Synchronization of parallel intense electron beam accelerators based on single trigger generator.

In this study, the authors provide results of the precisely synchronized triggering of an intense electron beam accelerator (IEBA). The trigger generator was composed of a fractional-turn ratio saturable-pulse transformer and a compact six-stage Marx generator. The main switch of the IEBA was a corona-stabilized triggered switch (CSTS) based on the stabilized corona mechanism. The output voltage of a single IEBA exceeded 500 kV with less than 4 ns of jitter on a 50 Ω dummy load. We also conducted an experiment on the synchronous triggering of two IEBAs by using two independent trigger generators. The synchronization-related jitter was 6.1 ns, while the average time difference was 1.3 ns. We used this to attempt to trigger two parallel IEBAs by using a single trigger generator. The results showed a reduction in the synchronization-related jitter of 31% to 4.2 ns. The designs of the CSTS and the trigger generator guaranteed a precisely synchronous trigger by using a single trigger generator. Thus, the proposed method appears to be promising for accurately and synchronously triggering multiple IEBAs by using a single trigger generator. This provides an effective method to generate pulses with high power.

[Mechanism of Cistanches Herba in treatment of cancer-related fatigue based on network pharmacology and experimental verification].

This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 µg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.

Rps6ka2 enhances iMSC chondrogenic differentiation to attenuate knee osteoarthritis through articular cartilage regeneration in mice.

Articular cartilage (AC) is most susceptible to degeneration in knee osteoarthritis (OA); however, the existing treatments for OA do not target the core link of the pathogenesis-"decreased tissue cell function activity and extracellular matrix (ECM) metabolic disorders" for effective intervention. iMSC hold lower heterogeneity and great promise in biological research and clinical applications. Rps6ka2 may play an important role in the iMSC to treat OA. In this study, the CRISPR/Cas9 gene editing Rps6ka2-/- iMSC were obtained. Effect of Rps6ka2 on iMSC proliferation and chondrogenic differentiation was evaluated in vitro. An OA model was constructed in mice by surgical destabilization of medial meniscus (DMM). The Rps6ka2-/- iMSC and iMSC were injected into the articular cavity twice-weekly for 8 weeks. In vitro experiments showed that Rps6ka2 could promote iMSC proliferation and chondrogenic differentiation. In vivo results further confirmed that Rps6ka2 could improve iMSC viability to promote ECM production to attenuate OA in mice.

Cistanche tubulosa alleviates ischemic stroke-induced blood-brain barrier damage by modulating microglia-mediated neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) has both high morbidity and mortality. Previous research conducted by our group demonstrated that the bioactive ingredients of the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) have various pharmacological effects in treating nervous system diseases. However, the effect of CT on the blood-brain barrier (BBB) after IS are still unknown. AIM OF THE STUDY: This study aimed to identify CT's curative effect on IS and explore its underlying mechanism. MATERIALS AND METHODS: IS injury was established in a rat model of middle cerebral artery occlusion (MCAO). Gavage administration of CT at dosages of 50, 100, and 200 mg/kg/day was carried out for seven consecutive days. Network pharmacology was used for predicting the pathways and potential targets of CT against IS, and subsequent studies confirmed the relevant targets. RESULTS: According to the results, both neurological dysfunction and BBB disruption were exacerbated in the MCAO group. Moreover, CT improved BBB integrity and neurological function and protected against cerebral ischemia injury. Network pharmacology revealed that IS might involve neuroinflammation mediated by microglia. Extensive follow-up studies verified that MCAO caused IS by stimulating the production of inflammatory factors and microglial infiltration. CT was found to influence neuroinflammation via microglial M1-M2 polarization. CONCLUSION: These findings suggested that CT may regulate microglia-mediated neuroinflammation by reducing MCAO-induced IS. The results provide theoretical and experimental evidence for the efficacy of CT therapy and novel concepts for the prevention and treatment of cerebral ischemic injuries.

