Biology subjects

Mei, J.

Publications and source records attributed to Mei, J..

22 records · Page 2Linked to original sources

bioRxiv2020

Characterization of clinical significance of PD-1/PD-Ls expression and methylation in patients with low grade glioma

BackgroundImmune checkpoints play crucial roles in immune escape of cancer cells. However, the exact prognostic values of expression and methylation of programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1) and PD-L2 in low-grade glioma (LGG) have not been defined yet. MethodsA total of 514 LGG samples from TCGA dataset containing both PD-1, PD-L1 and PD-L2 expression, DNA methylation, and survival data were enrolled into our study. The clinical significance of PD-1/PD-Ls expression and methylation in LGG were explored. Besides, the correlation between PD-1/PD-Ls expression and methylation with the infiltration levels of tumor-infiltrating immune cells (TIICs) was assessed. Moreover, GO enticement analysis of PD-1/PD-Ls co-expressed genes was performed as well. R 3.6.2 and GraphPad Prism 8 were applied as main tools for the statistical analysis and graphical exhibition. ResultsPD-1/PD-Ls had distinct co-expression patterns in LGG tissues. The expression and methylation status of PD-1/PD-Ls seemed to be various in different LGG subtypes. Besides, upregulated PD-1/PD-Ls expression and hypo-methylation of PD-1/PD-Ls were associated with worse survival in LGG patients. In addition, PD-1/PD-Ls expression was revealed to be positively associated with TIICs infiltration, while their methylation was negatively associated with TIICs infiltration. Moreover, the PD-1/PDLs correlated gene profiles screening and Gene Ontology (GO) enrichment analysis uncovered that PD-1/PDLs and their positively correlated gene mainly participated in immune response related biological processes. ConclusionsHigh expression and hypo-methylation of PD-1/PD-Ls significantly correlated with unfavorable survival in LGG patients, suggesting LGG patients may benefit from PD1/PD-Ls checkpoint inhibitors treatment.

bioinformatics↗

bioRxiv2020

Sclerotinia sclerotiorum hijacks copper from its host for infection

Sclerotinia sclerotiorum induces host reactive oxygen species (ROS) production, which leads to necrosis in the host, allowing the pathogen to absorb nutrients from the dead tissues. Here, we found that three S. sclerotiorum genes involved in copper ion import/transport, SsCTR1, SsCCS and SsATX1, were significantly up-regulated during infection of Brassica oleracea. Function analysis revealed that these genes involved in fungal ROS detoxification, oxalic acid production, pathogen establishment and virulence. On the host side, four genes putatively involved in copper ion homeostasis, BolCCS, BolCCH, BolMT2A and BolDRT112, were significantly down-regulated in susceptible B. oleracea, but stably expressed in resistant B. oleracea during infection. Their homologs were found to promote resistance to necrotrophic pathogens and increase antioxidant activity in Arabidopsis thaliana. Furthermore, copper concentration analysis indicated that copper is transported into the necrotic area from healthy area during infection. Collectively, our data suggest that S. sclerotiorum hijacks host copper to detoxify ROS, whereas the resistant hosts restrict the supply of essential copper nutrients to S. sclerotiorum by maintaining copper ion homeostasis during infection.

pathology↗

bioRxiv2019

Autophagy-related genes atg7 and beclin1 are essential for energy metabolism and survival during the larval-to-juvenile transition stage of zebrafish

High mortality is usually observed during the transition from larvae to juvenile in teleost which is related to the transition from endogenous to exogenous feeding. Autophagy is an evolutionary regulated cellular mechanism highly conserved in eukaryotic organisms to maintain energy homeostasis against stress including starvation. To investigate whether autophagy plays a role during the larval-juvenile transition, we generated atg7 and beclin1 zebrafish mutant lines using CRISPR/Cas9 technology. In this study, both atg7 and beclin1 null zebrafish exhibited a normal body confirmation; nevertheless, they completely died around 15 dpf and 9 dpf respectively. During larval-juvenile transition period, atg7 and beclin1 mutants were unable to cope with the metabolic stress after yolk absorption at 5 dpf and fail to activate autophagy in response to nutrient restriction, and without external feeding, all mutants died nearly at 8 dpf. Dramatic defects in the intestine architecture and metabolic functions in the liver were observed even though providing larvae with an external food supply, suggesting that autophagy isnt only important during yolk depletion but also within food plenty. Treatment with rapamycin, an activator of autophagy, could effectively extend the survival time of both atg7 and beclin1 null zebrafish through lowering the metabolic rate while it couldnt activate autophagy in mutants via the canonical pathway. Our findings provided a molecular evidence for the physiological, histological and metabolic changes that occur during the transition process from the larval to the juvenile stages and the chief role of autophagy on the body metabolism during these turning milestones.\n\nAuthor summaryZebrafish Danio rerio has emergrd one of the most powerful research models for studying genes expression during early embryogenesis and postnatal development. On the basis of the cell mechanisms, Macroautphagy, a natural regulated pathway disassembles unnecessary or dysfunctional components orchestrated by more than 36 autophagy related-genes conserved from yeast to mammals. Among those genes are atg7 and beclin1 which have been proved to play an important role in regulating post natal development in some mammals however their roles during zebrafish development still unedited. During this research, CRISPER/CAS9 were adopted to know atg7 and beclin1 knockout effects on the mutants metabolism during shifting from maternal yolk acquisition to exogenous feeding and the role of autophagy during the larvae to pre-juvenile development. Herein, we found out that larvae couldnt abandon autophagy in both fasting and feeding conditions as larvae died earlier before pre-juvenile development despite feeding declaring the importance of autophagy not only to provide the cell with essential nutrients during starvation but also to get rid of cargos inside the eukaryotic cells. Briefly, if the larvae didnt recycle those cargos due to autophagy perturbations, they will die despite providing suitable conditions including food and acclimatization.

genetics↗

bioRxiv2017

Genetics and epigenetic alterations of hexaploid early generation derived from hybrid between Brassica napus and B. oleracea

Good fertility was observed previously in hexaploid derived from hybrid (ACC) between calona Zhongshuang 9(Brassica napus, 2n = 38, AACC) and kale SWU01 (B. oleracea var. acephala, 2n = 18, CC). However, the mechanism to underlying the character is unknown. In the present study, genetic and epigenetic alterations of S0, 6 S1, and 18 of their S2 progenies with hexaploid chromosome conformation (20A + 36C) were selected to compare with ACC and their parental species. 13.08% and 26.45% polymorphism alleles different from two parental species were identified in ACC via 58 SSR (simple sequence repeats) and 14 MSAP (methylation sensitive amplified polymorphism), respectively. 33.74% new alleles in DNA methylation, but not in DNA sequence were detected in S0 after chromosome doubling of ACC. DNA profilling revealed a little genetic but much epigenetic differences among S0, S1 and S2 generations. Genetic alteration was relatively stable, because only 8.09% and 3.21% alleles inheriated from ACC were changed in S2 and S1, respectively. While on average of 52.44 {+/-} 5.32% DNA methylation site inherited from ACC were detected in S1, and 41.52 {+/-} 9.04% in S2 due to dramatic epigenetic variance among early generations. New DNA methylation sites occurred in S0 would inheritated into the successive generations, but the frequency was decreased because some new site might be recovered. It demonstrated that much DNA methylation but a little DNA sequence variance was occurred in hexaploid early generation.

genetics↗