RNA m6A dynamic modification mediated by nucleus-localized FTO is involved in follicular reserve.

In eukaryotic organisms, the most common internal modification of messenger RNA (mRNA) is N6-methyladenosine (m6A). This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers. The fat-mass and obesity-associated protein (FTO) catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes. Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles, with an inverse relationship observed for m6A levels and nuclear-localized FTO expression. Application of Fto small interfering RNA (siRNA) altered the expression of genes related to cell proliferation, hormone regulation, and cell chemotaxis, and affected RNA alternative splicing. Overexpression of the full-length Fto gene led to changes in m6A levels, alternative splicing of Cdk5, cell proliferation, cell cycle progression, and proportion of primordial follicles. Conversely, overexpression of Fto lacking a nuclear localization signal (NLS) did not significantly alter m6A levels or primordial follicle assembly. These findings suggest that FTO, localized in the nucleus but not in the cytoplasm, regulates RNA m6A demethylation and plays a role in cell proliferation, cell cycle progression, and primordial follicle assembly. These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

Ultraflexible Monolithic Three-Dimensional Static Random Access Memory.

Flexible static random access memory (SRAM) plays an important role in flexible electronics and systems. However, achieving SRAM with a small footprint, high flexibility, and high thermal stability has always been a big challenge. In this work, an ultraflexible six-transistor SRAM with high integration density is realized based on a monolithic three-dimensional (M3D) design. In this design, vertical stacked n-type indium gallium zinc oxide thin film transistors and p-type carbon nanotube transistors share common gate and drain electrodes, respectively, saving interlayer vias used in traditional M3D designs. This compact architecture reduces the footprint of the SRAM cell from a six-transistor to a four-transistor area, saving 33% of the area, and significantly enables the SRAM to have the highest flexibility among the reported ones, withstanding a harsh deforming process (6000 cycles of bending at a radius of 500 µm) without performance degradation. Moreover, this design facilitates the thermal stability of the SRAM under high temperature (333 K). It also exhibits great static and dynamic performance, with the highest normalized hold noise margin of 73.6%, a maximum gain of 151.2, and a minimum static power consumption of 3.15 µW in hold operation among the reported flexible SRAMs. This demonstration provides possibilities for SRAMs to be used in advanced wearable system applications.

Maternal tamoxifen exposure leads to abnormal primordial follicle assembly.

Tamoxifen (TAM) is an accredited drug used for treatment and prevention of breast cancer. Due to the long-term taking and the trend for women to delay childbearing, inadvertent conception occasionally occurs during TAM treatment. To explore the effects of TAM on a fetus, pregnant mice at gestation day 16.5 were orally administrated with different concentrations of TAM. Molecular biology techniques were used to analyze the effects of TAM on primordial follicle assembly of female offspring and the mechanism. It was found that maternal TAM exposure affected primordial follicle assembly and damaged the ovarian reserve in 3 dpp offspring. Up to 21 dpp, the follicular development had not recovered, with significantly decreased antral follicles and decreased total follicle number after maternal TAM exposure. Cell proliferation was significantly inhibited; however, the cell apoptosis was induced by maternal TAM exposure. Epigenetic regulation was also involved in the process of TAM induced abnormal primordial follicle assembly. The changed levels of H3K4me3, H3K9me3, and H3K27me3 presented the function of histone methylation in the regulation of the effects of maternal TAM exposure on the reproduction of female offspring. Moreover, the changed level of RNA m6A modification and the changed expression of genes related to transmethylation and demethylation proved the role of m6A in the process. Maternal TAM exposure led to abnormal primordial follicle assembly and follicular development by affecting cell proliferation, cell apoptosis, and epigenetics.

Performance Enhancement and Bending Restoration for Flexible Amorphous Indium Gallium Zinc Oxide Thin-Film Transistors by Low-Temperature Supercritical Dehydration Treatment.

For high-performance and high-lifetime flexible and wearable electronic applications, a low-temperature posttreatment method is highly expected to enhance the device performance and repair the defects induced by the low-temperature fabrication process intrinsically. Particularly, if the method can repair the traces induced by the multiple cycles of bending or deforming, it would overcome current fatal obstacles and provide a vital solution to the rapid development of flexible electronics. In this work, we propose a method to apply low-temperature supercritical CO2 fluid with a dehydration function to improve or even restore the performance of flexible amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs). After the treatment, the a-IGZO TFT exhibits 3 times improvement drivability up to 0.24 µA/µm, a smaller subthreshold swing of 0.18 V dec-1, a smaller Vth of 0.25 V, and a larger Ion/Ioff ratio of 3.8 × 107. Additionally, the posttreated a-IGZO TFTs possess relatively good uniformity and reproducibility with an on-current standard deviation of 0.047 µA/µm, and the performance of the a-IGZO TFT after the treatment remains almost unchanged even after bending 2500 times at a bending radius of 5 mm. These characteristics are attributed to the improved quality of the channel and gate dielectric. It is worth noting that when this is applied to a flexible TFT-driven organic light-emitting diode lighting system, this treatment method can restore the performance of not only the TFT but also the lighting system, even after the system has been bent more than 600 times and has failed. To date, this is the first time that the bending-track erasing function of the supercritical fluid for flexible systems has been reported, which has the potential to prolong the lifetime of flexible electronics.

