Efficient immune responses rely on the proper differentiation of CD8
T cells into effector and memory cells. Here, we show a critical requirement of N
-Methyladenosine (m
A) methyltransferase Mettl3 ...during CD8
T cell responses upon acute viral infection. Conditional deletion of Mettl3 in CD8
T cells impairs effector expansion and terminal differentiation in an m
A-dependent manner, subsequently affecting memory formation and the secondary response of CD8
T cells. Our combined RNA-seq and m
A-miCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional regulators. Remarkably, Mettl3 binds to the Tbx21 transcript and stabilizes it, promoting effector differentiation of CD8
T cells. Moreover, ectopic expression of T-bet partially restores the defects in CD8
T cell differentiation in the absence of Mettl3. Thus, our study highlights the role of Mettl3 in regulating multiple target genes in an m
A-dependent manner and underscores the importance of m
A modification during CD8
T cell response.
N
-methyladenosine (m
A) methyltransferase Mettl3 is involved in conventional T cell immunity; however, its role in innate immune cells remains largely unknown. Here, we show that Mettl3 ...intrinsically regulates invariant natural killer T (iNKT) cell development and function in an m
A-dependent manner. Conditional ablation of Mettl3 in CD4
CD8
double-positive (DP) thymocytes impairs iNKT cell proliferation, differentiation, and cytokine secretion, which synergistically causes defects in B16F10 melanoma resistance. Transcriptomic and epi-transcriptomic analyses reveal that Mettl3 deficiency disturbs the expression of iNKT cell-related genes with altered m
A modification. Strikingly, Mettl3 modulates the stability of the Creb1 transcript, which in turn controls the protein and phosphorylation levels of Creb1. Furthermore, conditional targeting of Creb1 in DP thymocytes results in similar phenotypes of iNKT cells lacking Mettl3. Importantly, ectopic expression of Creb1 largely rectifies such developmental defects in Mettl3-deficient iNKT cells. These findings reveal that the Mettl3-m
A-Creb1 axis plays critical roles in regulating iNKT cells at the post-transcriptional layer.
T follicular helper (T
) cells are specialized effector CD4
T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in T
cells is unknown. Here, we show ...conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N
-methyladenosine (m
A) modification) in CD4
T cells impairs T
differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important T
signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m
A-miCLIP-seq shows the 3' UTR of Tcf7 mRNA is subjected to METTL3-dependent m
A modification. Loss of METTL3 or mutation of the Tcf7 3' UTR m
A site results in accelerated decay of Tcf7 transcripts. Importantly, ectopic expression of TCF-1 (encoded by Tcf7) rectifies T
defects owing to METTL3 deficiency. Our findings indicate that METTL3 stabilizes Tcf7 transcripts via m
A modification to ensure activation of a T
transcriptional program, indicating a pivotal function of post-transcriptional regulation in promoting T
cell differentiation.
Recent breakthroughs in two-dimensional (2D) van der Waals ferroelectrics have been impressive, with a series of 2D ferroelectrics having been realized experimentally. The discovery of ferroelectric ...order in atom-thick layers not only is important for exploring the interplay between dimensionality and ferroelectric order but may also enable ultra-high-density memory, which has attracted significant interest. However, understanding of 2D ferroelectrics goes beyond simply their atomic-scale thickness. In this Perspective, I suggest possible innovations that may resolve a number of conventional issues and greatly transform the roles of ferroelectrics in nanoelectronics. The major obstacles in the commercialization of nanoelectronic devices based on current ferroelectrics involve their insulating and interfacial issues, which hinder their combination with semiconductors in nanocircuits and reduce their efficiency in data reading/writing. In comparison, the excellent semiconductor performance of many 2D ferroelectrics may enable computing-in-memory architectures or efficient ferroelectric photovoltaics. In addition, their clean van der Waals interfaces can greatly facilitate their integration into silicon chips, as well as the popularization of nondestructive data reading and indefatigable data writing. Two-dimensional ferroelectrics also give rise to new physics such as interlayer sliding ferroelectricity, Moiré ferroelectricity, switchable metallic ferroelectricity, and unconventional robust multiferroic couplings, which may provide high-speed energy-saving data writing and efficient data-reading strategies. The emerging 2D ferroelectric candidates for optimization will help resolve some current issues (e.g., weak vertical polarizations), and further exploitation of the aforementioned advantages may open a new era of nanoferroelectricity.
