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Background Hepatocellular carcinoma (HCC) remains a major challenge for public health worldwide. Considering the great heterogeneity of HCC, more accurate prognostic models are urgently needed. To identify a robust prognostic gene signature, we conduct this study. Materials and methods Level 3 mRNA expression profiles and clinicopathological data were obtained in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC). GSE14520 dataset from the gene expression omnibus (GEO) database was downloaded to further validate the results in TCGA. Differentially expressed mRNAs between HCC and normal tissue were investigated. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan–Meier curve, multivariate Cox regression analysis, nomogram, and decision curve analysis (DCA) were used to assess the prognostic capacity of the six-gene signature. The prognostic value of the gene signature was further validated in independent GSE14520 cohort. Gene Set Enrichment Analyses (GSEA) was performed to further understand the underlying molecular mechanisms. The performance of the prognostic signature in differentiating between normal liver tissues and HCC were also investigated. Results A novel six-gene signature (including CSE1L, CSTB, MTHFR, DAGLA, MMP10, and GYS2) was established for HCC prognosis prediction. The ROC curve showed good performance in survival prediction in both the TCGA HCC cohort and the GSE14520 validation cohort. The six-gene signature could stratify patients into a high- and low-risk group which had significantly different survival. Cox regression analysis showed that the six-gene signature could independently predict OS. Nomogram including the six-gene signature was established and shown some clinical net benefit. Furthermore, GSEA revealed several significantly enriched oncological signatures and various metabolic process, which might help explain the underlying molecular mechanisms. Besides, the prognostic signature showed a strong ability for differentiating HCC from normal tissues. Conclusions Our study established a novel six-gene signature and nomogram to predict overall survival of HCC, which may help in clinical decision making for individual treatment.

What causes the disparity in biodiversity among regions is a fundamental question in biogeography, ecology, and evolutionary biology. Evolutionary and biogeographic processes (speciation, extinction, dispersal) directly determine species richness patterns, and can be studied using integrative phylogenetic approaches. However, the strikingly high richness of East Asia relative to other Northern Hemisphere regions remains poorly understood from this perspective. Here, for the first time, we test two general hypotheses (older colonization time, faster diversification rate) to explain this pattern, using the plant tribe Lysimachieae (Primulaceae) as a model system. We generated a new time-calibrated phylogeny for Lysimachieae (13 genes, 126 species), to estimate colonization times and diversification rates for each region and to test the relative importance of these two factors for explaining regional richness patterns. We find that neither time nor diversification rates alone explain richness patterns among regions in Lysimachieae. Instead, a new index that combines both factors explains global richness patterns in the group and their high East Asian biodiversity. Based on our results from Lysimachieae, we suggest that the high richness of plants in East Asia may be explained by a combination of older colonization times and faster diversification rates in this region.

IntroductionN6-methyladenosine (m6A), the most prominent mRNA modification, plays a critical role in many physiological and pathological processes. However, the roles of m6A RNA modification in hepatocellular carcinoma (HCC) remain largely unknown.Materials and MethodsWe investigated the mRNA expression and clinical significance of m6A-related genes using data from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma cohort. Mutation, copy number variation (CNV), methylation, differential expression, and gene ontology analyses, gene set enrichment analysis and the construction of a competing endogenous RNA (ceRNA) regulatory network were performed to investigate the underlying mechanisms of the aberrant expression of m6A-related genes.Resultsm6A-related genes were frequently dysregulated in cancers but with a cancer-specific pattern. METTL3, YTHDF2, and ZC3H13 were found to be independent prognostic factors of overall survival (OS); however, only METTL3 was found to be an independent prognostic factor of recurrence-free survival (RFS). Joint effects analysis showed the predictive capacity of combining METTL3, YTHDF2, and ZC3H13 for HCC OS. Then the potential mechanisms of METTL3 were further explored due to its prognostic role in both OS and RFS. CNV and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of METTL3 in HCC. Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC.ConclusionsOur study identified several m6A-related genes, especially METTL3, that could be potential prognostic biomarkers in HCC.

