No abstract

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P \ 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the Hao Zhou, Xiu Xu, Weili Yan contributed equally.Members of the LATENT-NHC Study Team are listed in the Supplementary Materials.

Necroptosis is a type of programmed cell death with necrotic morphology, occurring in a variety of biological processes, including inflammation, immune response, embryonic development and metabolic abnormalities. The current nomenclature defines necroptosis as cell death mediated by signal transduction from receptor-interacting serine/threonine kinase (RIP) 1 to RIP3 (hereafter called RIP1/RIP3). However, RIP3-dependent cell death would be a more precise definition of necroptosis. RIP3 is indispensable for necroptosis, while RIP1 is not consistently involved in the signal transduction. Notably, deletion of RIP1 even promotes RIP3-mediated necroptosis under certain conditions. Necroptosis was previously thought as an alternate process of cell death in case of apoptosis inhibition. Currently, necroptosis is recognized to serve a pivotal role in regulating various physiological processes. Of note, it mediates a variety of human diseases, such as ischemic brain injury, immune system disorders and cancer. Targeting and inhibiting necroptosis, therefore, has the potential to be used for therapeutic purposes. To date, research has elucidated the suppression of RIP1/RIP3 via effective inhibitors and highlighted their potential application in disease therapy. The present review focused on the molecular mechanisms of RIP1/RIP3-mediated necroptosis, explored the functions of RIP1/RIP3 in necroptosis, discussed their potential as a novel therapeutic target for disease therapy, and provided valuable suggestions for further study in this field.

Background: Old World non-human primates (OWNHPs) are used for preclinical pigto-NHP studies. However, like pigs, OWNHPs express Neu5Gc, and therefore do not develop natural anti-Neu5Gc antibodies. New World NHPs (NWNHPs) have been reported not to express Neu5Gc. We investigated the potential of NWNHPs in xenotransplantation research. Methods:We investigated expression of Gal, Neu5Gc, and Sd a antigens on RBCs and PBMCs from humans, selected OWNHPs, and capuchin monkeys (a NWNHP). Serum anti-Gal and anti-Neu5Gc IgM and IgG levels were measured by ELISA. Binding of primate serum IgM and IgG to pig RBCs was measured by flow cytometry.

BackgroundA deviant motor behaviour at age 3 to 5 months is predictive of cerebral palsy (CP). Particular features of the early motor repertoire even proved predictive of the degree of functional limitations as classified on the Gross Motor Function Classification System (GMFCS) in children with CP, born preterm.AimsWe aimed to determine whether an association between the early motor repertoire and the GMFCS also holds true for children born at term.Study designLongitudinal study.Subjects79 infants (60 boys and 19 girls; 47 infants born at term; video recorded for the assessment of movements and posture at age 9 to 20 weeks postterm age) who developed CP.Outcome measuresThe GMFCS was applied at age 2 to 5 years.ResultsMotor optimality at age 3 to 5 months showed a significant correlation with functional mobility and activity limitation as classified on the GMFCS at age 2 to 5 years in both children born at term (Spearman rho = − 0.66, p < 0.001) and born preterm (rho = − 0.37, p < 0.05). Infants born preterm were more likely to show normal movement patterns than infants born at term. A normal posture and an abnormal, jerky (yet not monotonous) movement character resulted in better levels of function and mobility. With the exception of one, none of the infants showed fidgety movements. A cramped-synchronised movement character, repetitive opening and closing of the mouth, and abnormal finger postures characterised children who would show a poor self-mobility later.ConclusionsAssessing the quality of motor performance at 9 to 20 weeks postterm age (irrespective of the gestational age) improves our ability to predict later functional limitations in children with CP.

The α-Gal epitope (Galα1,3Galα1,4GlcNAc-R) is ubiquitously presented in non-primate mammals, marsupials and New World Monkeys, but it is absent in humans, apes and Old World monkeys. However, the anti-Gal antibody (~1% of immunoglobulins) is naturally generated in human, and is found as the immunoglobulin G (IgG), IgM and IgA isotypes. Owing to the specific binding of the anti-Gal antibody with the α-Gal epitope, humans have a distinct anti-α-gal reactivity, which is responsible for hyperacute rejection of organs transplanted from α-gal donors. In addition, the α1,3 galactosyltransferases (α1,3GT) can catalyze the synthesis of the α-Gal epitope. Therefore, the α1,3GT gene, which encodes the α1,3GT, is developed profoundly. The distributions of the α-Gal epitope and anti-Gal antibody, and the activation of α1,3GT, reveal that the enzyme of α1,3GT in ancestral primates is ineffective. Comparison of the nucleotide sequence of the human α1,3-GT pseudogene to the corresponding different species sequence, and according to the evolutionary tree of different species, the results of evolutionary inactivation of the α1,3GT gene in ancestral primates attribute to the mutations under a stronger selective pressure. However, on the basis of the structure, the mechanism and the specificity of the α-Gal epitope and anti-Gal antibody, they can be applied to clinical exploitation. Knocking out the α1,3GT gene will eliminate the xenoantigen, Gal(α1,3)Gal, so that the transplantation of α1,3GT gene knockout pig organ into human becomes a potential clinically acceptable treatment for solving the problem of organ shortage. By contrast, the α-Gal epitope expressed through the application of chemical, biochemical and genetic engineering can be exploited for the clinical use. Targeting anti-Gal-mediated autologous tumor vaccines, which express α-Gal epitope to antigen-presenting cells, would increase their immunogenicity and elicit an immune response, which will be potent enough to eradicate the residual tumor cells. For tumor vaccines, the way of increasing immunogenicity of certain viral vaccines, including flu vaccines and human immunodeficiency virus vaccines, can also be used in the elderly. Recently, α-Gal epitope nanoparticles have been applied to accelerate wound healing and further directions on regeneration of internally injured tissues.

The DDE model successfully described the non-linear pharmacokinetics of VPA. Furthermore, the proposed population pharmacokinetic model of VPA can be used to design rational dosage regimens to achieve desirable serum concentrations.

These data show impairment of allogeneic T cell and B cell function in mice with defective complement activation and suggest a predominant role for the classical pathway in stimulating alloimmunity. The terminal pathway seems unimportant in this regard. This extends the results reported for soluble protein antigens and demonstrates a surprisingly marked effect on the alloresponse despite the presence of a stringent antigenic stimulus. These results have implications for the prevention of sensitization in naïve transplant recipients.