Vertical ferroelectricity in two-dimensional (2D) materials is desirable for high-density data storage without quantum tunneling or high power consumption/dissipation, which still remains elusive due ...to the surface-depolarizing field. Herein, we report the first-principles evidence of 2D vertical ferroelectricity induced by interlayer translation, which exists extensively in the graphitic bilayer of BN, AlN, ZnO, MoS2, GaSe, etc.; the bilayer of some 2D ferromagnets like MXene, VS2, and MoN2 can be even multiferroics with switchable magnetizations upon ferroelectric switching, rendering efficient reading and writing for high-density data storage. In particular, the electromechanical coupling between interlayer translation and potential can be used to drive the flow of electrons as nanogenerators for harvesting energy from human activities, ocean waves, mechanical vibration, etc. A ferroelectric superlattice with spatial varying potential can be formed in a bilayer Moire pattern upon a small twist or strain, making it possible to generate periodic n/p doped-domains and shape the periodicity of the potential energy landscape. Finally, some of their multilayer counterparts with wurtzite structures like a ZnO multilayer are revealed to exhibit another type of vertical ferroelectricity with greatly enhanced polarizations.
Near the 100th anniversary of the discovery of ferroelectricity, so-called sliding ferroelectricity has been proposed and confirmed recently in a series of experiments that have stimulated remarkable ...interest. Such ferroelectricity exists widely and exists only in two-dimensional (2D) van der Waals stacked layers, where the vertical electric polarization is switched by in-plane interlayer sliding. Reciprocally, interlayer sliding and the "ripplocation" domain wall can be driven by an external vertical electric field. The unique combination of intralayer stiffness and interlayer slipperiness of 2D van der Waals layers greatly facilitates such switching while still maintaining environmental and mechanical robustness at ambient conditions. In this perspective, we discuss the progress and future opportunities in this behavior. The origin of such ferroelectricity as well as a general rule for judging its existence are summarized, where the vertical stacking sequence is crucial for its formation. This discovery broadens 2D ferroelectrics from very few material candidates to most of the known 2D materials. Their low switching barriers enable high-speed data writing with low energy cost. Related physics like Moiré ferroelectricity, the ferroelectric nonlinear anomalous Hall effect, and multiferroic coupling are discussed. For 2D valleytronics, nontrivial band topology and superconductivity, their possible couplings with sliding ferroelectricity via certain stacking or Moiré ferroelectricity also deserve interest. We provide critical reviews on the current challenges in this emerging area.
Objective: Loin muscle area (LMA) is an important target trait of pig breeding. This study aimed to identify single nucleotide polymorphisms (SNPs) and genes associated with LMA in the ...Duroc×(Landrace×Yorkshire) crossbred pigs (DLY). Methods: A genome-wide association study was performed using the Illumina 50K chip to map the genetic marker and genes associated with LMA in 511 DLY pigs (255 boars and 256 sows). Results: After quality control, we detected 35,426 SNPs, including six SNPs significantly associated with LMA in pigs, with MARC0094338 and ASGA0072817 being the two key SNPs responsible for 1.77% and 2.48% of the phenotypic variance of LMA, respectively. Based on previous research, we determined two candidate genes (growth hormone receptor GHR and 3-oxoacid Co A-transferase 1 OXCT1) that are associated with fat deposition and muscle growth and found further additional genes (MYOCD, ARHGAP44, ELAC2, MAP2K4, FBXO4, FBLL1, RARS1, SLIT3, and RANK3) that are presumed to have an effect on LMA. Conclusion: This study contributes to the identification of the mutation that underlies quantitative trait loci associated with LMA and to future pig breeding programs based on marker-assisted selection. Further studies are needed to elucidate the role of the identified candidate genes in the physiological processes involved in LMA regulation.
