Materials undergoing reversible solid-to-solid martensitic phase transformations are desirable for applications in medical sensors and actuators, eco-friendly refrigerators and energy conversion devices. The ability to pass back and forth through the phase transformation many times without degradation of properties (termed 'reversibility') is critical for these applications. Materials tuned to satisfy a certain geometric compatibility condition have been shown to exhibit high reversibility, measured by low hysteresis and small migration of transformation temperature under cycling. Recently, stronger compatibility conditions called the 'cofactor conditions' have been proposed theoretically to achieve even better reversibility. Here we report the enhanced reversibility and unusual microstructure of the first martensitic material, Zn45Au30Cu25, that closely satisfies the cofactor conditions. We observe four striking properties of this material. (1) Despite a transformation strain of 8%, the transformation temperature shifts less than 0.5 °C after more than 16,000 thermal cycles. For comparison, the transformation temperature of the ubiquitous NiTi alloy shifts up to 20 °C in the first 20 cycles. (2) The hysteresis remains approximately 2 °C during this cycling. For comparison, the hysteresis of the NiTi alloy is up to 70 °C (refs 9, 12). (3) The alloy exhibits an unusual riverine microstructure of martensite not seen in other martensites. (4) Unlike that of typical polycrystal martensites, its microstructure changes drastically in consecutive transformation cycles, whereas macroscopic properties such as transformation temperature and latent heat are nearly reproducible. These results promise a concrete strategy for seeking ultra-reliable martensitic materials.

We demonstrate a new method for the direct conversion of heat to electricity using the recently discovered multiferroic alloy, Ni45Co5Mn40Sn101. This alloy undergoes a low hysteresis, reversible martensitic phase transformation from a nonmagnetic martensite phase to a strongly ferromagnetic austenite phase upon heating. When biased by a suitably placed permanent magnet, heating through the phase transformation causes a sudden increase of the magnetic moment to a large value. As a consequence of Faraday’s law of induction, this drives a current in a surrounding circuit. Theory predicts that under optimal conditions the performance compares favorably with the best thermoelectrics. Because of the low hysteresis of the alloy, a promising area of application of this concept appears to be energy conversion at small ΔT, suggesting a possible route to the conversion of the vast amounts of energy stored on earth at small temperature difference. We postulate other new methods for the direct conversion of heat to electricity suggested by the underlying theory.

The hepatitis B virus (HBV) X protein (HBx) has a key role in the molecular pathogenesis of HBV-related hepatocellular carcinoma (HCC). However, the mechanism of HBx-mediated hepatocarcinogenesis remains to be elucidated. In this study, we aimed to better understand the effects of HBx on gene-expression profiles that participate in hepatocarcinogenesis and the mechanism by which HBx regulates these genes. Differentially expressed genes between L02-HBx and L02-Vector control cells were identified by microarray and validated using quantitative real-time PCR. HBx upregulates 456 genes and downregulates 843 genes, including programmed cell death 4 (PDCD4). PDCD4 was downregulated in clinical HCC specimens and the downregulation of PDCD4 in HCC is correlated with HBx. Furthermore, overexpression experiments in HCC cells proved that PDCD4 has strong tumor-suppressive effects both in vitro and in vivo, and may induce cell apoptosis to suppress the development of HCC. HBx induces expression of DNA methyltransferases (DNMTs), but failed to change the methylation status of the PDCD4 promoter. HBx downregulates PDCD4 expression at least partially through miR-21. Taken together, this study reported for the first time that HBx downregulates PDCD4 and upregulates miR-21 expression. The overexpression of PDCD4 could suppress tumorigenicity. The deregulation of PDCD4 by HBx through miR-21 represents a potential novel mechanism of the downregulation of PDCD4 in HBV-related HCC and provides new insights into HCC development.

BackgroundDNA-methyltransferase (DNMT)-3A plays an important role in the development of embryogenesis and the generation of aberrant methylation in carcinogenesis. The aim of this study was to investigate the role of a DNMT3A promoter genetic variant on its transcriptional activity and to evaluate the association between DNMT3A gene polymorphism and the susceptibility to gastric cancer (GC) and oesophagus carcinoma (EC) in the Chinese population.MethodsWe selected one of the single nucleotide polymorphisms (SNPs) -448A>G in the DNMT3A promoter region and evaluated its effect on activity using a luciferase assay. -448A>G polymorphisms of DNMT3A were determined by polymerase chain reaction/restriction fragment length polymorphism and confirmed by sequencing. The distribution of -448A>G polymorphisms was detected in 208 GC patients and 346 healthy controls matched for age and gender. The distribution of -448A>G polymorphisms was also detected in 96 EC patients and matched 241 healthy controls. The association of -448A>G polymorphisms of DNMT3A and the risk of GC and EC was evaluated by stratified analysis according to the patient's age and gender.ResultsIn a promoter assay, carriage of the -448 A allele showed a significantly higher promoter activity (> two fold) compared with the -448G allele (P < 0.001). The allele frequency of -448A among GC patients and controls was 32.9% versus 19.9%, respectively. Overall, we found that, compared with GG carriers, the DNMT3A -448AA homozygotes has a > six fold increased risk of GC. Stratification analysis showed that AA homozygotes have a more profound risk in the subgroups of individuals at the age range ≤ 60 years in GC. However, individuals with -448AG and -448AA were not statistically significantly associated with an increased risk of EC compared with those carried the -448GG genotype.ConclusionsThe DNMT3A -448A>G polymorphism is a novel functional SNP and contributes to its genetic susceptibility to GC. -448A>G can be used as a stratification marker to predict an individual's susceptibility to GC, especially in the subgroups of individuals at the age range ≤ 60 years. However, the relative distribution of -448A>G in EC can not be used as a prediction marker in order to evaluate an individual's susceptibility to EC.

DNA methyltransferase 3B (DNMT3B) mediates gene silencing via epigenetic mechanisms during hepatocellular carcinoma (HCC) progression. We aimed to identify novel targets of DNMT3B and their potential regulatory mechanisms in HCC. Metastasis suppressor 1 (MTSS1) was one of the DNMT3B targets and selected for further study. DNMT3B overexpression was detected in 81.25% of clinical HCC specimens and was negatively associated with MTSS1 in HCC cells and clinical samples. The underlying mechanism by which DNMT3B silences MTSS1 was studied using a combination of methylation-specific polymerase chain reaction (PCR) and bisulfite genome sequencing, chromatin immunoprecipitation-PCR and luciferase reporter assays. We found that the MTSS1 promoter region was sparsely methylated, and the methylation inhibitors failed to abolish DNMT3B-mediated MTSS1 silencing. DNMT3B protein bound directly to the 5 0 -flanking region (À865/À645) of the MTSS1 gene to inhibit its transcription. The functional role of MTSS1 was investigated using in vitro and in vivo tumorigenicity assays. As a result, MTSS1 exerted tumor suppressor effects and arrested cells in the G2/M phase, but not the G1/S phase of the cell cycle when it was depleted or overexpressed in HCC cells. Taken together, MTSS1, a novel target of DNMT3B, is repressed by DNMT3B via a DNA methylation-independent mechanism. MTSS1 was further characterized as a novel tumor suppressor gene in HCC. These findings highlight how DNMT3B regulates MTSS1, and such data may be useful for the development of new treatment options for HCC.