The translational landscape of human vascular smooth muscle cells identifies novel short open reading frame-encoded peptide regulators for phenotype alteration.

AIMS: The plasticity of vascular smooth muscle cells (VSMCs) enables them to alter phenotypes under various physiological and pathological stimuli. The alteration of VSMC phenotype is a key step in vascular diseases, including atherosclerosis. Although the transcriptome shift during VSMC phenotype alteration has been intensively investigated, uncovering multiple key regulatory signalling pathways, the translatome dynamics in this cellular process, remain largely unknown. Here, we explored the genome-wide regulation at the translational level of human VSMCs during phenotype alteration. METHODS AND RESULTS: We generated nucleotide-resolution translatome and transcriptome data from human VSMCs undergoing phenotype alteration. Deep sequencing of ribosome-protected fragments (Ribo-seq) revealed alterations in protein synthesis independent of changes in messenger ribonucleicacid levels. Increased translational efficiency of many translational machinery components, including ribosomal proteins, eukaryotic translation elongation factors and initiation factors were observed during the phenotype alteration of VSMCs. In addition, hundreds of candidates for short open reading frame-encoded polypeptides (SEPs), a class of peptides containing 200 amino acids or less, were identified in a combined analysis of translatome and transcriptome data with a high positive rate in validating their coding capability. Three evolutionarily conserved SEPs were further detected endogenously by customized antibodies and suggested to participate in the pathogenesis of atherosclerosis by analysing the transcriptome and single cell RNA-seq data from patient atherosclerotic artery samples. Gain- and loss-of-function studies in human VSMCs and genetically engineered mice showed that these SEPs modulate the alteration of VSMC phenotype through different signalling pathways, including the mitogen-activated protein kinase pathway and p53 pathway. CONCLUSION: Our study indicates that an increase in the capacity of translation, which is attributable to an increased quantity of translational machinery components, mainly controls alterations of VSMC phenotype at the level of translational regulation. In addition, SEPs could function as important regulators in the phenotype alteration of human VSMCs.

tModBase: deciphering the landscape of tRNA modifications and their dynamic changes from epitranscriptome data.

tRNA molecules contain dense, abundant modifications that affect tRNA structure, stability, mRNA decoding and tsRNA formation. tRNA modifications and related enzymes are responsive to environmental cues and are associated with a range of physiological and pathological processes. However, there is a lack of resources that can be used to mine and analyse these dynamically changing tRNA modifications. In this study, we established tModBase (https://www.tmodbase.com/) for deciphering the landscape of tRNA modification profiles from epitranscriptome data. We analysed 103 datasets generated with second- and third-generation sequencing technologies and illustrated the misincorporation and termination signals of tRNA modification sites in ten species. We thus systematically demonstrate the modification profiles across different tissues/cell lines and summarize the characteristics of tRNA-associated human diseases. By integrating transcriptome data from 32 cancers, we developed novel tools for analysing the relationships between tRNA modifications and RNA modification enzymes, the expression of 1442 tRNA-derived small RNAs (tsRNAs), and 654 DNA variations. Our database will provide new insights into the features of tRNA modifications and the biological pathways in which they participate.

