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Abstract Background The MYCN amplification is a defining hallmark of high-risk neuroblastoma. Due to irregular oncogenes orchestration, tumor cells exhibit distinct fatty acid metabolic features from non-tumor cells. However, the function of MYCN in neuroblastoma fatty acid metabolism reprogramming remains unknown. Methods Gas Chromatography-Mass Spectrometer (GC-MS) was used to find the potential target fatty acid metabolites of MYCN. Real-time PCR (RT-PCR) and clinical bioinformatics analysis was used to find the related target genes. The function of the identified target gene ELOVL2 on cell growth was detected through CCK-8 assay, Soft agar colony formation assay, flow Cytometry assay and mouse xenograft. Chromatin immunoprecipitation (ChIP) and Immunoprecipitation-Mass Spectrometer (IP-MS) further identified the target gene and the co-repressor of MYCN. Results The fatty acid profile of MYCN-depleted neuroblastoma cells identified docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-tumor activity, significantly increased after MYCN depletion. Compared with MYCN single-copy neuroblastoma cells, DHA level was significantly lower in MYCN-amplified neuroblastoma cells. RT-PCR and clinical bioinformatics analysis discovered that MYCN interfered DHA accumulation via ELOVL fatty acid elongase 2 (ELOVL2) which is a rate-limiting enzyme of cellular DHA synthesis. Enforced ELOVL2 expression in MYCN-amplified neuroblastoma cells led to decreased cell growth and counteracted the growth-promoting effect of MYCN overexpression both in vitro and vivo. ELOVL2 Knockdown showed the opposite effect in MYCN single-copy neuroblastoma cells. In primary neuroblastoma, high ELOVL2 transcription correlated with favorable clinical tumor biology and patient survival. The mechanism of MYCN-mediated ELOVL2 inhibition contributed to epigenetic regulation. MYCN recruited PRC1 (Polycomb repressive complex 1), catalysed H2AK119ub (histone 2A lysine 119 monoubiquitination) and inhibited subsequent ELOVL2 transcription. Conclusions The tumor suppressive properties of DHA and ELOVL2 are repressed by the MYCN and PRC1 jointly, which suggests a new epigenetic mechanism of MYCN-mediated fatty acid regulation and indicates PRC1 inhibition as a potential novel strategy to activate ELOVL2 suppressive functions.

Background: Traumatic brain injury (TBI) is a brain function change caused by external forces, which is one of the main causes of death and disability worldwide. The aim of this study was to identify early diagnostic markers and potential therapeutic targets for TBI.Methods: Differences between TBI and controls in GSE89866 and GSE104687 were analyzed. The two groups of differentially expressed genes (DEGs) were combined for coexpression analysis, and the modules of interest were performed using enrichment analysis. Hub genes were identified by calculating area under curve (AUC) values of module genes, PPI network analysis, and functional similarity. Finally, the difference in immune cell infiltration between TBI and control was calculated by ssGSEA.Results: A total of 4,817 DEGs were identified in GSE89866 and 1,329 DEGs in GSE104687. They were clustered into nine modules. The genes of modules 1, 4, and 7 had the most crosstalk and were identified as important modules. Enrichment analysis revealed that they were mainly associated with neurodevelopment and immune inflammation. In the PPI network constructed by genes with top 50 AUC values in module genes, we identified the top 10 genes with the greatest connectivity. Among them, down-regulated RPL27, RPS4X, RPL23A, RPS15A, and RPL7A had similar functions and were identified as hub genes. In addition, DC and Tem were significantly up-regulated and down-regulated between TBI and control, respectively.Conclusion: We found that hub genes may have a diagnostic role for TBI. Molecular dysregulation mechanisms of TBI are associated with neurological and immune inflammation. These results may provide new ideas for the diagnosis and treatment of TBI.

Travel route options for passengers can provide data support for railway line planning, passenger flow organisation, and train operation establishment. A critical review of the literature indicates that previous studies mainly focused on choices offered by a single railway network path without much consideration of China’s normal-speed and high-speed integrated railway network and the effect of train timetable on passengers’ travel choice. In this study, a method based on generalised cost is proposed to discover the valid routes of passenger travel in the integrated network of China’s normal-speed and high-speed railways. After quantifying the effects of train fare, travel time, transfer, travel convenience, comfort, and other factors on the generalised expenses of passengers, this study presents a generalised cost determination method when individuals select an option from different seats of different trains of specific railway transport products. Theoretically, the valid routes considering the train schedule is defined, and a valid route search algorithm is designed using the deep traversal idea in a new valid route searching network. Considering the Lanzhou-Beijing passenger travel routes as an example, this study verifies the practicability of the generalised cost calculation method, as well as that of the valid routes search method.

