Gemcitabine (dFdC), a modified deoxycytidine (dC) widely used in tumor treatment, is a prodrug that is phosphorylated to generate mono-, di-, and triphosphates. The triphosphate (dFdCTP) is ...incorporated into DNA to terminate DNA synthesis in cancer. Some incorporated dFdC nucleotides can be partially removed by the 3'-5' exonuclease activity, namely its editing function, and the others escape the editing. However, whether there is an active mechanism for dFdC to escape the editing remains unclear. We have first discovered that unlike dFdC, its mono-, di-, and triphosphates can inhibit the 3'-5' exonuclease of DNA polymerase I, suppress editing, and allow the active escaping mechanism, whereas its polymerase activity is not remarkably affected. As such, these phosphates can prevent the removal of the incorporated dFdC residue, thereby actively blocking DNA extension and synthesis. The inhibition efficiency of these phosphates follows the increased order of the mono-, di-, and triphosphates of gemcitabine (dFdC < dFdCMP < dFdCDP < dFdCTP). In addition, after the deletion of the 3'-5' exonuclease of cellular DNA polymerase I, the
mutant is more sensitive to dFdCTP than is wild-type
. Our new discovery of the ability of these dFdC phosphates to inhibit exonuclease activity suggests a novel anticancer mechanism of gemcitabine and its phosphate derivatives.
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•ImprovementinterfacequalitybetweenCsPbI2BrperovskiteandcarbonelectrodebyDelta-2:2-bis ...(1,3-dithiazole).•Achievementofhighpowerconversionefficiency(13.78%)withthearchitectureITO/SnO2/SnCl2/CsPbI2Br/Carbon.•Increasingthestabilityofcarbon-basedCsPbI2BrPSCsbecauseofinterfacemodification.
All-inorganic perovskite materials, typically CsPbI2Br, have received widespread attention owing to their outstanding thermal stability than that of organic/inorganic hybrid counterparts. However, the power conversion efficiency (PCE) of CsPbI2Br perovskite solar cell (PSC) is far lower than its theoretical value. In this study, to further improve the PCE, a sulfur-rich small molecule material (delta-2:2-bis (1,3-dithiazole)), is used to modify the interface between CsPbI2Br and carbon electrode. Encouragingly, the carbon-based CsPbI2Br PSCs achieve a high PCE of 13.78% than the control of 10.40%, which is the best performance of carbon-based CsPbI2Br PSC among the literature report at present. The remarkable reduction of defect density and suppression recombination should be responsible for the PCE improvement. This work proposes a simple and effective strategy to enhance the efficiency of all-inorganic carbon-based CsPbI2Br PSCs.
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•The Cs2PtI6 is proposed as a multifunction perovskite modifier.•The perovskite crystal quality is remarkable improved.•The recombination of charge carriers is dramatically ...suppressed.•A superb PCE of 23.56% is achieved with planar architecture.•Less than 10% degradation of initial PCE is achieved.
The planar organic–inorganic hybrid perovskite solar cells (PSCs) have in recent years had remarkable success due to their superior optoelectronic performance. However, their power conversion efficiency is significantly inferior compared to mesoporous structure PSCs. Unlike most other advances focusing on non-perovskite materials to improve device performance, herein a multifunctional double perovskite material, Cs2PtI6, is proposed as the grain boundary modifier of organic–inorganic hybrid perovskite films. Results show three main benefits of introducing Cs2PtI6 into perovskite films: (1) it prompts growth of perovskite crystals, resulting in improved crystallinity and enlarged crystals; (2) it suppresses the trap assisted recombination at grain boundaries thanks to the formation of heterojunction and interface passivation; (3) it raises the efficiency of carrier collection and transport at grain boundaries owing to the high carrier mobility of Cs2PtI6. Consequently, a PCE of 23.56% is achieved. The unencapsulated devices show less than 10% degradation compared to the initial performance after storage in ambient (≈ 30%) humidity for 2000 h. This study outlines a simple yet effective strategy for boosting the performance of planar PSCs.
Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating ...independently and with different period lengths. Here we showed that heterogeneity in circadian period is heritable and used a multi-omics approach to investigate underlying mechanisms. By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. We also discovered differentially co-expressed gene networks that were functionally associated with period length. We further demonstrated that global differential DNA methylation bidirectionally regulated these same gene networks. Interestingly, we found that depletion of DNMT1 and DNMT3A had opposite effects on circadian period, suggesting non-redundant roles in circadian gene regulation. Together, our findings identify novel gene candidates involved in periodicity, and reveal DNA methylation as an important regulator of circadian periodicity.
Plants utilize energy from sunlight to perform photosynthesis in chloroplast, an organelle that could be damaged by solar UV radiation. The ultraviolet-B (UV-B) photoreceptor UVR8 is required for ...UV-B perception and signal transduction. However, little is known about how UVR8 influence chloroplast development under UV-B radiation. Here, we characterized tomato UVR8 gene (SlUVR8) and our results indicated that SlUVR8 facilitate plant acclimation to UV-B stress by orchestrating expression of the UVB-responsive genes (HY5 and CHS) and accumulating UV-absorptive compounds. In addition, we also discovered that SlUVR8 promotes fruit chloroplast development through enhancing accumulation of transcription factor GOLDEN2-LIKE2 (SlGLK2) which determines chloroplast and chlorophyll levels. Furthermore, UV-B radiation could increase expression of SlGLK2 and its target genes in fruits and leaves. SlUVR8 is required for UVB-induced SlGLK2 expression. Together, our work not only identified the conserved functions of SlUVR8 gene in response to UV-B stress, but also uncovered a novel role that SlUVR8 could boost chloroplast development by accumulating SlGLK2 proteins.