Ultra-high drivability, high-mobility, low-voltage and high-integration intrinsically stretchable transistors.

Realizing intrinsically stretchable transistors with high current drivability, high mobility, small feature size, low power and the potential for mass production is essential for advancing stretchable electronics a critical step forward. However, it is challenging to realize these requirements simultaneously due to the limitations of the existing fabrication technologies when integrating intrinsically stretchable materials into transistors. Here, we propose a removal-transfer-photolithography method (RTPM), combined with adopting poly(urea-urethane) (PUU) as a dielectric, to realize integratable intrinsically stretchable carbon nanotube thin-film transistors (IIS-CNT-TFTs). The realized IIS-CNT-TFTs achieve excellent electrical and mechanical properties simultaneously, showing high field-effect-mobility up to 221 cm2 V-1 s-1 and high current density up to 810 µA mm-1 at a low driving voltage of -1 V, which are both the highest values for intrinsically stretchable transistors today to the best of our knowledge. At the same time, the transistors can survive 2000 cycles of repeated stretching by 50%, indicating their promising applicability to stretchable circuits, displays, and wearable electronics. The achieved intrinsically stretchable thin-film transistors show higher electrical performance, higher stretching durability, and smaller feature size simultaneously compared with the state-of-the-art works, providing a novel solution to integratable intrinsically stretchable electronics. Besides, the proposed RTPM involves adopting removable sacrificial layers to protect the PDMS substrate and PUU dielectric during the photolithography and patterning steps, and finally removing the sacrificial layers to improve the electrical and mechanical performance. This method is generally applicable to further enhance the performance of the existing transistors and devices with a similar structure in soft electronics.

Universal DNA detection realized by peptide based carbon nanotube biosensors.

Although DNA recognition has been achieved using numerous biosensors with various sensing probes, the utilization of bio-interaction between DNA and biomolecules has seldom been reported in universal DNA detection. Peptides as natural molecules have the unique ability to bind to universal DNA and excellent selectivity for DNA after being functionalized with specific groups. In this work, we report a peptide based carbon nanotube (CNT) thin-film-transistor (TFT) biosensor, which can achieve sensitive sequence-independent DNA detection. In the presence of DNA, a significant increase of ΔIon could be observed within 5 minutes, which was considered to be due to the electrostatic adsorption between the DNA and peptide of opposite zeta potential. With the gradual increase of the concentration of DNA, the ΔIon signals agree with the Hill-Langmuir model (R 2 = 0.98), indicating a negatively cooperative interaction between the peptide and DNA (the Hill coefficient n < 1). Compared with the former reported universal DNA bio-detector and NanoDrop (a spectrometer from Thermo Scientific™), this unique peptide based CNT-DNA sensor demonstrated a broader sensing range from nearly 1.6 × 10-4 to 5 µmol L-1 and a much lower detection limit of approximately 0.88 µg L-1. For the quantification of cDNA from T47D cancer cells, this unique peptide based CNT sensor could achieve efficient cDNA detection. To the best of our knowledge, this is the first report on the utilization of a peptide as a sensing element in the design of CNT based DNA biosensors, which enables highly efficient universal DNA detection.

Di (2-ethylhexyl) Phthalate Exposure Impairs the microRNAs Expression Profile During Primordial Follicle Assembly.

This research was performed to estimate the potential effects of Di (2-ethylhexyl) phthalate (DEHP) on changes of ovarian miRNA expression profile during mouse primordial follicle assembly using miRNAs-seq analysis. The ovaries of newborn mice were collected and in vitro cultured with different concentration of DEHP for 72 h. Then they were prepared for miRNAs-seq analysis. The results indicated that DEHP exposure altered ovarian miRNA expression profile of newborn mice. Eighteen differentially expressed miRNAs were screened after 100 µM DEHP exposure. The target mRNAs of differentially expressed miRNAs were predicted and further analyzed through gene ontology (GO) enrichment analysis and pathway enrichment analysis. Our results showed that the differentially expressed miRNAs from DEHP exposure can regulate ovarian development by targeting mRNAs involved in MAPK, mTOR, FoxO signaling pathways. Three miRNAs of miR-32-5p, miR-19a-3p, and miR-141-3p were randomly selected from the differentially expressed miRNAs to quantify their expression level by miRNA qRT-PCR. The results of qRT-PCR and miRNA-seq were consistent. Considering one of its target gene PTEN of miR-19a-3p and the decreased level of pAKT and increased Bax/Bcl-2 under DEHP exposure, we speculated that the altered expression of miR-19a-3p by DEHP exposure affected mouse primordial follicle assembly via PI3K/AKT1/mTOR signaling pathway. Epigenetic changes are one of the most important targets of toxicant exposure. The effects of DEHP exposure on microRNA (one of the epigenetic regulators) expression profile were uncovered to enrich the research on relationship of epigenetics and toxicant exposure.