Phosphorene and phosphorene analogues such as SnS and SnSe monolayers are promising nanoelectronic materials with desired bandgap, high carrier mobility, and anisotropic structures. Here, we show ...first-principles calculation evidence that these monolayers are potentially the long-sought two-dimensional (2D) materials that can combine electronic transistor characteristic with nonvolatile memory readable/writeable capability at ambient condition. Specifically, phosphorene is predicted to be a 2D intrinsic ferroelastic material with ultrahigh reversible strain, whereas SnS, SnSe, GeS, and GeSe monolayers are multiferroic with coupled ferroelectricity and ferroelasticity. Moreover, their low-switching barriers render room-temperature nonvolatile memory accessible, and their notable structural anisotropy enables ferroelastic or ferroelectric switching readily readable via electrical, thermal, optical, mechanical, or even spintronic detection upon the swapping of the zigzag and armchair direction. In addition, it is predicted that the GeS and GeSe monolayers as well as bulk SnS and SnSe can maintain their ferroelasticity and ferroelectricity (anti-ferroelectricity) beyond the room temperature, suggesting high potential for practical device application.
Atomically thin Bi2O2Se has been recently synthesized, and it possesses ultrahigh mobility (Nat. Nanotechnol. 2017, 12, 530; Nano Lett. 2017, 17, 3021). Herein, we show first-principles evidence that ...Bi2O2Se and a related class of bismuth oxychalcogenides, such as Bi2O2S and Bi2O2Te, not only are novel semiconductors with ultrahigh mobility but also possess previously unreported ferroelectricity/ferroelasticity. Such a unique combination of semiconducting with ferroelectric/ferroelastic properties enables bismuth oxychalcogenides to potentially meet a great challenge, that is, integration of room-temperature functional nonvolatile memories into future nanocircuits. Specifically, we predict that bulk Bi2O2S is both ferroelastic and antiferroelectric and that a thin film with odd number of layers can even be multiferroic with nonzero in-plane polarization, and this polarization can be switchable via ferroelasticity. Moreover, Bi2O2Te possesses intrinsic out-of-plane ferroelectricity, while Bi2O2Se possesses piezoelectricity and ferroelectricity upon an in-plane strain. The in-plane strain on Bi2O2Se can induce giant polarizations (56.1 μC/cm2 upon 4.1% strain) with the piezoelectric coefficient being about 35 times higher than that of MoS2 monolayer. The in-plane strain can also enhance the bandgap or even convert indirect to direct bandgap beyond a critical value. The good match among the lattice constants of bismuth oxychalcogenides is also desirable, rendering the epitaxial growth of heterostructure devices free of fabrication issues related to lattice mismatch, thereby allowing high-quality bismuth oxychalcogenide heterostructures tailored by design for a variety of applications.
All‐solid‐state battery with Li metal anode is a promising rechargeable battery technology with high energy density and improved safety. Currently, the application of Li metal anode is plagued by the ...failure at the interfaces between lithium metal and solid electrolyte (SE). However, little is known about the defects at Li–SE interfaces and their effects on Li cycling, impeding further improvement of Li metal anodes. Herein, by performing large‐scale atomistic modeling of Li metal interfaces with common SEs, we discover that lithium metal forms an interfacial defect layer of nanometer‐thin disordered lithium at the Li–SE interfaces. This interfacial defect Li layer is highly detrimental, leading to interfacial failure such as pore formation and contact loss during Li stripping. By systematically studying and comparing incoherent, coherent, and semi‐coherent Li–SE interfaces, we find that the interface with good lattice coherence has reduced Li defects at the interface and has suppressed interfacial failure during Li cycling. Our finding discovered the critical roles of atomistic lithium defects at interfaces for the interfacial failure of Li metal anode, and motivates future atomistic‐level interfacial engineering for Li metal anode in solid‐state batteries.
Large‐scale atomistic modeling studied the interfaces between lithium metal and solid electrolytes with a wide range of lattice mismatch, and discovered an interfacial disordered Li defect layer at the interfaces and their roles in leading to the interfacial failure during lithium cycling.