Preliminary studies have shown that endothelial-monocyte-activating polypeptide-II (EMAP-II) and temozolomide (TMZ) alone can exert cytotoxic effects on glioma cells. This study explored whether EMAP-II can enhance the cytotoxic effects of TMZ on glioma stem cells (GSCs) and the possible mechanisms associated with Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)-mediated mitophagy facilitated by miR-24-3p regulation. The combination of TMZ and EMAP-II significantly inhibited GSCs viability, migration, and invasion, resulting in upregulation of the autophagy biomarker microtubule-associated protein one light chain 3 (LC3)-II/I but down-regulation of the proteins P62, TOMM 20 and CYPD, changes indicative of the occurrence of mitophagy. BNIP3 expression increased significantly in GSCs after treatment with the combination of TMZ and EMAP-II. BNIP3 overexpression strengthened the cytotoxic effects of EMAP-II and TMZ by inducing mitophagy. The combination of EMAP-II and TMZ decreased the expression of miR-24-3p, whose target gene was BNIP3. MiR-24-3p inhibited mitophagy and promoted proliferation, migration and invasion by down-regulating BNIP3 in GSCs. Furthermore, nude mice subjected to miR-24-3p silencing combined with EMAP-II and TMZ treatment displayed the smallest tumors and the longest survival rate. According to the above results, we concluded that EMAP-II enhanced the cytotoxic effects of TMZ on GSCs' proliferation, migration and invasion both in vitro and in vivo.

Vigorous angiogenesis is one of the reasons for the poor prognosis of glioma. A number of studies have shown that long non-coding RNA can affect a variety of biological behaviors of tumors. However, the influence of long non-coding RNAs on glioma vascular endothelial cells remains unclear. To simulate the glioma microenvironment, we applied glioma-conditioned medium to human cerebral microvascular endothelial cells. The long non-coding RNA PVT1 was found to be highly expressed in glioma vascular endothelial cells. Cell Counting Kit-8, migration, and tube formation assays showed that PVT1 overexpression promoted glioma vascular endothelial cells proliferation, migration, and angiogenesis. We also found that PVT1 overexpression upregulated the expression of the autophagy-related proteins Atg7 and Beclin1, which induced protective autophagy. Bioinformatics software and dual-luciferase system analysis confirmed that PVT1 acts by targeting miR-186. In addition, our study showed that miR-186 could target the 3′ untranslated region of Atg7 and Beclin1 to decrease their expression levels, thereby inhibiting glioma-conditioned human cerebral microvascular endothelial cell autophagy. In conclusion, PVT1 overexpression increased the expression of Atg7 and Beclin1 by targeting miR-186, which induced protective autophagy, thus promoting glioma vascular endothelial cell proliferation, migration, and angiogenesis. Therefore, PVT1 and miR-186 can provide new therapeutic targets for future anti-angiogenic treatment of glioma.

The plant homeodomain finger (PHD finger) protein, a type of zinc finger protein extensively distributed in eukaryotes, plays diverse roles in regulating plant growth and development. While PHD finger proteins have been identified in various species, their functions remain largely unexplored in pea (Pisum sativum). In this study, we identified 84 members of the PHD finger gene family in pea, which displayed an uneven distribution across seven chromosomes. Through a comprehensive analysis using data from Arabidopsis thaliana and Medicago truncatula, we categorized the PHD finger proteins into 20 subfamilies via phylogenetic tree analysis. Each subfamily exhibited distinct variations in terms of quantity, genetic structure, conserved domains, and physical and chemical properties. Collinearity analysis revealed conserved evolutionary relationships among the PHD finger genes across the three different species. Furthermore, we identified the conserved and important roles of the subfamily M members in anther development. RT-qPCR and in situ hybridization revealed high expression of the pea subfamily M members PsPHD11 and PsPHD16 in microspores and the tapetum layer. In conclusion, this analysis of the PHD finger family in pea provides valuable guidance for future research on the biological roles of PHD finger proteins in pea and other leguminous plants.

BackgroundShoulder-hand syndrome (SHS) is a common complication after stroke, and SHS-induced pain significantly hampers patients’ overall recovery. As an alternative therapy for pain relief, acupuncture has certain advantages in alleviating pain caused by SHS after stroke. However, choosing the best treatment plan from a variety of acupuncture options is still a serious challenge in clinical practice. Therefore, we conducted this Bayesian network meta-analysis to comprehensively compare the effectiveness of various acupuncture treatment methods.MethodsWe systematically searched for randomized controlled trials (RCTs) of acupuncture treatment in patients with post-stroke SHS published in PubMed, Embase, Cochrane, and Web of Science until 9 March 2023. We used the Cochrane bias risk assessment tool to assess the bias risk in the included original studies.ResultsA total of 50 RCTs involving 3,999 subjects were included, comprising 19 types of effective acupuncture interventions. Compared to single rehabilitation training, the top three interventions for VAS improvement were floating needle [VAS = −2.54 (95% CI: −4.37 to −0.69)], rehabilitation + catgut embedding [VAS = −2.51 (95% CI: −4.33 to −0.68)], and other multi-needle acupuncture combinations [VAS = −2.32 (95% CI: −3.68 to −0.94)]. The top three interventions for improving the Fugl–Meyer score were eye acupuncture [Meyer = 15.73 (95% CI: 3.4627.95)], other multi-needle acupuncture combinations [Meyer = 12.22 (95% CI: 5.1919.34)], and traditional western medicine + acupuncture + traditional Chinese medicine [Meyer = 11.96 (95% CI: −0.59 to 24.63)].ConclusionMultiple acupuncture methods are significantly effective in improving pain and upper limb motor function in post-stroke SHS, with relatively few adverse events; thus, acupuncture can be promoted.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, CRD42023410957.

