No abstract

S. 2019. "A comprehensive genome variation map of melon identifies multiple domestication events and loci influencing agronomic traits". Nature Genetics.

Background: Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. Methods: A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children’s Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. Results: Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. Conclusions: More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.

Background The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19. Methods We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children's Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed. Results The mean age of the infected infants was 6.43 months, with a range of 2-12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.

Heterogeneous nuclear ribonucleoparticule A1/A2 (hnRNP A1/A2) and splicing factor 2/alternative splicing factor (SF2/ASF) are pivotal for precursor messenger RNA (pre-mRNA) splicing. Interferon regulatory factor-3 (IRF-3) plays critical roles in host defense against viral and microbial infection. Truncated IRF-3 proteins resulting from alternative splicing have been identified and characterized as functional antagonists to full-length IRF-3. In this study, we examined the molecular mechanism for splicing regulation of IRF-3 pre-mRNA and first reported the regulatory effect of hnRNP A1/A2 and SF2/ASF on IRF-3 splicing and activation. RNA interference-mediated depletion of hnRNP A1/A2 or SF2/ASF in human non-small cell lung cancer (NSCLC) cells increased exclusion of exons 2 and 3 of IRF-3 gene and reduced expression levels of IRF-3 protein and IRF-3 downstream effector molecules interferon-beta and CXCL10/IP-10. In addition, direct binding of hnRNP A1 and SF2/ASF to specific binding motifs in IRF-3 intron 1 was confirmed by RNA electrophoretic mobility shift assay. Subsequent minigene splicing assay showed that IRF-3 minigenes with mutated hnRNPA 1/A2 or SF2/ASF binding motifs increased exclusion of exons 2 and 3. Moreover, knockdown of hnRNP A1/A2 or SF2/ASF in NSCLC cells reinforced phytohemagglutinin-induced tumor necrosis factor-alpha release by peripheral blood mononuclear cells (PBMC) but suppressed that of interleukin-10 in NSCLC/PBMC co-cultures. Taken together, our results suggest that specific knockdown for hnRNP A1/A2 or SF2/ASF increase exclusion of exons 2 and 3 of IRF-3 pre-mRNA and influence immunomodulatory functions of human NSCLC cells.

RNA sequencing has been extensively used to study specific gene expression patterns to discover potential key genes related to complex traits of interest in animals. Of note, a new regulatory mechanism builds a large-scale regulatory network among transcriptome, where lncRNAs act as competing endogenous RNAs (ceRNAs) to sponge miRNAs to regulate the expression of miRNA target genes post-transcriptionally. In this study, we sequenced the cDNA and sRNA libraries of nine liver samples from three Holstein cows during dry period, early lactation, and peak of lactation with HiSeq platform. As a result, we identified 665 genes, 57 miRNAs and 33 lncRNAs that displayed differential expression patterns across periods. Subsequently, a total of 41ceRNA pairs (lncRNA-mRNA) sharing 11 miRNAs were constructed including 30 differentially expressed genes. Importantly, 12 among them were presented in our large metabolic networks, and predicted to influence the lipid metabolism through insulin, PI3K-Akt, MAPK, AMPK, mTOR, and PPAR signaling pathways, thus, these genes were considered as the most promising candidates for milk fat formation. To our knowledge, this is first investigation to profile the ceRNA regulatory networks of liver transcriptome that could affect milk fat synthesis in bovine, providing a new view of the regulatory mechanism of RNAs.

Tic disorders (TD) are a group neuropsychiatric disorders with childhood onset characterized by tics, i.e. repetitive, sudden, and involuntary movements or vocalizations; and Tourette syndrome (TS) is the most severe form of TD. Their clinical manifestations are diverse; and are often associated with various psychopathological and/ or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders. Individual severity and response to treatment are highly variable, and there are some refractory cases, which are less responsive to conventional TD treatment. TD/TS are also common in the Chinese pediatric population. To help improve the understanding of TD for pediatricians and other health professionals, and to improve its diagnosis and treatment in China, the Chinese Child Neurology Society (CCNS) has developed an Expert Consensus on Diagnosis and Treatment of TD in China, which is based on our clinical experience and the availability therapeutic avenues. It is focused on clinical diagnosis and evaluation of TD and its comorbidities, psychological and educational intervention, nonpharmacological therapy, pharmacological treatment, including traditional Chinese medicine and acupuncture, as well as prognosis in children with TD in China. A summary of the current status of TD and up-to-date diagnosis and treatment recommendations for TD in China is presented here.

Our previous linkage study demonstrated that the 9q22-q23 chromosome region showed a 'suggestive' linkage to nicotine dependence (ND) in the Framingham Heart Study population. In this study, we provide further evidence for the linkage of this region to ND in an independent sample. Within this region, the gene encoding Src homology 2 domain-containing transforming protein C3 (SHC3) represents a plausible candidate for association with ND, assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerströ m Test for ND (FTND). We utilized 11 single-nucleotide polymorphisms within SHC3 to examine the association with ND in 602 nuclear families of either African-American (AA) or EuropeanAmerican (EA) origin. Individual SNP-based analysis indicated three SNPs for AAs and one for EAs were significantly associated with at least one ND measure. Haplotype analysis revealed that the haplotypes A-C-T-A-T-A of rs12519-rs3750399-rs4877042-rs2297313-rs1547696-rs1331188, with a frequency of 27.8 and 17.6%, and C-T-A-G-T of rs3750399-rs4877042-rs2297313-rs3818668-rs1547696, at a frequency of 44.7 and 30.6% in the AA and Combined samples, respectively, were significantly inversely associated with the ND measures. In the EA sample, another haplotype with a frequency of 10.6%, A-G-T-G of rs1331188-rs1556384-rs4534195-rs1411836, showed a significant inverse association with ND measures. These associations remained significant after Bonferroni correction. We further demonstrated the SHC3 contributed 40.1-59.2% (depending on the ND measures) of the linkage signals detected on chromosome 9. As further support, we found that nicotine administered through infusion increased the Shc3 mRNA level by 60% in the rat striatum, and decreased it by 22% in the nucleus accumbens (NA). At the protein level, Shc3 was decreased by 38.0% in the NA and showed no change in the striatum. Together, these findings strongly implicate SHC3 in the etiology of ND, which represents an important biological candidate for further investigation.