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Mutations that affect phenotypes have been identified primarily as those that directly alter amino acid sequences or disrupt splice sites. However, some mutations not located in functionally important sites can also affect phenotypes, such as splice-site-creating mutations (SCMs). To investigate how frequent exon extension/shrinkage events induced by SCMs occur in normal individuals, we used personal genome sequencing data and transcriptome data of the corresponding individuals and identified 371 exon extension/shrinkage events in normal individuals. This number was about three times higher than the number of pseudo-exon activation events identified in the previous study. The average numbers of exon extension and exon shrinkage events in each sample were 3.3 and 11.2, respectively. We also evaluated the impact of exon extension/shrinkage events on the resulting transcripts and their protein products and found that 40.2% of the identified events may have possible functional impacts by either generating premature termination codons in transcripts or affecting protein domains. Our results indicated that a certain fraction of SCMs identified in this study can be pathogenic mutations by creating novel splice sites.

Pancreatic neuroendocrine tumor (pNET) is the second most common malignant tumors of the pancreas. Multiple endocrine neoplasia 1 ( MEN1) is the most frequently mutated gene in pNETs and MEN1-encoded protein, menin, is a scaffold protein that interacts with transcription factors and chromatin-modifying proteins to regulate various signaling pathways. However, the role of MEN1 in lipid metabolism has not been studied in pNETs. In this study, we perform targeted metabolomics analysis and find that MEN1 promotes the generation and oxidation of polyunsaturated fat acids (PUFAs). Meanwhile lipid peroxidation is a hallmark of ferroptosis, and we confirm that MEN1 promotes ferroptosis by inhibiting the activation of mTOR signaling which is the central hub of metabolism. We show that stearoyl-coA desaturase (SCD1) is the downstream of MEN1-mTOR signaling and oleic acid (OA), a metabolite of SCD1, recues the lipid peroxidation caused by MEN1 overexpression. The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, we find that BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pNETs that targets mTOR signaling. In addition, combined use everolimus with ferroptosis inducer, RSL3, possesses a more powerful ability to kill cells, which may provide a new strategy for the comprehensive therapy of pNETs.

Objectives: Rupture of a brain arteriovenous malformation (bAVM) can cause intracranial hemorrhage and severe clinical outcomes. At present, the mechanisms of bAVM-related hemorrhage are poorly understood. This study aimed to summarize the potential genetic risk factors for bAVM-related hemorrhage and appraise the methodological quality of existing genetic studies on bAVM-related hemorrhage using a cross-sectional design.Methods: A systematic literature search was conducted on genetic studies associated with bAVM-related hemorrhage published in PubMed, Embase, Web of Science, China National Knowledge Internet, and Wangfang databases, up to November 2022. Subsequently, a cross-sectional study was performed to describe the potential candidate genetic variants of bAVM associated with risk of hemorrhage and to evaluate the methodological quality of the identified studies using the Newcastle–Ottawa quality assessment scale and Q-genie tool.Results: Of the 1811 records identified in the initial search, nine studies met the filtering criteria and were included. Twelve single nucleotide polymorphisms (SNPs), including IL6 rs1800795, IL17A rs2275913, MMP9 rs9509, VEGFA rs1547651, and EPHB4 rs314353, rs314308, and rs314313, were associated with bAVM-related hemorrhage. However, only 12.5% of the evaluated SNPs showed statistical power> 0.80 (α = 0.05). Methodological quality assessment revealed significant flaws in the designs of the included studies, such as less reliable representativeness of recruited individuals, short follow-up periods in cohort studies, and less comparability between groups of hemorrhagic and non-hemorrhagic patients.Conclusion:IL1B, IL6, IL17A, APOE, MMP9, VEGFA and EPHB4 were potentially associated with bAVM-related hemorrhage. The methodological designs of the analyzed studies required improvement in order to obtain more reliable results. Regional alliances and rare disease banks need to be established to recruit large numbers of bAVM patients (especially familial and extreme-trait cases) in a multicenter, prospective cohort study with an adequate follow-up period. Furthermore, it is important to use advanced sequencing techniques and efficient measures to filter candidate genetic variants.

Camellia granthamiana is a rare and endangered plant peculiar to China, and a total of 5 plants have been found at present. Based on the next generation sequencing, the whole chloroplast (Cp) genome of (Camellia granthamiana Sealy) of Camellia oleifera was constructed.In this study, the complete chloroplast (cp) genome of Camellia granthamiana was assembled based on next generation sequencing.The cp genome was 157,001 bp in length, including a large single copy (LSC) region of 70,387 bp, a small single copy (SSC) region of 18,296 bp and a pair of inverted repeats (IRs) of 52,082 bp. The genome contained 135 genes, including 90 protein-coding genes, 37 tRNA genes and 8 ribosomal RNA genes. The majority of these gene species occurred as a single copy.

Tree fern Alsophila spinulosa is an endangered relic plant in the world. It is currently on the International Union for Conservation of Nature (IUCN) red list of threatened species. In this study, we first assembled the complete chloroplast (cp) genome of A. spinulosa by Illumina paired-end reads data. The whole genome was 156,661 bp, consisting of a pair of inverted repeats of 24,364 bp, large single copy region and a small single copy region (70,352 and 21,624 bp in length, respectively). The cp genome contained 133 genes, including 92 protein-coding genes, 33 trRNA genes, and eight rRNA genes. The overall GC content of the whole genome was 40.4%. A neighbour-joining phylogenetic analysis demonstrated a close relationship between A. spinulosa and Cystoathyrium chinense Ching.

Davidia involucrata Baill. is a kind of tertiary paleotropical plant floristic relic species unique to China. This rare plant is disappearing due to poor adaptability and serious poaching. We first assembled the complete chloroplast (cp) genome of Davidia involucrata Baill. by Illumina paired-end reads data. The whole genome was 169,085 bp, consisting of a pair of inverted repeats of 169,379 bp, large single copy region and a small single copy region (96,712 and 67,667 bp in length, respectively). The cp genome contained 90 genes, including 64 protein-coding genes, 22 trRNA genes and 4 rRNA genes. The overall GC content of the whole genome was 38.04%. A neighbor-joining phylogenetic analysis demonstrated a close relationship between Davidia involucrata Baill. and Nyssa yunnanensis.

Ginkgo biloba L. is the oldest relict plant among the gymnosperms, left after the quaternary glacial movement. There are few living G. biloba and few old trees over a hundred years old. It is currently on the International Union for Conservation of Nature (IUCN) red list of threatened species. In this study, we first assembled the complete chloroplast (cp) genome of G. biloba L. by Illumina paired-end reads data. The whole genome was 156,988 bp, consisting of a pair of inverted repeats of 34,056 bp, large and small single copy regions of 56,819 and 22,763 bp in length, respectively. The cp genome contained 131 genes, including 84 protein-coding genes, 31 trRNA genes and 5 rRNA genes. The overall GC content of the whole genome was 39.6%. A neighbour-joining phylogenetic analysis demonstrated a close relationship between G. biloba L. and Cycas revoluta.