Objective To examine the differences and similarities among primary biliary cholangitis (PBC) with positive and negative expression of autoantibodies (anti-mitochondrial antibodies AMA and AMA-M2, antinuclear antibodies anti-gp210, and anti-sp100). Methods Clinical and pathological data of 85 PBC in patients who underwent liver puncture biopsy were retrospectively collected from January 2016 to September 2018 at the Second Hospital of Nanjing. The differences in clinical and pathological indexes of PBC between autoantibody negative and positive groups were analyzed by SPSS 25.0, and the patients’ previous autoantibody indexes were collected for follow-up. Results The average age of 85 PBC patients was (52.2 ± 9.2) years old, including 15 males (17.6%) and 70 females (82.4%), with a male-to-female ratio of 1:4.7. Fifty-nine autoantibody-positive cases and 26 autoantibody-negative cases were 50 (84.7%) AMA positive, 51 (86.4%) AMA-M2 positive, 21 (35.6%) anti-gp210 positive, and 15 (25.4%) anti-sp100 positive. The distribution of CK7-positive hepatocytes and the degree of bile duct injury in the portal area of PBC patients in the antibody-negative group were lower than those in the antibody-positive group ( P  < 0.05). There was no significant difference in the distribution of interface inflammation, plasma cell grade, ductular reaction, and fibrosis between the two groups. When the autoimmune antibodies were reexamined at 2 months–7 years (median time 1 year), AMA, AMA-M2, anti-gp210, and anti-sp100 were still negative in 16 antibody-negative patients. Conclusions The pathological symptoms and diagnostic patterns of autoantibody-negative and positive PBC were generally comparable. In this study, the pathological manifestations of antibody-negative PBC were similar to those of antibody-positive PBC, but the lymphocyte aggregation in antibody-negative PBC was more severe than that in antibody-positive PBC, while the degree of bile duct injury and CK7-positive hepatocytes were milder than that in antibody-positive PBC, suggesting that the overall pathological changes of antibody-negative PBC were slightly milder than those of antibody-positive PBC.

Actinomycin V, extracted and separated from marine-derived actinomycete Streptomyces sp., as the superior potential replacement of actinomycin D (which showed defect for its hepatotoxicity) has revealed an ideal effect in the suppression of migration and invasion in human breast cancer cells as referred to in our previous study. In this study, the involvement of p53 in the cell cycle arrest and pro-apoptotic action of actinomycin V was investigated in human non-small-cell lung carcinoma A549 cells. Results from the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay showed that cytotoxic activity of actinomycin V on A549 cells (with wild-type p53) was stronger than the NCI-H1299 cells (p53-deficient). Actinomycin V upregulated both of the protein and mRNA expression levels of p53, p21Waf1/Cip1 and Bax in A549 cells. For this situation, actinomycin V decreased the M-phase related proteins (Cdc2, Cdc25A and Cyclin B1) expression, arrested cells in G2/M phase and subsequently triggered apoptosis by mediating the Bcl-2 family proteins’ expression (Bax and Bcl-2). Furthermore, the effects of cell cycle arrest and apoptosis in A549 cells which were induced by actinomycin V could be reversed by the pifithrin-α, a specific inhibitor of p53 transcriptional activity. Collectively, our results suggest that actinomycin V causes up-regulation of p53 by which the growth of A549 cells is suppressed for cell cycle arrest and apoptosis.

The genus Primula is extremely diverse in the east Himalaya-Hengduan Mountains (HHM) in China as a result of rapid radiation. In order to overcome the difficulty of morphological classification of this genus, we surveyed three plastid regions (rbcL, matK, and trnH-psbA) and two nuclear markers (ITS and ITS2) from 227 accessions representing 66 Primula species across 18 sections, to assess their discriminatory power as barcodes. We found that ITS alone or combined with plastid regions showed the best discrimination across different infrageneric ranks and at species level. We suggest rbcL + matK + ITS as the first choice at present to barcode Primula plants. Although the present barcoding combination performed poorly in many closely related species of Primula, it still provided many new insights into current Primula taxonomy, such as the underlying presence of cryptic species, and several potential improper taxonomic treatments. DNA barcoding is one useful technique in the integrative taxonomy of the genus Primula, but it still requires further efforts to improve its effectiveness in some taxonomically challenging groups.

To explore the willingness, needs, and factors influencing participation in medication decision-making among elderly patients with multi-morbidities, caregivers, and healthcare professionals. A phenomenological research method was used to conduct semi-structured interviews with elderly patients with multi-morbidities, caregivers, and healthcare professionals. The purposive sampling method was used to select geriatric patients with multi-morbidities, their caregivers, and healthcare workers from March to July 2024 in the Geriatrics, Cardiology, Endocrinology, Respiratory, and Nephrology Departments of a tertiary hospital in Shanxi Province as the study subjects. The Colaizzi 7-step analysis method was used to analyze, summarize, and refine themes from the interview data. Twelve elderly patients with multi-morbidities, nine caregivers, and seven healthcare professionals were interviewed. Three themes and nine sub-themes were identified, as follows: (1) willingness to participate in decision-making (large differences in willingness and discrepancies between willingness and reality); (2) the current status of multi-morbidity management (lack of guidelines, healthcare systems and decision-making support systems); and (3) factors influencing participation in decision-making (bias in the power structure, lack of information exchange, insufficient knowledge and awareness of shared decision-making by healthcare workers, differences in patients' self-management initiative and medication-focused motivations). Elderly patients with multi-morbidities were affected by multiple impediments to participation in medication decision-making. Healthcare professionals should continue to improve their shared decision-making awareness and ability, provide patients with targeted decision-making needs, solve decision-making problems, and promote the implementation of shared decision-making in elderly patients with multi-morbidities.

