Metabolomics and transcriptomics unravel the mechanism of browning resistance in Agaricus bisporus.

Agaricus bisporus is widely consumed on the world market. The easy browning of mushroom surface is one of the most intuitive factors affecting consumer purchase. A certain cognition on browning mechanism has been made after years of research. At present, people slow down the browning of mushrooms mainly by improving preservation methods. In addition, breeding is also a reliable way. In the production practice, we have identified some browning-resistant varieties, and we selected a browning-resistant variety to compare with an ordinary variety to reveal the resistance mechanism. Using transcriptomics and metabolomics, the differences in gene expression and metabolite levels were revealed, respectively. The results showed that differentially expressed genes (DEGs) like AbPPO4, AbPPO3 and AbPPO2 were differently expressed and these DEGs were involved in many pathways related to browning. The expression of AbPPO expression play an important role in the browning of A. bisporus and multiple PPO family members are involved in the regulation of browning. However, the resistance to browning cannot be judged only by the expression level of AbPPOs. For metabolomics, most of the different metabolites were organic acids. These organic acids had a higher level in anti-browning (BT) than easy-browning varieties (BS), although the profile was very heterogeneous. On the contrary, the content of trehalose in BS was significantly higher than that in BT. Higher organic acids decreased pH and further inhibited PPO activity. In addition, the BS had a higher content of trehalose, which might play roles in maintaining PPO activity. The difference of browning resistance between BS and BT is mainly due to the differential regulation mechanism of PPO.

[A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China].

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS: Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.

Genome Survey and Transcriptome Analysis on Mycelia and Primordia of Agaricus blazei.

Agaricus blazei, a type of edible straw-rotting mushroom with somewhat sweet taste and fragrance of almonds, has attracted considerable scientific and practical attention. High-throughput Illumina PE150 and PacBio RSII platform were employed to generate a genomic sequence. De novo assembly generated 36 contigs with 38,686,133 bp in size, containing 10,119 putative predicted genes. Additionally, we also studied transcriptional regulation of the mycelia and the primordia for exploration of genes involved in fruiting body formation. Expression profiling analysis revealed that 2,164 genes were upregulated in mycelia and 1,557 in primordia. Functional enrichment showed that differentially expressed genes associated with response to stress, ribosome biogenesis, arginine biosynthesis, and steroid biosynthesis pathway were more active in fruiting body. The genome and transcriptome analysis of A. blazei provide valuable sequence resources and contribute to our understanding of genes related to the biosynthesis pathway of polysaccharide and benzaldehyde, as well as the fruiting body formation.

Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in Patients with Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Orthotopic liver transplantation (OLT) improves the prognosis of patients with hepatocellular carcinoma (HCC). Moreover, the complement system is a powerful immune effector that can affect liver function and process of liver cirrhosis. However, studies correlating the complement system with tacrolimus metabolism after OLT are scarce. In this study, the role of single nucleotide polymorphisms (SNPs) associated with the sixth complement component (C6) in tacrolimus metabolism was investigated during the early stages of liver transplantation. METHODS: The study enrolled 135 adult patients treated with OLT for HCC between August 2011 and October 2013. Ten SNPs in C6 gene and rs776746 in cytochrome P450 3A5 (CYP3A5) gene were investigated. The tacrolimus levels were monitored daily during 4 weeks after transplantation. RESULTS: Both donor and recipient CYP3A5 rs776746 allele A were correlated with decreased concentration/dose (C/D) ratios. Recipient C6 rs9200 allele G and donor C6 rs10052999 homozygotes were correlated with lower C/D ratios. Recipient CYP3A5 rs776746 allele A (yielded median tacrolimus C/D ratios of 225.90 at week 1 and 123.61 at week 2), C6 rs9200 allele G (exhibited median tacrolimus C/D ratios of 211.31 at week 1, 110.23 at week 2, and 99.88 at week 3), and donor CYP3A5 rs776746 allele A (exhibited median C/D ratios of 210.82 at week 1, 111.06 at week 2, 77.49 at week 3, and 85.60 at week 4) and C6 rs10052999 homozygote (exhibited median C/D ratios of 167.59 at week 2, 157.99 at week 3, and 155.36 at week 4) were associated with rapid tacrolimus metabolism. With increasing number of these alleles, patients were found to have lower tacrolimus C/D ratios at various time points during the 4 weeks after transplantation. In multiple linear regression analysis, recipient C6 rs9200 group (AA vs. GG/GA) was found to be related to tacrolimus metabolism at weeks 1, 2, and 3 (P = 0.005, P = 0.045, and P = 0.033, respectively), whereas donor C6 rs10052999 group (CC/TT vs. TC) was demonstrated to be correlated with tacrolimus metabolism only at week 4 (P = 0.001). CONCLUSIONS: Recipient C6 gene rs9200 polymorphism and donor C6 gene rs10052999 polymorphism are new genetic loci that affect tacrolimus metabolism in patients with HCC after OLT.

[Efficacy of low-dose interferon therapy for treating chronic hepatitis C patients who cannot tolerate standard treatment].

OBJECTIVE: To investigate the therapeutic efficacy of interferon (IFN) therapy and risk of long-term administration for chronic hepatitis C (CHC) patients who cannot tolerate the standard treatment. METHODS: Forty-six CHC patients who had proven intolerant to standard treatments were treated with low-dose IFN (non-pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin (RBV; 0.6g to 0.9 g/d) for 72 weeks. RESULTS: Forty-three (93.5%) of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects (low white blood cell and platelet counts) that required treatment withdrawal. The virology response rates over treatment time were: rapid virologic response (RVR): 10.9%; early virus response (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response: 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who achieved RVR, EVR, or 24 weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis. CONCLUSIONS: Our study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerant to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.