Follicular lymphoma (FL) is an incurable malignancy1, with transformation to an aggressive subtype being a critical event during disease progression. Here we performed whole genome or exome sequencing on 10 FL-transformed FL pairs, followed by deep sequencing of 28 genes in an extension cohort and report the key events and evolutionary processes governing initiation and transformation. Tumor evolution occurred through either a ‘rich’ or ‘sparse’ ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histones, JAK-STAT signaling, NF-κB signaling and B-cell development genes. Longitudinal analyses revealed chromatin regulators (CREBBP, EZH2 and MLL2) as early driver genes, whilst mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides novel insights into the genetic basis of follicular lymphoma, the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations within the CPC represents an attractive therapeutic strategy.

All-carbon tetrasubstituted olefins have been found in numerous biologically important compounds and organic materials. However, regio-and stereocontrolled construction of this structural motif still constitutes a significant synthetic challenge. Here, we show that a modular and regioselective synthesis of all-carbon tetrasubstituted olefins can be realized via alkenyl halide-or triflate-mediated palladium/norbornene (Pd/NBE) catalysis, which is enabled by a modified NBE containing a C2 amide moiety. This new NBE co-catalyst effectively suppressed undesired cyclopropanation pathways, which have previously been a main obstacle for developing such reactions. Diverse cyclic and acyclic alkenyl bromides or triflates with a wide range of functional groups can be employed as substrates. Various substituents can be introduced at the alkene C1 and C2 positions regioselectively simply by changing the coupling partners. Initial mechanistic studies provide insights on the rate-limiting step as well as the structure of the actual active ligand in this system.

To identify the factors controlling high-quality deep shale gas reservoirs and the exploration and development potential of the Lower Paleozoic marine shale in the Sichuan Basin, the sedimentary environment of deep shale was comprehensively analysed using core thin sections, scanning electron microscopy, gamma ray spectrometry logging, and elemental logging data. In addition, the geological conditions of deep shale gas accumulation and the effect of tectonic processes on the preservation conditions are discussed based on the experimental data of mineral composition analysis, geochemical features, and reservoir spatial characteristics. (1) The sedimentary environment changes from an anoxic water environment to an oxygen-rich oxidizing environment from bottom to top in the Wufeng-Longmaxi Formation in southern Sichuan. The deep shale gas reservoir shows overpressure and rich gas characteristics, namely, high formation pressure (2.0~2.2), high porosity (20%~55%), and high gas content (4.0~5.0 m3/t). (2) The favourable sedimentary environment has a higher hydrocarbon generation potential and deposits of rich organic matter and siliceous particles. During the hydrocarbon generation process, the rich organic matter generates a large number of organic pores and a large specific surface area, which provides the main reservoir and adsorption space for free and adsorbed shale gas. A large number of biogenic siliceous particles provide a solid rock support framework for the shale reservoir, thereby maintaining excellent reservoir physical properties. (3) Late and small stratigraphic uplifts result in a short shale gas escape time and favourable preservation conditions. Additionally, the small-scale faults and a high-angle intersection between the fracture strike and the geostress direction are conducive to the preservation of shale gas. (4) A high formation pressure coefficient, a sedimentary environment rich in organic siliceous deep-water continental shelf microfacies, and a relatively stable tectonic structure are conducive to the accumulation of deep shale gas.

Nanopores have become one of the most important tools for single-molecule sensing, but the challenge for selective detection of specific biomolecules still exists. In this contribution, we develop a new technique for sensing carcinoembryonic antigen (CEA), one of the important cancer biomarkers, using solid-state nanopores as a tool. The method is based on the specific affinity between aptamer (Apt) modified magnetic Fe3O4–Au nanoparticles (MNPs) and CEA, and the formed CEA–Apt–MNPs and remaining Apt–MNPs can transport the nanopores by applying a positive potential after magnetic separation. Due to the obvious particle size difference between CEA–Apt–MNPs and Apt-MPs, their corresponding blockage signals could be distinguished completely by the degree of the current decline. Moreover, the frequency of the blockage signals for CEA–Apt–MNPs is proportional to the concentration of CEA within certain limits, indicating that our designed nanopore sensing strategy can quantitatively detect CEA in complex samples. This work demonstrates that our designed nanopore-based strategy can be used for CEA sensing with good selectivity and sensitivity and also can be used to analyze other protein biomarkers for early diagnosis and monitoring of cancer, though the detection limit (0.6 ng/mL) is not relatively low. In future works, we plan to improve our detection limit by the improvement of the nanopipette preparation technology and detection method.

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