Association of glutathione S-transferases (GSTT1, GSTM1 and GSTP1) genes polymorphisms with nonalcoholic fatty liver disease susceptibility: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Glutathione S-transferases (GSTs) genes single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD), but with inconsistent results across the current evidences. The present work was schemed to explore the association between GSTs genes polymorphisms and the NAFLD vulnerability via meta-analysis. METHODS: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wanfang were retrieved for eligible literatures previous to March 10, 2021. The odds ratio (OR) of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals (95%CIs) were computed to evaluate the strength of the associations. The quality of included studies were assessed via using Newcastle-Ottawa Scale (NOS). RESULTS: In total, 7 case-control studies encompassing 804 NAFLD patients and 1362 disease-free controls in this meta-analysis. Ultimately, this analysis included 6, 5 and 5 studies for GSTM1, GSTT1 and GSTP1 polymorphisms, respectively. The pooled data revealed that the GSTs genes SNPs had conspicuous associations with NAFLD susceptibility: for GSTM1, null versus present, OR = 1.46, 95%CI 1.20 to 1.79, P = .0002; for GSTT1, null versus present, OR = 1.34, 95%CI 1.06 to 1.68, P = .01; for GSTP1, Ile/Val or Val/Val versus Ile/Ile, OR = 1.60, 95%CI 1.23 to 2.09, P = .0005. CONCLUSION: This work revealed that the GSTM1 null, GSTT1 null and GSTP1-Val genotypes might be related to increased NAFLD susceptibility.

A compact, low jitter, high voltage trigger generator based on fractional-turn ratio saturable pulse transformer and its application.

In this paper, an all-solid-state high voltage trigger generator is developed, which is aimed at triggering a several gigawatts three-electrode spark gap of an intense electron beam accelerator (IEBA). As one of the most important parts for triggering the IEBA precisely, it is developed based on a fractional-turn ratio saturable pulse transformer and a compact six-stage Marx generator. A pulse of rising time 141 ns and amplitude 79.6 kV is obtained on the 1000 Ω dummy load. The trigger is operated at pulsed repetition frequency over 10 Hz for testing its operational stability. The jitter counted from the initial control signal to the falling edge of the pulse is 0.64 ns. In addition, experiments of three-minute continuous repetitive operations at 10 Hz and higher frequency are carried out. The results show that the trigger generator has high stability even in long-time operations. So far, it successfully applies to the main switch of IEBA with a breakdown voltage of over 500 kV, and a total system jitter of 6.7 ns is acquired.

Association of sorting and assembly machinery component 50 homolog gene polymorphisms with nonalcoholic fatty liver disease susceptibility.

BACKGROUND: Sorting and assembly machinery component 50 homolog (SAMM50) gene single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD), but with inconsistent results across the current evidence. The present work was schemed to explore the association between SAMM50 gene SNPs and NAFLD vulnerability via meta-analysis. METHODS: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang were retrieved for eligible literature previous to June 10, 2021. The odds ratios (ORs) of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals (95% CIs) were computed to evaluate the strength of the associations. The quality of included studies was assessed using Newcastle-Ottawa Scale (NOS). RESULTS: In total, 8 case-control studies encompassing 6297 NAFLD patients and 7306 disease-free controls in this meta-analysis. Ultimately, this analysis included 8, 6, and 5 studies for rs2143571, rs3761472, and rs738491 polymorphisms respectively. The pooled data revealed that the 3 polymorphisms had conspicuous associations with NAFLD susceptibility: rs2143571, A vs. G, OR=1.51, 95% CI, 1.37-1.66, P < .01; rs3761472, A vs. G, OR=1.50, 95% CI, 1.35-1.67, P < .01; rs738491, A vs. G, OR=1.51, 95% CI, 1.40-1.63, P < .01. CONCLUSION: This meta-analysis suggests that rs2143571, rs3761472, and rs738491 polymorphisms of the SAMM50 gene are appreciably associated with augmented risk of NAFLD vulnerability. It will provide the latest evidence to support the susceptibility of SAMM50 gene polymorphisms and NAFLD, and provide strategies for the prevention and treatment of NAFLD.

RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Elucidating the underlying mechanisms of this disease could provide new therapeutic strategies for treating HCC. Here, we identified a novel role of DEAD-box helicase 24 (DDX24), a member of the DEAD-box protein family, in promoting HCC progression. DDX24 levels were significantly elevated in HCC tissues and were associated with poor prognosis of HCC. Overexpression of DDX24 promoted HCC migration and proliferation in vitro and in vivo, whereas suppression of DDX24 inhibited both functions. Mechanistically, DDX24 bound the mRNA618-624nt of laminin subunit beta 1 (LAMB1) and increased its stability in a manner dependent upon the interaction between nucleolin and the C-terminal region of DDX24. Moreover, regulatory factor X8 (RFX8) was identified as a DDX24 promoter-binding protein that transcriptionally upregulated DDX24 expression. Collectively, these findings demonstrate that the RFX8/DDX24/LAMB1 axis promotes HCC progression, providing potential therapeutic targets for HCC. SIGNIFICANCE: The identification of a tumor-promoting role of DDX24 and the elucidation of the underlying regulatory mechanism provide potential prognostic indicators and therapeutic approaches to help improve the outcome of patients with hepatocellular carcinoma.

tsRFun: a comprehensive platform for decoding human tsRNA expression, functions and prognostic value by high-throughput small RNA-Seq and CLIP-Seq data.

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation.

Short-term prone positioning for severe acute respiratory distress syndrome after cardiopulmonary bypass: A case report and literature review.

BACKGROUND: Aortic dissection is a complex and dangerous cardiovascular disease, with many complications in the perioperative period, including severe acute respiratory distress syndrome (ARDS), which affects prognosis and increases mortality. Despite the effect of prone positioning (PP) in improving oxygenation in patients with severe ARDS, reports about PP early after cardiac surgery are few and such an option may be an issue in cardiac surgery patients because of the recent sternotomy. CASE SUMMARY: A 40-year-old male patient diagnosed with acute type A aortic dissection on October 22, 2021 underwent ascending artery replacement plus total aortic arch replacement plus stent elephant trunk implantation under cardiopulmonary bypass. Unfortunately, he developed ARDS on postoperative day 1. Despite comprehensive treatment with aggressive pulmonary protective ventilation, fluid management with continuous renal replacement therapy, the condition continued to deteriorate and rapidly progressed to severe ARDS with a minimum oxygenation index of 51. We are ready to implement salvage therapy, including PP and extracorporeal membrane oxygenation (ECMO). Due to the large amount of pericardial mediastinal and thoracic drainage after thoracotomy, ECMO may result in massive postoperative bleeding. Prolonged prone ventilation is often inappropriate after thoracotomy. Therefore, we chose short-term PP for < 6 h. Finally, the oxygenation index greatly improved and the diffuse exudation in both lungs of the patient was significantly reduced with short-term prone positioning. CONCLUSION: Intermittent short-term PP can improve early postoperative severe ARDS after acute aortic dissection.

Genome-wide identification of microRNA targets reveals positive regulation of the Hippo pathway by miR-122 during liver development.

Liver development is a highly complex process that is regulated by the orchestrated interplay of epigenetic regulators, transcription factors, and microRNAs (miRNAs). Owing to the lack of global in vivo targets of all miRNAs during liver development, the mechanisms underlying the dynamic control of hepatocyte differentiation by miRNAs remain elusive. Here, using Argonaute (Ago) high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) in the mouse liver at different developmental stages, we characterized massive Ago-binding RNAs and obtained a genome-wide map of liver miRNA-mRNA interactions. The dynamic changes of five clusters of miRNAs and their potential targets were identified to be differentially involved at specific stages, a dozen of high abundant miRNAs and their epigenetic regulation by super-enhancer were found during liver development. Remarkably, miR-122, a liver-specific and most abundant miRNA in newborn and adult livers, was found by its targetome and pathway reporter analyses to regulate the Hippo pathway, which is crucial for liver size control and homeostasis. Mechanistically, we further demonstrated that miR-122 negatively regulates the outcomes of the Hippo pathway transcription factor TEAD by directly targeting a number of hippo pathway regulators, including the coactivator TAZ and a key factor of the phosphatase complex PPP1CC, which contributes to the dephosphorylation of YAP, another coactivator downstream of the Hippo pathway. This study identifies for the first time the genome-wide miRNA targetomes during mouse liver development and demonstrates a novel mechanism of terminal differentiation of hepatocytes regulated by the miR-122/Hippo pathway in a coordinated manner. As the Hippo pathway plays important roles in cell proliferation and liver pathological processes like inflammation, fibrosis, and hepatocellular carcinoma (HCC), our study could also provide a new insight into the function of miR-122 in liver pathology.

