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Base editors have substantial promise in basic research and as therapeutic agents for the correction of pathogenic mutations. The development of adenine transversion editors has posed a particular challenge. Here we report a class of base editors that enable efficient adenine transversion, including precise A•T-to-C•G editing. We found that a fusion of mouse alkyladenine DNA glycosylase (mAAG) with nickase Cas9 and deaminase TadA-8e catalyzed adenosine transversion in specific sequence contexts. Laboratory evolution of mAAG significantly increased A-to-C/T conversion efficiency up to 73% and expanded the targeting scope. Further engineering yielded adenine-to-cytosine base editors (ACBEs), including a high-accuracy ACBE-Q variant, that precisely install A-to-C transversions with minimal Cas9-independent off-targeting effects. ACBEs mediated high-efficiency installation or correction of five pathogenic mutations in mouse embryos and human cell lines. Founder mice showed 44–56% average A-to-C edits and allelic frequencies of up to 100%. Adenosine transversion editors substantially expand the capabilities and possible applications of base editing technology.

Due to ultrafast switching speed and high-frequency switching of silicon carbide (SiC) metal-oxide-semiconductor field-effect transistor (mosfets), crosstalk effect, high turn-on losses and electromagnetic interference are becoming constraints to the efficient and safe applications of SiC mosfets. The split-output structure has attracted widespread attention due to its advantages of overcoming the above constraints by integrating decoupling inductors. Thereby, it fully exploits the potential benefits of SiC mosfets. In this article, the effects of the split inductors on short-circuit characteristics of split-output power module are analyzed. An analytical model of the split-output power module is established to compare the electrical characteristics of the split inductors under normal operation and short-circuit faults. A dedicated short-circuit protection method is proposed based on the detection of the voltage pulse duration across the split inductors. The protection method is validated by hard switching fault and fault under load experiments. The results show that the short-circuit power device can be shut down when the short-circuit current is much lower than the continuous drain current. Besides, the short-circuit energy of the power device has the same order of magnitude as the dissipated energy under normal switching, which avoids degradation and even destruction of SiC mosfets under short-circuit faults.

In this article, a multiport network approach is proposed to analyze the forced oscillations issue for the multichips power module. First, experimental results indicate the presence of multiple resonance points caused by forced oscillations during the switching process of multichip power modules. Due to the complex distribution of parasitic parameters within the module, it is challenging to establish an accurate analytical model. Therefore, this article proposes a method based on multisoftware collaborative simulation to extract the corresponding impedance of different chip ports. In addition, the impact of bus parasitic inductance and chip capacitances on port impedance is obtained. Compared with the experimental result, the error of dominant frequency obtained by the proposed model is less than 3%. Furthermore, the sensitivity of the spatial near-field spectrum to bus voltage and load current is studied based on experimental results. Finally, the suppression methods for forced oscillations are proposed based on the aforementioned theoretical analysis from the perspectives of both chips and packaging. The effectiveness of proposed methods is verified through experimental results.

Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor that can develop on the lining of nerves and within the network of nerve fibers in different organs, and it is commonly found in the head and neck, limbs, and trunk. These tumors can occur in patients of any age. They most commonly occur in adults aged 20 to 50 years; however, fewer cases of this tumor in children have been reported. To date, no neonatal case of MPNST in the nasal cavity has been reported. Here, we report the case of a 4-day-old female newborn who presented with a nasal mass that re-enlarged after surgery and was diagnosed as MPNST of the nasal cavity on the basis of pathological results. This is the first report of MPNST in the nasal cavity of a neonate. Differential diagnosis and treatment of nasal masses have been proposed in the related literature.

Cytosine base editors (CBEs) efficiently generate precise C·G-to-T·A base conversions, but the activation-induced cytidine deaminase/apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (AID/APOBEC) protein family deaminase component induces considerable off-target effects and indels. To explore unnatural cytosine deaminases, we repurpose the adenine deaminase TadA-8e for cytosine conversion. The introduction of an N46L variant in TadA-8e eliminates its adenine deaminase activity and results in a TadA-8e-derived C-to-G base editor (Td-CGBE) capable of highly efficient and precise C·G-to-G·C editing. Through fusion with uracil glycosylase inhibitors and further introduction of additional variants, a series of Td-CBEs was obtained either with a high activity similar to that of BE4max or with higher precision compared to other reported accurate CBEs. Td-CGBE/Td-CBEs show very low indel effects and a background level of Cas9-dependent or Cas9-independent DNA/RNA off-target editing. Moreover, Td-CGBE/Td-CBEs are more efficient in generating accurate edits in homopolymeric cytosine sites in cells or mouse embryos, suggesting their accuracy and safety for gene therapy and other applications.

