Macrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis

Macrophages are a rich source of macrophage migration inhibitory factor (MIF). It is well established that macrophages and MIF play a pathogenic role in anti-glomerular basement membrane crescentic glomerulonephritis (anti-GBM CGN). However, whether macrophages mediate anti-GBM CGN via MIF-dependent mechanism remains unexplored, which was investigated in this study by specifically deleting MIF from macrophages in MIFf/f−lysM−cre mice. We found that compared to anti-GBM CGN induced in MIFf/f control mice, conditional ablation of MIF in macrophages significantly suppressed anti-GBM CGN by inhibiting glomerular crescent formation and reducing serum creatinine and proteinuria while improving creatine clearance. Mechanistically, selective MIF depletion in macrophages largely inhibited renal macrophage and T cell recruitment, promoted the polarization of macrophage from M1 towards M2 via the CD74/NF-κB/p38MAPK-dependent mechanism. Unexpectedly, selective depletion of macrophage MIF also significantly promoted Treg while inhibiting Th1 and Th17 immune responses. In summary, MIF produced by macrophages plays a pathogenic role in anti-GBM CGN. Targeting macrophage-derived MIF may represent a novel and promising therapeutic approach for the treatment of immune-mediated kidney diseases

Scientometric trends and knowledge maps of global health systems research

Background: In the last few decades, health systems research (HSR) has garnered much attention with a rapid increase in the related literature. This study aims to review and evaluate the global progress in HSR and assess the current quantitative trends. Methods: Based on data from the Web of Science database, scientometric methods and knowledge visualization techniques were applied to evaluate global scientific production and develop trends of HSR from 1900 to 2012. Results: HSR has increased rapidly over the past 20 years. Currently, there are 28,787 research articles published in 3,674 journals that are listed in 140 Web of Science subject categories. The research in this field has mainly focused on public, environmental and occupational health (6,178, 21.46%), health care sciences and services (5,840, 20.29%), and general and internal medicine (3,783, 13.14%). The top 10 journals had published 2,969 (10.31%) articles and received 5,229 local citations and 40,271 global citations. The top 20 authors together contributed 628 papers, which accounted for a 2.18% share in the cumulative worldwide publications. The most productive author was McKee, from the London School of Hygiene \& Tropical Medicine, with 48 articles. In addition, USA and American institutions ranked the first in health system research productivity, with high citation times, followed by the UK and Canada. Conclusions: HSR is an interdisciplinary area. Organization for Economic Co-operation and Development countries showed they are the leading nations in HSR. Meanwhile, American and Canadian institutions and the World Health Organization play a dominant role in the production, collaboration, and citation of high quality articles. Moreover, health policy and analysis research, health systems and sub-systems research, healthcare and services research, health, epidemiology and economics of communicable and non-communicable diseases, primary care research, health economics and health costs, and pharmacy of hospital have been identified as the mainstream topics in HSR fields. These findings will provide evidence of the current status and trends in HSR all over the world, as well as clues to the impact of this popular topic; thus, helping scientific researchers and policy makers understand the panorama of HSR and predict the dynamic directions of research

Electronic Structures of Graphene Layers on Metal Foil: Effect of Point Defects

Here we report a facile method to generate a high density of point defects in graphene on metal foil and show how the point defects affect the electronic structures of graphene layers. Our scanning tunneling microscopy (STM) measurements, complemented by first principle calculations, reveal that the point defects result in both the intervalley and intravalley scattering of graphene. The Fermi velocity is reduced in the vicinity area of the defect due to the enhanced scattering. Additionally, our analysis further points out that periodic point defects can tailor the electronic properties of graphene by introducing a significant bandgap, which opens an avenue towards all-graphene electronics.Comment: 4 figure

Risk of COVID-19 Transmission Aboard Aircraft: An Epidemiological Analysis Based on the National Health Information Platform.

