Lack of the CCT domain changes the ability of mango MiCOL14A to resist salt and drought stress in Arabidopsis.

CONSTANS (CO) is the key gene in the photoperiodic pathway that regulates flowering in plants. In this paper, a CONSTANS-like 14A (COL14A) gene was obtained from mango, and its expression patterns and functions were characterized. Sequence analysis shows that MiCOL14A-JH has an additional A base, which leads to code shifting in subsequent coding boxes and loss of the CCT domain. The MiCOL14A-JH and MiCOL14A-GQ genes both belonged to group Ⅲ of the CO/COL gene family. Analysis of tissue expression patterns showed that MiCOL14A was expressed in all tissues, with the highest expression in the leaves of seedling, followed by lower expression levels in the flowers and stems of adult leaves. However, there was no significant difference between different mango varieties. At different development stages of flowering, the expression level of MiCOL14A-GQ was the highest in the leaves before floral induction period, and the lowest at flowering stage, while the highest expression level of MiCOL14A-JH appeared in the leaves at flowering stage. The transgenic functional analysis showed that both MiCOL14A-GQ and MiCOL14A-JH induced delayed flowering of transgenic Arabidopsis. In addition, MiCOL14A-JH enhanced the resistance of transgenic Arabidopsis to drought stress, while MiCOL14A-GQ increased the sensitivity of transgenic Arabidopsis to salt stress. Further proteinprotein interaction analysis showed that MiCOL14A-JH directly interacted with MYB30-INTERACTING E3 LIGASE 1 (MiMIEL1), CBL-interacting protein kinase 9 (MiCIPK9) and zinc-finger protein 4 (MiZFP4), but MiCOL14A-GQ could not interact with these three stress-related proteins. Together, our results demonstrated that MiCOL14A-JH and MiCOL14A-GQ not only regulate flowering but also play a role in the abiotic stress response in mango, and the lack of the CCT domain affects the proteinprotein interaction, thus affecting the gene response to stress. The insertion of an A base can provide a possible detection site for mango resistance breeding.

Integrative genomic study of Chinese clear cell renal cell carcinoma reveals features associated with thrombus.

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with features that vary by ethnicity. A systematic characterization of the genomic landscape of Chinese ccRCC is lacking, and features of ccRCC associated with tumor thrombus (ccRCC-TT) remain poorly understood. Here, we applied whole-exome sequencing on 110 normal-tumor pairs and 42 normal-tumor-thrombus triples, and transcriptome sequencing on 61 tumor-normal pairs and 30 primary-thrombus pairs from 152 Chinese patients with ccRCC. Our analysis reveals that a mutational signature associated with aristolochic acid (AA) exposure is widespread in Chinese ccRCC. Tumors from patients with ccRCC-TT show a higher mutational burden and genomic instability; in addition, mutations in BAP1 and SETD2 are highly enriched in patients with ccRCC-TT. Moreover, patients with/without TT show distinct molecular characteristics. We reported the integrative genomic sequencing of Chinese ccRCC and identified the features associated with tumor thrombus, which may facilitate ccRCC diagnosis, prognosis and treatment.

Prognostic value of preoperative hematological markers combined with molecular pathology in patients with diffuse gliomas.

The prediction of clinical outcome for patients with infiltrative gliomas is challenging. Although preoperative hematological markers have been proposed as predictors of survival in glioma and other cancers, systematic investigations that combine these data with other relevant clinical variables are needed to improve prognostic accuracy and patient outcomes. We investigated the prognostic value of preoperative hematological markers, alone and in combination with molecular pathology, for the survival of 592 patients with Grade II-IV diffuse gliomas. On univariate analysis, increased neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), and decreased albumin-to-globulin ratio (AGR), all predicted poor prognosis in Grade II/III gliomas. Multivariate analysis incorporating tumor status based on the presence of IDH mutations, TERT promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups. NLR was an independent prognostic factor in Grade IV glioma. We therefore propose a prognostic model for diffuse gliomas based on the presence of IDH and TERT promoter mutations, 1p/19q codeletion, and NLR. This model classifies lower-grade gliomas into nine subgroups that can be combined into four main risk groups based on survival projections.

Leukaemic alterations of IKZF1 prime stemness and malignancy programs in human lymphocytes.

Somatic cells acquire stem cell-like properties during cancerous transformation; however, mechanisms through which committed cells develop stemness and malignancy remain largely unknown. Here we uncovered upregulated stem cell program in leukaemic lymphoblasts of patients with IKZF1 alterations by analysing the archived gene-expression profiling datasets. We then used a frequent IKZF1 deletion, IK6, as a model via transduction into human primitive haematopoietic cells, followed by xenotransplantation in mice. Immunophenotypically defined stem, pro-B, and immature/mature (IM/M)-B cells were collected from primary recipients for functional assay and transcriptome profiling. Successful reconstitution in secondary recipient mice revealed the stemness of IK6+ pro-B and IM/M-B cells. Upregulated stemness and malignancy programs in IK6+ cells confirmed IK6 effects. Interestingly, these programs corresponded to distinct canonical pathways. Remarkably, the pathway profile mapped in the modelled cells well mirrored that in patients' leukaemic cells; therefore, our study provides a seminal insight into the cancerous reprogramming of somatic cells.

Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing.

Esophageal squamous dysplasia is believed to be the precursor lesion of esophageal squamous cell carcinoma (ESCC); however, the genetic evolution from dysplasia to ESCC remains poorly understood. Here, we applied multi-region whole-exome sequencing to samples from two cohorts, 45 ESCC patients with matched dysplasia and carcinoma samples, and 13 tumor-free patients with only dysplasia samples. Our analysis reveals that dysplasia is heavily mutated and harbors most of the driver events reported in ESCC. Moreover, dysplasia is polyclonal, and remarkable heterogeneity is often observed between tumors and their neighboring dysplasia samples. Notably, copy number alterations are prevalent in dysplasia and persist during the ESCC progression, which is distinct from the development of esophageal adenocarcinoma. The sharp contrast in the prevalence of the 'two-hit' event on TP53 between the two cohorts suggests that the complete inactivation of TP53 is essential in promoting the development of ESCC.The pathogenesis of oesophageal squamous cell carcinoma is a multi-step process but the genetic determinants behind this progression are unknown. Here the authors use multi-region exome sequencing to comprehensively investigate the genetic evolution of precursor dysplastic lesions and untransformed oesophagus.

Quantum entanglement and criticality of the antiferromagnetic Heisenberg model in an external field.

By Lanczos exact diagonalization and the infinite time-evolving block decimation (iTEBD) technique, the two-site entanglement as well as the bipartite entanglement, the ground state energy, the nearest-neighbor correlations, and the magnetization in the antiferromagnetic Heisenberg (AFH) model under an external field are investigated. With increasing external field, the small size system shows some distinct upward magnetization stairsteps, accompanied synchronously with some downward two-site entanglement stairsteps. In the thermodynamic limit, the two-site entanglement, as well as the bipartite entanglement, the ground state energy, the nearest-neighbor correlations, and the magnetization are calculated, and the critical magnetic field h(c) = 2.0 is determined exactly. Our numerical results show that the quantum entanglement is sensitive to the subtle changing of the ground state, and can be used to describe the magnetization and quantum phase transition. Based on the discontinuous behavior of the first-order derivative of the entanglement entropy and fidelity per site, we think that the quantum phase transition in this model should belong to the second-order category. Furthermore, in the magnon existence region (h < 2.0), a logarithmically divergent behavior of block entanglement which can be described by a free bosonic field theory is observed, and the central charge c is determined to be 1.