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We have investigated the internal structure of the open- and hidden-charmed (DD∗/D¯D∗) molecules in the unified framework. We first fit the experimental lineshape of the Tcc+ state and extract the DD∗ interaction, from which the Tcc+ is assumed to arise solely. Then we obtain the DD‾∗ interaction by charge conjugation. Our results show that the DD‾∗ interaction is attractive but insufficient to form X(3872) as a bound state. Instead, its formation requires the crucial involvement of the coupled channel effect between the DD¯∗ and cc¯ components, although the cc¯ accounts for approximately 1% only. Besides X(3872), we have obtained a higher-energy state around 3957.9 MeV with a width of 16.7 MeV, which may be a potential candidate for the X(3940). In JPC=1+- sector, we have found two states related to the iso-scalar X̃(3872) and hc(2P), respectively. Our combined study provides valuable insights into the nature of these DD∗/DD¯∗ exotic states.

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A novel framework is proposed to extract near-threshold resonant states from finite-volume energy levels of lattice QCD and is applied to elucidate structures of the positive parity D_{s}. The quark model, the quark-pair-creation mechanism and D^{(*)}K interaction are incorporated into the Hamiltonian effective field theory. The bare 1^{+} cs[over ¯] states are almost purely given by the states with heavy-quark spin bases. The physical D_{s0}^{*}(2317) and D_{s1}^{*}(2460) are the mixtures of bare cs[over ¯] core and D^{(*)}K component, while the D_{s1}^{*}(2536) and D_{s2}^{*}(2573) are almost dominated by bare cs[over ¯]. Furthermore, our model reproduces the clear level crossing of the D_{s1}^{*}(2536) with the scattering state at a finite volume.

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Recently, the hidden charm tetraquark states Zcs(3985) and Zcs(4000) with strangeness were observed by the BESIII and LHCb collaborations, respectively, which are great breakthroughs for exploring exotic quantum chromodynamics (QCD) structures. The first and foremost question is whether they are the same state. In this work, we explore the implications of the narrower state Zcs(3985) in BESIII and the wider one Zcs(4000) in LHCb as two different states. Within a solvable nonrelativistic effective field theory, we include the possible violations of heavy quark spin symmetry and SU(3) flavor symmetry in a comprehensive approach. If Zcs(3985) and Zcs(4000) are two different states, our results show that Zcs(4000)/Zcs(3985) is the pure (|D‾s∗D〉+/-|D‾sD∗〉)/2 state, and the SU(3) flavor partner of Zc(3900) is Zcs(4000) rather than the Zcs(3985). Another two important consequences are the existence of a tensor D‾s∗D∗ resonance with mass about 4126 MeV and width 13 MeV, and the suppression of the decay mode Zcs(3985)→J/ψK. The two consequences can be tested in experiments and distinguish the two-state interpretation from the one-state scheme.

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INTRODUCTION: Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired clonal disease of hematopoietic stem cells. It is caused by somatic mutation of the X-linked PIGA gene, resulting in a deficient expression of glycosylphosphatidylinositol-anchored proteins (GPI-APs). In this study, we aimed to explore the diagnostic value of next-generation sequencing (NGS) and potential molecular basis in PNH patients. METHODS: Genomic DNA of 85 PNH patients was analyzed by a 114-gene NGS panel. RESULTS: Mutational analysis of PIGA identified 124 mutations in 92% PNH patients, including 101 distinct mutations and 23 recurrent mutations. Among them, 102 mutations were newly reported. Most mutations were located in exon 2 of PIGA gene, and truncated mutation was the most common one. Other mutations were detected in 26 out of 85 cases, including five cases of DNMT3A variants, four cases of ASXL1 variants, and four cases of U2AF1 variants. Clonal analysis was performed in one case and outlined a linear evolution pattern in classic PNH. There was a positive correlation between number of PIGA mutations and fraction of GPI-APs deficient granulocytes. CONCLUSION: The detection of PIGA mutations and additional variants by targeted NGS not only shed light on the genetic characteristics of PNH, but also provided an important reference value in the diagnosis of PNH at molecular level.

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Cooperative regulation among multiple microRNAs (miRNAs) is a complex type of posttranscriptional regulation in human; however, the global view of the system-level regulatory principles across cancers is still unclear. Here, we investigated miRNA-miRNA cooperative regulatory landscape across 18 cancer types and summarized the regulatory principles of miRNAs. The miRNA-miRNA cooperative pan-cancer network exhibited a scale-free and modular architecture. Cancer types with similar tissue origins had high similarity in cooperative network structure and expression of cooperative miRNA pairs. In addition, cooperative miRNAs showed divergent properties, including higher expression, greater expression variation and a stronger regulatory strength towards targets and were likely to regulate cancer hallmark-related functions. We found a marked rewiring of miRNA-miRNA cooperation between various cancers and revealed conserved and rewired network miRNA hubs. We further identified the common hubs, cancer-specific hubs and other hubs, which tend to target known anticancer drug targets. Finally, miRNA cooperative modules were found to be associated with patient survival in several cancer types. Our study highlights the potential of pan-cancer miRNA-miRNA cooperative regulation as a novel paradigm that may aid in the discovery of tumorigenesis mechanisms and development of anticancer drugs.

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Gene regulatory network perturbations contribute to the development and progression of cancer, however, molecular determinants that mediate transcriptional perturbations remain a fundamental challenge for cancer biology. We show that transcriptional perturbations are widely mediated by long noncoding RNAs (lncRNAs) via integration of genome-wide transcriptional regulation with paired lncRNA and gene expression profiles. Systematic construction of an LncRNA Modulator Atlas in Pan-cancer (LncMAP) reveals distinct types of lncRNA regulatory molecules, which are expressed in multiple tissues, exhibit higher conservation. Strikingly, cancers with similar tissue origin share lncRNA modulators which perturb the regulation of cell cycle and immune response-related functions. Furthermore, we identified a large number of pan-cancer lncRNA modulators with potential clinical significance, which are differentially expressed in cancer or are strongly correlated with drug sensitivity across cell lines. Further stratification of cancer patients based on lncRNA-mediated transcriptional perturbations identifies subtypes with distinct survival rates. Finally, we made a user-friendly web interface available for exploring lncRNA-mediated transcriptional perturbations across cancer types. Our study provides a systems-level dissection of lncRNA-mediated regulatory perturbations in cancer, and also presents a valuable tool and resource for investigating the function of lncRNAs in cancer.

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Recent advances in transcriptome sequencing have made it possible to distinguish ubiquitously expressed long non-coding RNAs (UE lncRNAs) from tissue-specific lncRNAs (TS lncRNAs), thereby providing clues to their cellular functions. Here, we assembled and functionally characterized a consensus lncRNA transcriptome by curating hundreds of RNA-seq datasets across normal human tissues from 16 independent studies. In total, 1,184 UE and 2,583 TS lncRNAs were identified. These different lncRNA populations had several distinct features. Specifically, UE lncRNAs were associated with genomic compaction and highly conserved exons and promoter regions. We found that UE lncRNAs are regulated at the transcriptional level (with especially strong regulation of enhancers) and are associated with epigenetic modifications and post-transcriptional regulation. Based on these observations we propose a novel way to predict the functions of UE and TS lncRNAs through analysis of their genomic location and similarities in epigenetic modifications. Our characterization of UE and TS lncRNAs may provide a foundation for lncRNA genomics and the delineation of complex disease mechanisms.

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