The history of thrombotic thrombocytopenic purpura research: a narrative review.

BACKGROUND AND OBJECTIVE Thrombotic thrombocytopenic purpura (TTP) is a rare but debilitating thrombotic microangiopathy that results from severe deficiency of the enzyme ADAMTS13. The disorder was first described in the early 20th century, but the pathophysiology of the disease has only been elucidated in the past three decades. In this narrative review, we will summarize the milestone moments in the history of TTP research and discovery. METHODS We searched literature using PubMed from 1924 to 2023 using the following free text searches: "thrombotic thrombocytopenic purpura", "Moschcowitz disease", and "thrombotic microangiopathy". We found 6,917 peer-reviewed articles and sorted through these for relevant literature pertinent to the review. A total of 46 articles were included for review and the remainder were excluded. KEY CONTENT AND FINDINGS The history of TTP research was reviewed, with a sampling of major events in the evolution of the understanding of the pathophysiology and treatment of the disease discussed here. There remains much to be learned about the nature of the disease in order to develop more specific and less harmful treatments. CONCLUSIONS An overview of the major discoveries that have led to our current understanding of TTP reveals the results of collaboration of multiple groups of physicians and scientists through the past century, with additional breakthroughs likely to occur in the future because of that same collaborative spirit

Effect of policy incentives on the uptake of electric vehicles in China

© 2019 by the authors. In the backdrop of growing public concerns about climate change and air pollution, and the contribution of petroleum combustion in the transport sector to these issues, China has introduced a range of policy incentives for promoting the uptake of electric vehicles (EVs). These incentives have resulted in a rapid increase in EV stocks since the early 2010s, and this trend is expected to continue, or even accelerate, in the years to come, which would, in turn, lead to a policy-oriented EV market. The primary objective of the project is to develop an understanding of the effect of various policy incentives on EV uptake based on annual data of 43 cities from 2011 to 2017, and these policies mainly refer to those that focus on EV purchasing, registering, driving, and charging stages. The novelty of this paper is that we focused on policy effect on EV adoption behavior, rather than adoption intention which has widely been analyzed in previous studies. Results showed that the abolishment of purchasing and driving restriction, government subsidies, purchase tax exemption, and dedicated license plates significantly promote EV diffusion, and the effect of the two restrictions are more powerful. Thus, this study suggested that abolishment of purchasing and driving restrictions can be insisted to drive EV market share, meanwhile improving policies that can guide consumers through various motivations are also necessary

How epidemic information and policy information impact anti-infection behaviors: a cross-cultural study under social influence framing

Three preregistered experiments examined to what extent information about an epidemic situation provided by experts and information about anti-infection policies promoted by governments/media influenced anti-infection behaviors. The above effects were examined among populations from different countries (in Experiments 2 and 3) and across self-construals (in Experiment 3). In three experiments, participants (N =706) were presented with a scenario where experts provided (or did not provide) information about an epidemic situation and governments/media promoted (or did not promote) information about anti-infection policies. After that, participants indicated their willingness to adopt anti-infection behaviors. Results across three experiments showed that both types of information independently increased participants’ anti-infection behaviors. In Experiments 2 and 3, we further found that the epidemic information had a larger impact on inducing anti-infection behaviors than the policy information, which was robust and consistent across countries and self-construals. Findings were discussed under the framework of social influence and in terms of practical implications for pandemic situations like the COVID-19.Social decision makin

Emerging and reemerging helminthiases and the public health of China.

Despite great strides in their control throughout the People's Republic of China, helminth infections remain an important public health problem. The Institute of Parasitic Diseases of the Chinese Academy of Preventive Medicine, under the guidance of the Chinese Ministry of Health, completed a nationwide survey of more than 1 million people that showed the high prevalence and intensity of intestinal nematode infections; prevalence can sometimes exceed 50% in the Yangtze River valley provinces. Schistosoma japonicum is also a major cause of illness in this region. Attempts to control Chinese helminthic diseases with conventional anthelminthic drugs have been partially thwarted by high posttreatment rates of reinfection. Recently, several new human trematode pathogens have been identified. Novel approaches to chemoprophylaxis and vaccination may alleviate the public health problem caused by Chinese helminths. However, recombinant helminth vaccine development will depend on first cataloguing the extensive genetic diversity of Chinese helminths and candidate vaccine antigens. Evidence from biogeography, genetics, and systematics suggests that the genetic diversification of Chinese helminths and their vectors is an ongoing evolutionary process that began 12 million years ago near the convergence of major Asian river systems. Construction of the Three Gorges Super Dam on the Yangtze River may promote the emergence and reemergence of new helminths and their snail vector

Histone-induced thrombotic thrombocytopenic purpura in adamts13−/− zebrafish depends on von Willebrand factor

