Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

The goal in similarity search is to find objects similar to a specified query object given a certain similarity criterion. Although useful in many areas, such as multimedia retrieval, pattern recognition, and computational biology, to name but a few, similarity search is not yet supported well by commercial DBMS. This may be due to the complex data types involved and the needs for flexible similarity criteria seen in real applications. We propose an efficient disk-based metric access method, the Space-filling curve and Pivot-based B + -tree (SPB-tree), to support a wide range of data types and similarity metrics. The SPB-tree uses a small set of so-called pivots to reduce significantly the number of distance computations, uses a spacefilling curve to cluster the data into compact regions, thus improving storage efficiency, and utilizes a B + -tree with minimum bounding box information as the underlying index. The SPB-tree also employs a separate random access file to efficiently manage a large and complex data. By design, it is easy to integrate the SPB-tree into an existing DBMS. We present efficient similarity search algorithms and corresponding cost models based on the SPB-tree. Extensive experiments using real and synthetic data show that the SPB-tree has much lower construction cost, smaller storage size, and can support more efficient similarity queries with high accuracy cost models than is the case for competing techniques. Moreover, the SPB-tree scales sublinearly with growing dataset size.

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Post-transcriptional RNA modifications critically regulate various biological processes. N4-acetylcytidine (ac4C) is an epi-transcriptome, which is highly conserved in all species. However, the in vivo physiological functions and regulatory mechanisms of ac4C remain poorly understood, particularly in mammals. In this study, we demonstrate that the only known ac4C writer, N-acetyltransferase 10 (NAT10), plays an essential role in male reproduction. We identified the occurrence of ac4C in the mRNAs of mouse tissues and showed that ac4C undergoes dynamic changes during spermatogenesis. Germ cell-specific ablation of Nat10 severely inhibits meiotic entry and leads to defects in homologous chromosome synapsis, meiotic recombination and repair of DNA double-strand breaks during meiosis. Transcriptomic profiling revealed dysregulation of functional genes in meiotic prophase I after Nat10 deletion. These findings highlight the crucial physiological functions of ac4C modifications in male spermatogenesis and expand our understanding of its role in the regulation of specific physiological processes in vivo.

Layered double hydroxides (LDHs) have attracted much attention in supercapacitors because of the high specific surface area and theoretical capacitance. However, the bad cycling stability has always been their Achilles’ heel that restrains their further application. In this paper, a small amount of unactive and single-valence element zinc, which has no contribution to the capacitance of electrodes, was first doped into NiCo-LDHs through two consecutive electrodeposition processes only within 30 min. With a polyaniline (PANI) nanolayer as the interlayer, an ultrathin NiCoZn-LDH nanoplate network was well-anchored on the carbon cloth surface. The slight Zn2+ doping dramatically enhanced the cycling performance of LDHs with little capacitance decay. Zn2+ doping enhanced the cyclic structural stability of NiCoZn-LDHs, while the PANI layer strengthened the interface interaction between LDHs and the current collector. By controlling the doping content of Zn2+ at 2.9%, the composite electrode achieved the best performance with a high specific capacitance of 1749 F g–1 and an ultralong life span with 89% capacitance retention after 40,000 charge–discharge cycles. This work offers a novel strategy to fast build LDH-based supercapacitors with both high specific capacitance and cycling performance.