The pursuit of high performance in specific conditions motivated the grand development of synthetic methodologies for single-atom catalysts (SACs) in various research fields. In general, the existing methods for SACs could be simply classified into two main types—“bottom-up” and “top-down”. The former was extensively explored and well documented elsewhere, whereas the latter is just on the rise. As it is, there is currently a lack of systematic overview for the top-down synthetic strategies to SACs. In this review, the rising top-down strategies are summarized in detail, including various thermo- and electrochemistry-based methods as well as other new protocols, based on the difference of metal-support interactions and energy input required during the atomization of bulk or micro- or nanoscale metal precursors. The introduction of the top-down synthetic strategies herein is believed to not only help establish the complete available methodology for task-specific SACs, but also contribute to the in-depth insights into the deactivation and regeneration mechanism of spent, supported metal catalysts for potential industrial application.

Efficient thermal energy storage technologies based on phase change materials (PCMs) that are capable of reversibly harvesting tremendous thermal energy during the isothermal phase transition have recently received unprecedented attention and are booming explosively in the exploitation of state-of-the-art multifunctional composite PCMs. In this regard, the smart integration of versatile metal oxides into PCMs has made significant contributions. However, a comprehensive review associated with the smart utilization of multifunctional metal oxides in PCMs is lacking. Here, we systematically summarize recent advances concerning the smart utilization of multifunctional metal oxides in PCMs for thermal storage, thermal transfer, energy conversion, and advanced versatile applications. This review aims to provide in-depth insights into the interactive relationships between multifunctional metal oxides and PCMs, thus providing a guide for the target design of high-performance multifunctional composite PCMs. We also highlight the current challenges and possible future research directions.

Homeobox (HOX) transcript antisense RNA (HOTAIR), a long intergenic noncoding RNA (lincRNA), has been reported to play an oncogenic role in various cancers including small cell lung cancer (SCLC). However, it is not known whether HOTAIR can modulate chemoresistance in SCLC. The aim of this study is to investigate the roles of HOTAIR in chemoresistance of SCLC and its possible molecular mechanism. Knockdown of HOTAIR was carried out in SCLC multidrug-resistant cell lines (H69AR and H446AR) and the parental cell lines (H69 and H446) to assess its influence on chemoresistance. The results showed that downregulation of HOTAIR increased cell sensitivity to anticancer drugs through increasing cell apoptosis and cell cycle arrest, and suppressed tumor growth in vivo. Moreover, HOXA1 methylation increased in the resistant cells using bisulfite sequencing PCR. Depletion of HOTAIR reduced HOXA1 methylation by decreasing DNMT1 and DNMT3b expression. The interaction between HOTAIR and HOXA1 was validated by RNA immunoprecipitation. Taken together, our study suggested that HOTAIR mediates chemoresistance of SCLC by regulating HOXA1 methylation and could be utilized as a potential target for new adjuvant therapies against chemoresistance.

Homeobox (HOX) transcript antisense RNA (HOTAIR), a long intergenic noncoding RNA (lincRNA), has been reported to play an oncogenic role in various cancers including small cell lung cancer (SCLC). However, it is not known whether HOTAIR can modulate chemoresistance in SCLC. The aim of this study is to investigate the roles of HOTAIR in chemoresistance of SCLC and its possible molecular mechanism. Knockdown of HOTAIR was carried out in SCLC multidrug-resistant cell lines (H69AR and H446AR) and the parental cell lines (H69 and H446) to assess its influence on chemoresistance. The results showed that downregulation of HOTAIR increased cell sensitivity to anticancer drugs through increasing cell apoptosis and cell cycle arrest, and suppressed tumor growth in vivo. Moreover, HOXA1 methylation increased in the resistant cells using bisulfite sequencing PCR. Depletion of HOTAIR reduced HOXA1 methylation by decreasing DNMT1 and DNMT3b expression. The interaction between HOTAIR and HOXA1 was validated by RNA immunoprecipitation. Taken together, our study suggested that HOTAIR mediates chemoresistance of SCLC by regulating HOXA1 methylation and could be utilized as a potential target for new adjuvant therapies against chemoresistance.

A two-mode adjustable superresolving filter based on a birefringent filter is proposed. This kind of filter has superresolution in two modes of adjustment. One is rotation of the binary pupil filter on the optical axis of the system and the other is the tilt of the filter away from the pupil plane on axis parallel or perpendicular to the optical axis of the crystal. The filters act as complex amplitude filters in the former mode, and as pure phase filters in the latter. By analyzing two superresolving parameters, we obtain the optimal design parameters that ensure a large field of view, a large superresolving range, and a high setting accuracy. This kind of filter can provide more flexibility in practical applications.