Alternative pre-mRNA splicing yields functionally distinct splice variants in regulating normal cell differentiation as well as cancer development. The putative tumor suppressor gene GT198 (PSMC3IP), encoding a protein also known as TBPIP and Hop2, has been shown to regulate steroid hormone receptor-mediated transcription and to stimulate homologous recombination in DNA repair. Here, we have identified 6 distinct GT198 splice variant transcripts generated by alternative promoter usage or alternative splicing. Various splice variant transcripts preserve a common open reading frame, which encodes the DNA binding domain of GT198. The splice variants act as dominant negatives to counteract wild-type GT198 activity in transcription and to abolish Rad51 foci formation during radiation-induced DNA damage. In fallopian tube cancer, we have identified 44 point mutations in GT198 clustered in 2 mutation hotspot sequences. The mutation hotspots coincide with the regulatory sequences responsible for alternative splicing, strongly supporting that imbalanced alternative splicing is a selected consequence in cancer. In addition, splice variant-associated cytoplasmic expression is found in tumors carrying germline or somatic GT198 mutations. An altered alternative splicing pattern with increased variants is also present in lymphoblastoid cells derived from familial breast cancer patients carrying GT198 germline mutations. Furthermore, GT198 and its variant are reciprocally expressed during mouse stem cell differentiation. The constitutive expression of the GT198 variant but not the wild type induces tumor growth in nude mice. Our results collectively suggest that mutations in the GT198 gene deregulate alternative splicing. Defective alternative splicing promotes antagonizing variants and in turn induces a loss of the wild type in tumorigenesis. The study highlights the role of alternative splicing in tumor suppressor gene inactivation.

Electrocatalytic hydrogen evolution reaction, the cornerstone of the emerging hydrogen economy, can be essentially facilitated by robustly heterostructural electrocatalysts. Herein, we report a highly active and stably heterostructural electrocatalyst consisting of NiCoP nanowires decorated with CoP nanoparticles on a nickel foam (NiCoP–CoP/NF) for effective hydrogen evolution. The CoP nanoparticles are strongly interfaced with NiCoP nanowires producing abundant electrocatalytically active sites. Combined with the integrated catalyst design, NiCoP–CoP/NF affords a remarkable hydrogen evolution performance in terms of high activity, enhanced kinetics, and outstanding durability in an alkaline electrolyte, superior to most of the Co (or Ni)-phosphide-based catalysts reported previously. Density functional theory calculations demonstrate that there is an interfacial effect between NiCoP and CoP, which allows a preferable hydrogen adsorption and thus contributes to the significantly enhanced performance. Furthermore, an electrolyzer employing NiCoP–CoP/NF as the cathode and RuO2/NF as the anode (NiCoP–CoP/NF||RuO2/NF) exhibits excellent water-splitting activity and outstanding durability, which is comparable to that of the benchmark Pt–C/NF||RuO2/NF electrolyzer.

Graphene-like two-dimensional carbon nanosheets with properly modulated compositions and porosity are of particular importance for robust capacitance harvesting. Nevertheless, the large-scale and cost-effective production of such nanostructures still remains a great challenge. Herein, we innovatively produce nitrogen-doped porous carbon nanosheets using pine nut shells, an abundant biomass waste, as the precursor, under the synergetic effect of KOH and melamine during the activation process. The sole activation of the precursors with KOH can produce only traditional activated carbon particles of several micrometers, while interestingly, the extra introduction of melamine results in nitrogen-doped porous carbon nanosheets possessing high tunability. By construction of a two-electrode configuration, the supercapacitors with optimal nanosheets as the electrode materials can deliver a superior specific capacitance of 324 F g –1 at 0.05 A g–1, outstanding rate capability of 258 F g–1 at 20 A g–1, and extraordinary cyclic stability of 94.6% after 10 000 cycles at 2 A g–1 in an aqueous electrolyte of 6 M KOH. Such a facile strategy proposed here may contribute to new possibilities of synthesizing graphene-like porous carbon nanosheets in a sustainable manner for energy-related applications.

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