Serum and Synovial Vancomycin Concentrations in Patients with Prosthetic Joint Infection after Intra-articular Infusion.

BACKGROUND AND OBJECTIVES: Vancomycin is one of the most commonly used antibiotics for intra-articular (IA) infusion in the treatment of prosthetic joint infection (PJI). This study aimed to preliminarily investigate the serum and synovial vancomycin concentrations in patients with PJI after IA infusion. METHODS: In total, 16 patients who developed PJI were enrolled in this study; 14 of the patients were treated with IA infusion of vancomycin postoperatively, while the other 2 patients received intravenous (IV) infusion of vancomycin alone. Chemiluminescent immunoassay assay (CLIA) and high-performance liquid chromatography (HPLC) were used to determine the serum and synovial vancomycin concentrations, respectively. RESULTS: Administration of vancomycin 0.5 g once daily (qd) IA maintained a high vancomycin trough concentration in synovial fluid before the next IA dose, regardless of whether it was given in combination with IV administration. The combination vancomycin 0.5 g qd IA + vancomycin 1 g every 12 h (q12h) IV yielded relatively good trough concentrations of vancomycin in both serum and synovial fluid. The mean trough serum vancomycin concentration of patients who used vancomycin 1 g q12h IV therapy was above 10 µg/mL; however, no vancomycin was detected in their synovial fluid. CONCLUSIONS: The rational use of IA vancomycin infusion may help to achieve effective therapeutic concentrations of vancomycin in the serum and synovial fluid of patients with PJI.

Identification and validation of inferior prognostic genes associated with immune signatures and chemotherapy outcome in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a group of heterogeneous hematological malignancies. We identified key genes as ITGAM and lncRNA ITGB2-AS1 through different bioinformatics tools. Furthermore, qPCR was performed to verify the expression level of essential genes in clinical samples. Retrospective research on 179 AML cases was used to investigate the relationship between the expression of ITGAM and the characteristics of AML. The critical gene relationship with immune infiltration in AML was estimated. The clinical validation and prognostic investigation showed that ITGAM, PPBP, and ITGB2-AS1 are highly expressed in AML (P < 0.001) and significantly associated with the overall survival in AML. Moreover, the retrospective research on 179 clinical cases showed that positive expression of ITGAM is substantially related to AML classification (P < 0.001), higher count of white blood cells (P < 0.01), and poor chemotherapy outcome (P < 0.05). Furthermore, based on grouping ITGAM as the high and low expression in TCGA-LAML profile, we found that genes in the highly expressed ITGAM group are mainly involved in immune infiltration and inflammation-related signaling pathways. Finally, we discovered that the expression level of ITGAM and lncRNA ITGB2-AS1 are not just closely related to the immune score and stromal score (P < 0.001) but also significantly positively correlated with various Immune signatures in AML (P < 0.001), indicating the association of these genes with immunosuppression in AML. The prediction of candidate drugs indicated that certain immunosuppressive drugs have potential therapeutic effects for AML. The critical genes could be used as potential biomarkers to evaluate the survival and prognosis of AML.

Complete chloroplast genome of Sinosenecio jishouensis D.G. Zhang, Ying Liu & Q. E. Yang (Asteraceae), a narrow endemic species in Wuling Mountain Region, China.

