Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).
Two series of peptides that specifically bind to the extracellular domain of the ␣ chain of the human interleukin-5 receptor (IL-5R␣), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor ␣͞ heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor ␣ chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5R␣ extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R ␣ chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors.I nterleukin-5 (IL-5) is a T cell-derived hematopoietic cytokine that acts exclusively on cells of the eosinophil and basophil lineage (1, 2). Although IL-5 can regulate many of the functions of mature, terminally differentiated eosinophils such as cell survival (3), adhesion (4), and activation (5), its primary function is to promote the differentiation and expansion of eosinophil precursors in the bone marrow (6).Transgenic mice that constitutively overexpress IL-5 in their lungs exhibit systemic and airway eosinophilia, bronchial hyperreactivity, and histopathological features characteristic of human asthma (7). Administration of recombinant IL-5 into the airways of either guinea pigs (8) or mildly asthmatic individuals (9) promotes a lung eosinophilia and bronchial hyperreactivity. Moreover, blocking the activity of IL-5 through administration of neutralizing anti-IL-5 antibodies (10-12), or through IL-5 gene deletion (13), prevents allergen-induced airway eosinophilia and bronchial hyperreactivity. Together, these data demonstrate that IL-5 plays a central role in the development of allergen-induced eosinophilia in animals and suggest that an anti-IL-5 therapeutic could provide an alternative approach to the treatment of human asthma perhaps more specific than current anti-inf lammatory therapies such as inhaled corticosteroids.The IL-5 receptor is a heterodimer consisting of an ␣ chain that specifically binds IL-5 and a signal-transducing  c chain shared with the receptors for two structurally related cytokines: granulocyte-macrophage colony-stimulating factor (GM-CSF) and . A number of protein-based IL-5 antagonists have been reported, including soluble IL-5 receptor ␣ chains (IL5R␣s) that sequester the ligand in solution (15), single point mutants of IL...
The fruits of China's rapid economic development over the 3 decades have not been distributed fairly across different regions. Using data from a sample of 815 Chinese listed firms during 1998-2004, our error-correction investment model showes evidence of different financial constraints on firms' investment in different regions. We argue that China's regional development policies have contributed greatly to the regional inequalities. To control the rising inequality, China has shifted its focus from the coast to the interior regions. However, it is becoming increasingly difficult for the government to direct the economy, as market mechanisms now have a far greater influence on the economy than the government does. The people-centered approach of the current leadership has meant that substantial attention has been placed on regional development disparities in an attempt to build a "harmonious society." China needs further extensive reforms if all the measures for reducing regional disparity are to be effective. Copyright (c) 2008 The Authors Journal compilation (c) 2008 Institute of World Economics and Politics, Chinese Academy of Social Sciences.
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