in Turgenev research, which focuses on Turgenev’s contacts with important German writers. The qualitative analysis carried out on the basis of the visualization shows that Turgenev’s contacts with literary celebrities such as Theodor Storm, Berthold Auerbach, and Paul Heyse proved to be weak ties. In contrast, his relationship with the little-known literary figure Ludwig Pietsch deserves to be called a strong tie. Turgenev’s position and agency in the network can be described with Burt as a “broker” attitude.

Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth–associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.

Sense of Contribution Mediates Cultural Differences in Support-Seeking

Compared to European Americans, East Asians are more reluctant to seek social support when dealing with stressful events. The purpose of this study is to test three possible explanations of these cultural differences. In addition to examining both harmony seeking and rejection avoidance (two facets of interdependence reflecting relationship concerns) as possible explanations, we propose a novel explanation, namely that sense of contribution (i.e., the degree to which one contributes to other people’s well-being) may be an important mediator for explaining cultural differences in support seeking. A survey was conducted on adults living in Japan and the U.S. Results revealed that Japanese less often rely on social support, and sense of contribution significantly mediates the association between culture and support seeking. In contrast, the mediating role of both harmony seeking and rejection avoidance was not supported. The results indicate that cultural differences in support seeking may be more adequately accounted for by sense of contribution than relationship concerns.

Potential Metabolic Biomarkers in Adult Asthmatics

Asthma is the most common chronic airway inflammation, with multiple phenotypes caused by complicated interactions of genetic, epigenetic, and environmental factors. To date, various determinants have been suggested for asthma pathogenesis by a new technology termed omics, including genomics, transcriptomics, proteomics, and metabolomics. In particular, the systematic analysis of all metabolites in a biological system, such as carbohydrates, amino acids, and lipids, has helped identify a novel pathway related to complex diseases. These metabolites are involved in the regulation of hypermethylation, response to hypoxia, and immune reactions in the pathogenesis of asthma. Among them, lipid metabolism has been suggested to be related to lung dysfunction in mild-to-moderate asthma. Sphingolipid metabolites are an important mediator contributing to airway inflammation in obese asthma and aspirin-exacerbated respiratory disease. Although how these molecular variants impact the disease has not been completely determined, identification of new causative factors may possibly lead to more-personalized and precise pathway-specific approaches for better diagnosis and treatment of asthma. In this review, perspectives of metabolites related to asthma and clinical implications have been highlighted according to various phenotypes.