Edible Macadamia is one of the most important commercial nut trees cultivated in many countries, but its large tree size and long juvenile period pose barriers to commercial cultivation. The short domestication period and well-annotated genome of Macadamia integrifolia create great opportunities to breed commercial varieties with superior traits. Recent studies have shown that members of the phosphatidylethanolamine binding protein (PEBP) family play pivotal roles in regulating plant architecture and flowering time in various plants. In this study, thirteen members of MiPEBP were identified in the genome of M. integrifolia, and they are highly similarity in both motif and gene structure. A phylogenetic analysis divided the MiPEBP genes into three subfamilies: MFT-like, FT-like and TFL1-like. We subsequently identified two TERMINAL FLOWER 1 homologues from the TFL1-like subfamily, MiTFL1 and MiTFL1-like, both of which were highly expressed in stems and vegetative shoots, while MiTFL1-like was highly expressed in young leaves and early flowers. A subcellular location analysis revealed that both MiTFL1 and MiTFL1-like are localized in the cytoplasm and nucleus. The ectopic expression of MiTFL1 can rescue the early-flowering and terminal-flower phenotypes in the tfl1–14 mutant of Arabidopsis thaliana, and it indicates the conserved functions in controlling the inflorescence architecture and flowering time. This study will provide insight into the isolation of PEBP family members and the key targets for breeding M. integrifolia with improved traits in plant architecture and flowering time.

Soybean is one of the most important legume crops that can provide the rich source of protein and oil for human beings and livestock. In the twenty-one century, the total production of soybean is seriously behind the needs of a growing world population. Cultivated soybean [Glycine max (L.) Merr.] was domesticated from wild soybean (G. soja Sieb. and Zucc.) with the significant morphology and organ size changes in China around 5,000 years ago, including twisted stems to erect stems, small seeds to large seeds. Then it was spread worldwide to become one of the most popular and important crops. The release of the reference soybean genome and omics data provides powerful tools for researchers and breeders to dissect the functional genes and apply the germplasm in their work. Here, we summarized the function genes related to yield traits and organ size in soybean, including stem growth habit, leaf size and shape, seed size and weight. In addition, we also summarized the selection of organ traits during soybean domestication. In the end, we also discussed the application of new technology including the gene editing on the basic research and breeding of soybean, and the challenges and research hotspots in the future.

The VILLIN (VLN) protein is an important regulator of the actin cytoskeleton, which orchestrates many developmental processes and participates in various biotic and abiotic responses in plants. Although the VLN gene family and their potential functions have been analyzed in several plants, knowledge of VLN genes in soybeans and legumes remains rather limited. In this study, a total of 35 VLNs were characterized from soybean and five related legumes. Combining with the VLN sequences from other nine land plants, we categorized the VLN gene family into three groups according to phylogenetic relationships. Further detailed analysis of the soybean VLNs indicated that the ten GmVLNs were distributed on 10 of the 20 chromosomes, and their gene structures and protein motifs showed high group specificities. The expression pattern analysis suggested that most GmVLNs are widely expressed in various tissues, but three members have a very high level in seeds. Moreover, we observed that the cis−elements enriched in the promoters of GmVLNs are mainly related to abiotic stresses, hormone signals, and developmental processes. The largest number of cis−elements were associated with light responses, and two GmVLNs, GmVLN5a, and GmVLN5b were significantly increased under the long light condition. This study not only provides some basic information about the VLN gene family but also provides a good reference for further characterizing the diverse functions of VLN genes in soybeans.

This paper focuses on the nonlinear system identification problem, which is a basic premise of control and fault diagnosis. For Hammerstein output-error nonlinear systems, we propose an auxiliary model-based multi-innovation fractional stochastic gradient method. The scalar innovation is extended to the innovation vector for increasing the data use based on the multi-innovation identification theory. By establishing appropriate auxiliary models, the unknown variables are estimated and the improvement in the performance of parameter estimation is achieved owing to the fractional-order calculus theory. Compared with the conventional multi-innovation stochastic gradient algorithm, the proposed method is validated to obtain better estimation accuracy by the simulation results.