OBJECTIVES This study aims to investigate the risk of COVID-19 transmission on aircraft. METHODS We obtained data on all international flights to Lanzhou, China, from June 1 to August 1, 2020, through the Gansu Province National Health Information Platform and the official website of the Gansu Provincial Center for Disease Control and Prevention. Statistical analysis was then performed. RESULTS Three international flights arrived in Lanzhou. The flights had a total of 700 passengers, of whom 405 (57.9%) were male and 80 (11.4%) were children below age fourteen. Twenty-seven (3.9%) passengers were confirmed to have COVID-19. Confirmed patients were primarily male (17, 65.4%) with a median age of 27.0 years. The majority of confirmed cases were seated in the middle rows of the economy class, or near public facility areas such as restrooms and galleys. The prevalence of COVID-19 did not differ between passengers sitting on window, aisle or middle seats. Compared with passengers sitting on the same row up to two rows behind a confirmed case, passengers seated in the two rows ahead a confirmed case were at a slightly higher risk of being infected. CONCLUSIONS COVID-19 may be transmitted during a passenger flight, although there is still no direct evidence

Disruption of Smad4 impairs TGF-β/Smad3 and Smad7 transcriptional regulation during renal inflammation and fibrosis in vivo and in vitro

The mechanism by which TGF-β regulates renal inflammation and fibrosis is largely unclear; however, it is well accepted that its biological effects are mediated through Smad2 and Smad3 phosphorylation. Following activation, these Smads form heteromeric complex with Smad4 and translocate into the nucleus to bind and regulate the expression of target genes. Here we studied the roles of Smad4 to regulate TGF-β signaling in a mouse model of unilateral ureteral obstruction using conditional Smad4 knockout mice and in isolated Smad4 mutant macrophages and fibroblasts. Disruption of Smad4 significantly enhanced renal inflammation as evidenced by a greater CD45+ leukocyte and F4/80+ macrophage infiltration and upregulation of IL-1β, TNF-α, MCP-1, and ICAM-1 in the obstructed kidney and in IL-1β-stimulated macrophages. In contrast, deletion of Smad4 inhibited renal fibrosis and TGF-β1-induced collagen I expression by fibroblasts. Further studies showed that the loss of Smad4 repressed Smad7 transcription, leading to a loss of functional protein. This, in turn, inhibited IκBα expression but enhanced NF-κB activation, thereby promoting renal inflammation. Interestingly, deletion of Smad4 influenced Smad3-mediated promoter activities and the binding of Smad3 to the COL1A2 promoter, but not Smad3 phosphorylation and nuclear translocation, thereby inhibiting the fibrotic response. Thus, Smad4 may be a key regulator for the diverse roles of TGF-β1 in inflammation and fibrogenesis by interacting with Smad7 and Smad3 to influence their transcriptional activities in renal inflammation and fibrosis

Extracellular Vesicles: Opportunities and Challenges for the Treatment of Renal Diseases

Extracellular vesicles (EVs) are lipid-based membrane-bound particles secreted by virtually all types of cells under both physiological and pathological conditions. Given their unique biological and pharmacological properties, EVs have spurred a renewed interest in their utility for therapeutics. Herein, efforts are made to give a comprehensive overview on the recent advances of EV-based therapy in renal diseases. The fact that EVs are implicated in various renal diseases provides us with new therapeutic modalities by eliminating these pathogenic entities. Strategies that target EVs to inhibit their production, release, and uptake will be discussed. Further, EVs-derived predominantly from stem cells can stimulate tissue repair and ameliorate renal injury via transferring proteins and nucleic acids to injured cells. Such EVs can be exploited as agents in renal regenerative medicine. Finally, we will focus on the specific application of EVs as a novel drug delivery system and highlight the challenges of EVs-based therapies for renal diseases

Nanoscale Surface Redox Chemistry Triggered by Plasmon-Generated Hot Carriers.

Direct photoexcitation of charges at a plasmonic metal hotspot produces energetic carriers that are capable of performing photocatalysis in the visible spectrum. However, the mechanisms of generation and transport of hot carriers are still not fully understood and under intense investigation because of their potential technological importance. Here, spectroscopic evidence proves that the reduction of dye molecules tethered to a Au(111) surface can be triggered by plasmonic carriers via a tunneling mechanism, which results in anomalous Raman intensity fluctuations. Tip-enhanced Raman spectroscopy (TERS) helps to correlate Raman intensity fluctuations with temperature and with properties of the molecular spacer. In combination with electrochemical surface-enhanced Raman spectroscopy, TERS results show that plasmon-induced energetic carriers can directly tunnel to the dye through the spacer. This organic spacer chemically isolates the adsorbate from the metal but does not block photo-induced redox reactions, which offers new possibilities for optimizing plasmon-induced photocatalytic systems