Current and historical events have both affected the current distribution patterns and intraspecific divergence of plants. While numerous studies have focused on the Qinghai-Tibetan Plateau (QTP), the impacts of such events on the flora of subtropical China remain poorly understood. Subtropical China is famous for its highly complex topography and the limited impact from glaciation during the Pleistocene; this may have resulted in a different genetic legacy for species in this region compared to fully glaciated areas. We used plastid and nuclear DNA sequence data and distribution modeling to analyze the divergence patterns and demographic history of Primula obconica Hance, a widespread herbaceous montane species in subtropical China. The phylogenetic analysis revealed two major lineages (lineage A and lineage B), representing a west-east split into the Yunnan and Eastern groups, and the Sichuan and Central groups, respectively. The Eastern and Central groups comprised relatively new derived haplotypes. Nested Clade Analysis and Bayesian Skyline Plot analyses both indicated that P. obconica mainly experienced a gradual expansion of populations. In addition, the simulated distribution of P. obconica during the Last Glacial Maximum was slightly larger than its present-day distribution. Our results are the first to identify a west-east migration of P. obconica. The gradual expansion pattern and a larger potential distribution range in cold periods detected for P. obconica indicate that the population expansion of this species is consistent with the phalanx model. In addition, the current patterns of genetic differentiation have persisted as a result of the extensive environmental heterogeneity that exists in subtropical China.

The subspecies subsp exhibits pharmacological properties akin to the traditional Chinese medicinal plant ( subsp (Hance) Verdc.). In this report, we unveil the plastid genome of subsp . The genome spans 156,322 base pairs (bp), comprising a large single-copy (LSC) region of 86,633 bp, a small single-copy (SSC) region of 18,219 bp, and two distinct inverted repeat regions (IRs) of 25,735 bp each. Annotation process cataloged a total of 111 genes within this genome, including 77 protein-coding genes, 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. The overall guanine-cytosine (GC) content of the plastome is 35.5%. Phylogenetic analysis utilizing maximum-likelihood (ML) based on 16 complete plastid genomes reveals a close clustering of three taxa, namely subsp , subsp , and . Notably, subsp clusters with as a sister group, distinct from subsp . These findings highlight significant differences between the plastid genomes of the two subspecies, laying the foundation for future research on the identification of medicinal herbs and germplasm resources related to these subspecies.

Species-rich genus Primula L. is a typical plant group with which to understand genetic variance between species in different levels of relationships. Chloroplast genome sequences are used to be the information resource for quantifying this difference and reconstructing evolutionary history. In this study, we reported the complete chloroplast genome sequence of Primula sinensis and compared it with other related species. This genome of chloroplast showed a typical circular quadripartite structure with 150,859 bp in sequence length consisting of 37.2% GC base. Two inverted repeated regions (25,535 bp) were separated by a large single-copy region (82,064 bp) and a small single-copy region (17,725 bp). The genome consists of 112 genes, including 78 protein-coding genes, 30 tRNA genes and four rRNA genes. Among them, seven coding genes, seven tRNA genes and four rRNA genes have two copies due to their locations in the IR regions. The accD and infA genes lacking intact open reading frames (ORF) were identified as pseudogenes. SSR and sequence variation analyses were also performed on the plastome of Primula sinensis , comparing with another available plastome of P. poissonii . The four most variable regions, rpl36–rps8 , rps16–trnQ , trnH–psbA and ndhC–trnV , were identified. Phylogenetic relationship estimates using three sub-datasets extracted from a matrix of 57 protein-coding gene sequences showed the identical result that was consistent with previous studies. A transcript found from P. sinensis transcriptome showed a high similarity to plastid accD functional region and was identified as a putative plastid transit peptide at the N-terminal region. The result strongly suggested that plastid accD has been functionally transferred to the nucleus in P. sinensis .