The first complete chloroplast genome (cp) of Sinosenecio jishouensis D.G. Zhang, Ying Liu & Q. E. Yang (Asteraceae) was sequenced and assembled in this study. The cp genome was 151,257 bp in length, including a large single-copy(LSC) region of 83,373 bp, a small single-copy (SSC) region of 18,178 bp, and a pair of inverted repeat (IR) regions of 24,853 bp each. These sequences encoded 134 genes, including 89 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic analysis based on 18 complete cp sequences revealed that S. jishouensis was closely related to Eclipta prostrata.

Identification of MiR-93-5p Targeted Pathogenic Markers in Acute Myeloid Leukemia through Integrative Bioinformatics Analysis and Clinical Validation.

Acute myeloid leukemia (AML) is a type of hematological malignancy with diverse genetic pathogenesis. Identification of the miR-93-5p targeted pathogenic markers could be useful for AML diagnosis and potential therapy. We collected 751 miR-93-5p targeted and AML-related genes by integrating the results of multiple databases and then used the expression profile of TCGA-LAML to construct a coexpression function network of AML WGCNA. Based on the clinical phenotype and module trait relationship, we identified two modules (brown and yellow) as interesting dysfunction modules, which have a significant association with cytogenetics risk and FAB classification systems. GO enrichment and KEGG analysis showed that these modules are mainly involved with cancer-associated pathways, including MAPK signal pathway, p53 signal pathway, JAK-STAT signal pathway, TGF-beta signaling pathway, mTOR signaling pathway, VEGF signaling pathway, both associated with the occurrence of AML. Besides, using the STRING database, we discovered the top 10 hub genes in each module, including MAPK1, ACTB, RAC1, GRB2, MDM2, ACTR2, IGF1R, CDKN1A, YWHAZ, and YWHAB in the brown module and VEGFA, FGF2, CCND1, FOXO3, IGFBP3, GSF1, IGF2, SLC2A4, PDGFBM, and PIK3R2 in the yellow module. The prognosis analysis result showed that six key pathogens have significantly affected the overall survival and prognosis in AML. Interestingly, VEGF with the most significant regulatory relationship in the yellow modules significantly positively correlated with the clinical phenotype of AML. We used qPCR and ELISA to verify miR-93-5p and VEGF expression in our clinical samples. The results exhibited that miR-93-5p and VEGF were both highly expressed in AML.

The cardiac translational landscape reveals that micropeptides are new players involved in cardiomyocyte hypertrophy.

Hypertrophic growth of cardiomyocytes is one of the major compensatory responses in the heart after physiological or pathological stimulation. Protein synthesis enhancement, which is mediated by the translation of messenger RNAs, is one of the main features of cardiomyocyte hypertrophy. Although the transcriptome shift caused by cardiac hypertrophy induced by different stimuli has been extensively investigated, translatome dynamics in this cellular process has been less studied. Here, we generated a nucleotide-resolution translatome as well as transcriptome data from isolated primary cardiomyocytes undergoing hypertrophy. More than 10,000 open reading frames (ORFs) were detected from the deep sequencing of ribosome-protected fragments (Ribo-seq), which orchestrated the shift of the translatome in hypertrophied cardiomyocytes. Our data suggest that rather than increase the translational rate of ribosomes, the increased efficiency of protein synthesis in cardiomyocyte hypertrophy was attributable to an increased quantity of ribosomes. In addition, more than 100 uncharacterized short ORFs (sORFs) were detected in long noncoding RNA genes from Ribo-seq with potential of micropeptide coding. In a random test of 15 candidates, the coding potential of 11 sORFs was experimentally supported. Three micropeptides were identified to regulate cardiomyocyte hypertrophy by modulating the activities of oxidative phosphorylation, the calcium signaling pathway, and the mitogen-activated protein kinase (MAPK) pathway. Our study provides a genome-wide overview of the translational controls behind cardiomyocyte hypertrophy and demonstrates an unrecognized role of micropeptides in cardiomyocyte biology.

ColorCells: a database of expression, classification and functions of lncRNAs in single cells.

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.