Quantum transport of short-gate MOSFETs based on monolayer MoSi2N4.

The high carrier mobility, appropriate band gap and good environmental stability of two-dimensional (2D) MoSi2N4 enable it to be an appropriate channel material for transistors with excellent performance. Therefore, we predict the performance of double-gate (DG) metal-oxide-semiconductor field-effect transistors (MOSFETs) based on monolayer (ML) MoSi2N4 by ab initio quantum-transport calculations. The results show that the on-state current of the p-type device is remarkable when the gate length is greater than 4 nm, which can meet the high performance requirements of the International Technology Roadmap for Semiconductors (ITRS), 2013 version. Moreover, the gate length can be reduced to 3 nm when an underlap (UL) structure is employed in the MOSFET, and the sub-threshold swing, intrinsic delay time and power consumption also perform well. The calculation results reveal that ML MoSi2N4 will be a promising alternative for transistor channel materials in the post-silicon era.

C1q/TNF-related protein-9 promotes macrophage polarization and improves cardiac dysfunction after myocardial infarction.

The timely regulation of inflammatory M1 macrophage polarization toward regenerative M2 macrophages suggests the possibility of immunotherapy after myocardial infarction (MI). C1q/TNF-related protein-9 (CTRP9) has anti-inflammatory effects and can ameliorate heart function in mice after long-term myocardial infarction. The role of CTRP9 in macrophage polarization remains completely unclear. This study determined whether CTRP9 can preserve post-MI early cardiac function through the regulation of macrophage polarization. In the present study, an adenovirus-delivered CTRP9 supplement promoted macrophage polarization at Day 3 post MI and improved cardiac function at Day 7 post MI. Pretreatment with gCTRP9 promoted the M1 to M2 polarization transition and attenuated inflammation after lipopolysaccharide + interferon-γ stimulation; the effects were partly abrogated by the adenosine monophosphate kinase (AMPK) inhibitor compound C and were obviously reinforced by pyrrolidine dithiocarbamate, a nuclear factor-κB (NF-κB) inhibitor. Meanwhile, CTPR9 markedly reduced the expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF-κB p65 phosphorylation by promoting AMPK phosphorylation in vivo and in vitro. Moreover, the competitive binding of gCTRP9 and LPS to the myeloid differentiation protein 2 (MD2)/TLR4 complex was associated with direct binding to MD2, thereby inhibiting the downstream signaling molecule MyD88. Taken together, we demonstrated that CTRP9 improved post-MI early cardiac function, at least in part, by modulating M1/M2 macrophage polarization, largely via the TLR4/MD2/MyD88 and AMPK-NF-κB pathways.

Visible-ultraviolet dual-band photodetectors based on an all-inorganic CsPbCl3/p-GaN heterostructure.

All-inorganic metal halide perovskites (MHPs) have attracted increasing attention because of their high thermal stability and band gap tunability. Among them, CsPbCl3 is considered a promising semiconductor material for visible-ultraviolet dual-band photodetectors because of its excellent photoelectric properties and suitable band gap value. In this work, we fabricated a visible-ultraviolet dual-band photodetector based on a CsPbCl3/p-GaN heterojunction using the spin coating method. The formation of the heterojunction enables the device to exhibit obvious dual-band response behavior at positive and negative bias voltages. At the same time, the dark current of the device can be as low as 2.42 × 10-9 A, and the corresponding detection rate can reach 5.82 × 1010 Jones. In addition, through simulation calculations, it was found that the heterojunction has a type II energy band arrangement, and the heterojunction response band light absorption is significantly enhanced. The type II energy band arrangement will separate electron-hole pairs more effectively, which will help improve device performance. The successful implementation of visible-ultraviolet dual-band photodetectors based on a CsPbCl3/p-GaN heterojunction provides guidance for the application of all-inorganic MHPs in the field of multi-band photodetectors.

Methylation synthetic lethality: Exploiting selective drug targets for cancer therapy.

In cancer, synthetic lethality refers to the drug-induced inactivation of one gene and the inhibition of another in cancer cells by a drug, resulting in the death of only cancer cells; however, this effect is not present in normal cells, leading to targeted killing of cancer cells. Recent intensive epigenetic research has revealed that aberrant epigenetic changes are more frequently observed than gene mutations in certain cancers. Recently, numerous studies have reported various methylation synthetic lethal combinations involving DNA damage repair genes, metabolic pathway genes, and paralogs with significant results in cellular models, some of which have already entered clinical trials with promising results. This review systematically introduces the advantages of methylation synthetic lethality and describes the lethal mechanisms of methylation synthetic lethal combinations that have recently demonstrated success in cellular models. Furthermore, we discuss the future opportunities and challenges of methylation synthetic lethality in targeted anticancer therapies.

Broadband Photodetector for Ultraviolet to Visible Wavelengths Based on the BA2PbI4/GaN Heterostructure.

Two-dimensional (2D) organic-inorganic hybrid perovskites (OIPs) have exhibited ideal prospects for perovskite photodetectors (PDs) owing to their remarkable environmental stability, tunable band gap, and structural diversity. However, most perovskites face the great challenge of a narrow spectral response. Integrating 2D OIPs with a suitable wide band gap semiconductor gives opportunities to broaden the response spectra. Here, a photodetector based on the BA2PbI4/GaN heterostructure with a broadband photoresponse covering from the ultraviolet (UV) to visible band is designed. We demonstrate that the device is capable of detecting in the UV region by p-GaN being integrated with BA2PbI4. The morphology and material optical properties of BA2PbI4 are characterized by transmission electron microscopy (TEM) and photoluminescence (PL). Additionally, the current-voltage (I-V) characteristics and photoresponses of the BA2PbI4/GaN heterojunction photodetector are investigated. The response spectrum of the photodetector is broadened from the visible to UV region, exhibiting good rectifying behavior in the dark conditions and a broadband photoresponse from the UV to the visible region. Additionally, the energy band is used to analyze the current mechanism of the BA2PbI4/GaN heterojunction PD. This study is expected to provide a new insight of optoelectronic devices by integrating 2D OIPs such as BA2PbI4 and wide-band-gap semiconductors such as GaN to broaden the response spectra.