All-inorganic CsPbI2Br perovskite material has attracted enormous attention for high-performance photovoltaics due to its excellent thermal stability and suitable bandgap. Furthermore, carbon-based ...CsPbI2Br perovskite solar cells (C-PSCs) not only further improve the thermal and moisture stability of the devices but also reduce production costs and simplify procedure processes. However, the usage of carbon electrodes introduces new problems, such as poor interface contact and energy level mismatch. Herein, the N-phenylthiourea (PTU) with S atom and N-phenylurea (PU) with O atom are applied for interface modification materials in C-PSCs. The atoms S and O can combine with Pb and enhance perovskite crystallinity as well as manage the energy level. Meanwhile, after passivation of PTU and PU, the defect state density of the perovskite layer is significantly reduced, thereby inhibiting the recombination of carriers. The Voc of the device with PTU increases from 1.12 V to 1.22 V, 9% improvement over the control device. The efficiency of CsPbI2Br C-PSCs is improved from 10.29% to 13.01% after modification. Furthermore, the stability of the device has been improved. This study provides a strategy for developing highly efficient and stable C-PSCs.
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•PTU aligns the energy level between CsPbI2Br and carbon.•PTU optimizes CsPbI2Br film quality and device stability.•It achieves a champion PCE 13.01% based on carbon-based CsPbI 2Br PSCs.
Power conversion efficiencies (PCEs) of up to 25.5 % have been reported for perovskite solar cells (PSCs). Thus, they have shown great potential for commercial applications. Therefore, simplifying ...technological process and reducing production costs have been a widespread concern among scientific and industrial communities. In this study, PSCs are prepared with the simplest device architecture (FTO/MAPbI3/carbon). A high‐quality perovskite film with few interface defects and good carrier transport is obtained by tuning the p‐n properties, matching energy levels, and enhancing carrier collection and transport. A PCE of 12.01 % is achieved, which is the best reported to date for this device structure. The device also shows excellent long‐term stability, owing to the elimination of charge transport layers and the usage of hydrophobic materials. This study provides a new approach to reduce production costs and simplify production of PSCs.
Pure and simple: Perovskite solar cells (PSCs) with the simplest architecture (FTO/MAPbI3/carbon) are prepared by using a strategy without additional steps and exhibit a power conversion efficiency of over 12 %. This result provides a new way to reduce production costs and simplify production of PSCs.
Whole-genome microarrays with large-insert clones designed to determine DNA copy number often show variation in hybridization intensity that is related to the genomic position of the clones. We found ...these 'genomic waves' to be present in Illumina and Affymetrix SNP genotyping arrays, confirming that they are not platform-specific. The causes of genomic waves are not well-understood, and they may prevent accurate inference of copy number variations (CNVs). By measuring DNA concentration for 1444 samples and by genotyping the same sample multiple times with varying DNA quantity, we demonstrated that DNA quantity correlates with the magnitude of waves. We further showed that wavy signal patterns correlate best with GC content, among multiple genomic features considered. To measure the magnitude of waves, we proposed a GC-wave factor (GCWF) measure, which is a reliable predictor of DNA quantity (correlation coefficient = 0.994 based on samples with serial dilution). Finally, we developed a computational approach by fitting regression models with GC content included as a predictor variable, and we show that this approach improves the accuracy of CNV detection. With the wide application of whole-genome SNP genotyping techniques, our wave adjustment method will be important for taking full advantage of genotyped samples for CNV analysis.
Fibrosarcoma is an aggressive and highly metastatic cancer of the connective tissue, for which effective therapeutic methods are limited. Recently, there has been a renewed interest in small ...molecular compounds from natural products in the treatment of cancer. In the present study, we investigated the compound, scutellarein, extracted from the perennial herb Scutellaria lateriflora, and it was found to possess anticancer potential. Cell proliferation assay and cell cycle analysis revealed that the proliferation rate of HT1080 human fibrosarcoma cells was significantly suppressed by treatment with scutellarein through the induction of apoptosis. Moreover, an in vivo experiment using Balb/c nude mice revealed that the volume and weight of the tumors were markedly reduced following treatment with scutellarein. We also analyzed the effects of scutellarein on the markers of metastasis, using the HT1080 cells. The results indicated that scutellarein potently inhibited cell migration, invasion and the expression and activity of matrix metalloproteinase (MMP)-2, -9 and -14. Furthermore, MMP activation and cell survival were suppressed due to the scutellarein-mediated downregulation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation. In conclusion, our data suggest that scutellarein has the ability to attenuate the development of fibrosarcoma and inhibit cancer cell metastasis.
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