Thrombotic thrombocytopenic purpura (TTP) is caused by severe deficiency of ADAMTS13 (A13), a plasma metalloprotease that cleaves endothelium-derived von Willebrand factor (VWF). However, severe A13 deficiency alone is often not sufficient to cause an acute TTP; additional factors may be required to trigger the disease. Using CRISPR/Cas9, we created and characterized several novel zebrafish lines carrying a null mutation in a13−/−, vwf, and both. We further used these zebrafish lines to test the hypothesis that inflammation that results in neutrophil activation and release of histone/DNA complexes may trigger TTP. As shown, a13−/− zebrafish exhibit increased levels of plasma VWF antigen, multimer size, and ability of thrombocytes to adhere to a fibrillar collagen-coated surface under flow. The a13−/−zebrafish also show an increased rate of occlusive thrombus formation in the caudal venules after FeCl3 injury. More interestingly, a13−/− zebrafish exhibit ~30% reduction in the number of total, immature, and mature thrombocytes with increased fragmentation of erythrocytes. Administration of a lysine-rich histone results in more severe and persistent thrombocytopenia and a significantly increased mortality rate in a13−/−zebrafish than in wildtype (wt) ones. However, both spontaneous and histone-induced TTP in a13−/− zebrafish are rescued by the deletion of vwf. These results demonstrate a potentially mechanistic link between inflammation and the onset of TTP in light of severe A13 deficiency; the novel zebrafish models of TTP may help accelerate our understanding of pathogenic mechanisms and the discoveries of novel therapeutics for TTP and perhaps other arterial thrombotic disorders

Bioinspired materials for underwater adhesion with pathways to switchability

Strong adherence to underwater or wet surfaces for applications like tissue adhesion and underwater robotics is a significant challenge. This is especially apparent when switchable adhesion is required that demands rapid attachment, high adhesive capacity, and easy release. Nature displays a spectrum of permanent to reversible attachment from organisms ranging from the mussel to the octopus, providing inspiration for underwater adhesion design that has yet to be fully leveraged in synthetic systems. Here, we review the challenges and opportunities for creating underwater adhesives with a pathway to switchability. We discuss key material, geometric, modeling, and design tools necessary to achieve underwater adhesion similar to the adhesion control demonstrated in nature. Through these interdisciplinary efforts, we envision that bioinspired adhesives can rise to or even surpass the extraordinary capabilities found in biological systems

Optical study on doped polyaniline composite films

Localization driven by disorder has a strong influence on the conducting property of conducting polymer. A class of authors hold the opinion that disorder in the material is homogeneous and conducting polymer is disordered metal close to Anderson-Mott Metal-Insulator transition, while others treat the disorder as inhomogeneous and have the conclusion that conducting polymer is a composite of ordered metallic regions and disordered insulating regions. The morphology of conducting polymers is an important factor that have influence on the type and extent of disorder. Different protonic acids used as dopants and moisture have affection on polymer chain arrangement and interchain interactions. A PANI-CSA film, two PANI-CSA/PANI-DBSA composite films with different dopants ratio, and one of the composite films with different moisture content are studied. Absolute reflectivity measurements are performed on the films. Optical conductivity and the real part of dielectric function are calculated by Kramers-Kronig(KK) relations. $\sigma_1(\omega)$ and $\epsilon_1(\omega)$ derivate from simple Drude model in low frequency range and tendencies of the three sample are different and non-monotonic. The Localization Modified Drude model(LMD) in the framework of Anderson-Mott theory can not give a good fit to the experimental data. By introducing a distribution of relaxation time into LMD, reasonable fits for all three samples are obtained. This result supports the inhomogeneous picture.Comment: 6 figures, 7 page

Identification and Initial Functional Characterization of a Human Vascular Cell-Enriched Long Noncoding RNA

OBJECTIVE: Long noncoding RNAs (lncRNAs) represent a rapidly growing class of RNA genes with functions related primarily to transcriptional and post-transcriptional control of gene expression. There is a paucity of information about lncRNA expression and function in human vascular cells. Thus, we set out to identify novel lncRNA genes in human vascular smooth muscle cells and to gain insight into their role in the control of smooth muscle cell phenotypes. APPROACH AND RESULTS: RNA sequencing of human coronary artery smooth muscle cells revealed 31 unannotated lncRNAs, including a vascular cell-enriched lncRNA (smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA [SENCR]). Strand-specific reverse transcription polymerase chain reaction (PCR) and rapid amplification of cDNA ends indicate that SENCR is transcribed antisense from the 5' end of the FLI1 gene and exists as 2 splice variants. RNA fluorescence in situ hybridization and biochemical fractionation studies demonstrate SENCR is a cytoplasmic lncRNA. Consistent with this observation, knockdown studies reveal little to no cis-acting effect of SENCR on FLI1 or neighboring gene expression. RNA-sequencing experiments in smooth muscle cells after SENCR knockdown disclose decreased expression of Myocardin and numerous smooth muscle contractile genes, whereas several promigratory genes are increased. Reverse transcription PCR and Western blotting experiments validate several differentially expressed genes after SENCR knockdown. Loss-of-function studies in scratch wound and Boyden chamber assays support SENCR as an inhibitor of smooth muscle cell migration. CONCLUSIONS: SENCR is a new vascular cell-enriched, cytoplasmic lncRNA that seems to stabilize the smooth muscle cell contractile phenotype