CTRP9 Ameliorates Atrial Inflammation, Fibrosis, and Vulnerability to Atrial Fibrillation in Post-Myocardial Infarction Rats.

Background Inflammation and fibrosis play an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). CTRP9 (C1q/tumor necrosis factor-related protein-9) as a secreted glycoprotein can reverse left ventricle remodeling post-MI, but its effects on MI-induced atrial inflammation, fibrosis, and associated AF are unknown. Methods and Results MI model rats received adenoviral supplementation of CTRP9 (Ad-CTRP9) by jugular-vein injection. Cardiac function, inflammatory, and fibrotic indexes and related signaling pathways, electrophysiological properties, and AF inducibility of atria in vivo and ex vivo were detected in 3 or 7 days after MI. shCTRP9 (short hairpin CTRP9) and shRNA were injected into rat and performed similar detection at day 5 or 10. Adverse atrial inflammation and fibrosis, cardiac dysfunction were induced in both MI and Ad-GFP (adenovirus-encoding green fluorescent protein)+MI rats. Systemic CTRP9 treatment improved cardiac dysfunction post-MI. CTRP9 markedly ameliorated macrophage infiltration and attenuated the inflammatory responses by downregulating interleukin-1ß and interleukin-6, and upregulating interleukin-10, in 3 days post-MI; depressed left atrial fibrosis by decreasing the expressions of collagen types I and III, α-SMA, and transforming growth factor ß1 in 7 days post-MI possibly through depressing the Toll-like receptor 4/nuclear factor-κB and Smad2/3 signaling pathways. Electrophysiologic recordings showed that increased AF inducibility and duration, and prolongation of interatrial conduction time induced by MI were attenuated by CTRP9; moreover, CTRP9 was negatively correlated with interleukin-1ß and AF duration. Downregulation of CTRP9 aggravated atrial inflammation, fibrosis, susceptibility of AF and prolonged interatrial conduction time, without affecting cardiac function. Conclusions CTRP9 is effective at attenuating atrial inflammation and fibrosis, possibly via its inhibitory effects on the Toll-like receptor 4/nuclear factor-κB and Smad2/3 signaling pathways, and may be an original upstream therapy for AF in early phase of MI.

C1q/TNF-related protein-9 attenuates retinal inflammation and protects blood-retinal barrier in db/db mice.

C1q/TNF-related protein-9(CTRP9) is an adipose cytokine, a closest adiponectin paralog, which has anti-inflammatory, antioxidant, vasodilation and anti-atherosclerosis effects. In addition, it can increase insulin sensitivity, decrease blood glucose level and inhibit the apoptosis of endothelial cells. However, it remains unclear whether CTRP9 has beneficial effects on diabetic retinopathy (DR). An adenoviral vector expressing CTRP9 was intravenously injected into db/db mice, aged 12 weeks, at day 15 post injection, and the process was repeated. The transfection efficiency of CTRP9 was assessed by enzyme linked immunosorbent assay. We used RT-PCR, immunofluorescence, and Western blot to determine proinflammatory cytokines, adhesion molecules and tight-junction proteins. The breakdown of blood-retinal barrier (BRB) was evaluated using Evans blue and retinal staining. CTRP9 suppresses the expression of interleukin-1 beta, tumor necrosis factor-alpha, monocyte chemotactic protein-1 and adhesion molecules in the retina of db/db mice. CTRP9 can balance the expression of pigment epithelium-derived factor and vascular endothelial growth factor. CTRP9 can also inhibit the activation of nuclear factor Kappa B in the retina of db/db mouse. In addition, CTRP9 can prevent the breakdown of BRB and downregulation of tight-junction proteins in the retina of db/db mice. Evans blue assay revealed the breakdown of BRB and vascular leakage in the retinas of diabetic mice. CTRP9 can both qualitatively and quantitatively alleviate the vascular leakage in the early stage of diabetic retinas. CTRP9 can inhibit the inflammation of diabetic retinopathy and protect blood-retinal barrier via decreasing proinflammatory cytokines and preventing the downregulation of tight-junction proteins.

Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells.

Bone mesenchymal stem cells (BMSCs) are currently considered the optimal stem cells for biological pacemaker cell transformation. The cardiac­specific transcription factor T­Box protein 18 (TBX18) is essential for sinoatrial node (SAN) formation, particularly formation of the head region that generates the electrical impulses that induce heart contraction. The present study aimed to confirm the effects of TBX18 on biological pacemaker differentiation of rat BMSCs. Flow cytometry was used to identify the surface markers of BMSCs, in order to acquire pure mesenchymal stem cells. Subsequently, BMSCs were transduced with TBX18 or green fluorescent protein adenovirus vectors. The effects of TBX18 were evaluated using SAN­specific makers including TBX18, α­actin, cardiac troponin I, hyperpolarization­activated cyclic nucleotide­gated channel 4 and connexin 43 by reverse transcription­quantitative polymerase chain reaction, western blotting and immunofluorescence. The findings demonstrated that direct conversion of BMSCs to biological pacemaker cells via TBX18 is a feasible method in the field of cardiology.