Melatonin Regulates Neuronal Synaptic Plasticity in the Supramammillary Nucleus and Attenuates Methamphetamine-Induced Conditioned Place Preference and Sensitization in Mice.

Methamphetamine (METH) is an addictive drug that threatens human health. The supramammillary nucleus (SuM) and its neural circuits play key roles in the regulation of spatial memory retrieval, and hippocampal contextual or social memory. Melatonin (MLT), a pineal hormone, can regulate hypothalamic-neurohypophysial activity. Our previous study showed that MLT attenuates METH-induced locomotor sensitization. However, whether MLT regulates SuM function and participates in METH-induced contextual memory retrieval remains unclear. Using a mouse model of METH-conditioned place preference (CPP) and sensitization, we found that METH activated c-Fos expression and elevated calcium (Ca²âº) levels in SuM neurons. Chemogenetic inhibition of SuM attenuates CPP and sensitization. Pretreatment with MLT decreased c-Fos expression and Ca2+ levels in the SuM and reversed METH-induced addictive behavior, effects that were blocked with the selective MT2 receptors antagonist 4P-PDOT and the MT1 receptors antagonist S26131. Furthermore, MLT reduced SuM synaptic plasticity, glutamate (Glu) release, and neuronal oscillations caused by METH, which were blocked by 4P-PDOT. In conclusion, our data revealed that MLT regulates neuronal synaptic plasticity in the SuM, likely through the MLT receptors (MTs), and plays a role in modulating METH-addictive behavior.

Molecular dynamics study on thermal conductance between a nanotip and a substrate under vertical forces and horizontal sliding.

The heat transfer between a nanotip and its substrate is extremely complex but is a key factor in determining the measurement accuracy in tip-assisted nanomanufacturing and thermometry. In this work, the heat transfer from the nanotip to the substrate during sliding is investigated using molecular dynamics simulations. Interfacial interaction and bond formation are analyzed during the sliding process. The results show that the increase of vertical force would greatly improve the interface thermal conductance between the nanotip and the substrate. It is found that more bonds are formed and there are larger contact areas at the interface. In addition, we found that the thermal conductivity of the nanotip is another obstacle for heat transfer between the tip and substrate and it is greatly limited by the nanotip diameter near contact which is close to or even smaller than the phonon mean free path. Meanwhile, the dynamic formation and breakage of the covalent bonds during the sliding could gradually smoothen the tip apex and enhance the thermal transport at the interface. This work provides guidance for the thermal design of a nanotip-substrate system for nanoscale thermal transport measurements.

RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation.

N(6)-methyladenosine (m(6)A) is the most prevalent and internal modification that occurs in the messenger RNAs (mRNA) of most eukaryotes, although its functional relevance remained a mystery for decades. This modification is installed by the m(6)A methylation "writers" and can be reversed by demethylases that serve as "erasers." In this review, we mainly summarize recent progress in the study of the m(6)A mRNA methylation machineries across eukaryotes and discuss their newly uncovered biological functions. The broad roles of m(6)A in regulating cell fates and embryonic development highlight the existence of another layer of epigenetic regulation at the RNA level, where mRNA is subjected to chemical modifications that affect protein expression.

Self-Modulation-Guided Growth of 2D Tellurides with Ultralow Thermal Conductivity.

Ultralow thermal conductivity materials have triggered much interest due to diverse applications in thermal insulation, thermal barrier coating, and especially thermoelectrics. Two dimensional (2D) indium tellurides with ultralow thermal conductivity provide a versatile platform for tailoring the heat transfer, exploring new candidates for thermoelectrics, and achieving miniature, lightweight, and highly integrated devices. Unfortunately, their nanostructure and structure-related heat transfer properties at a 2D scale are much less studied due to difficulties in material fabrication. The ionic character between interlayers and strong covalent bonds in 3D directions impede the anisotropic growth of indium telluride flakes; meanwhile, the low environmental stability and chemical reactivity of tellurium also limit the fabrication of high-quality tellurides, thus hindering the exploration of thermal transport properties. Here, a self-modulation-guided growth strategy to synthesize high-quality 2D In4 Te3 single crystals with ultralow thermal conductivity (0.47 W m-1  K-1 ) is developed. This strategy can also be extended to synthesize a series of highly crystallized metal tellurides, providing excellent candidates for further application in thermoelectrics.

A metabolic labeling method detects m6A transcriptome-wide at single base resolution.

Transcriptome-wide mapping of N6-methyladenosine (m6A) at base resolution remains an issue, impeding our understanding of m6A roles at the nucleotide level. Here, we report a metabolic labeling method to detect mRNA m6A transcriptome-wide at base resolution, called 'm6A-label-seq'. Human and mouse cells could be fed with a methionine analog, Se-allyl-L-selenohomocysteine, which substitutes the methyl group on the enzyme cofactor SAM with the allyl. Cellular RNAs could therefore be metabolically modified with N6-allyladenosine (a6A) at supposed m6A-generating adenosine sites. We pinpointed the mRNA a6A locations based on iodination-induced misincorporation at the opposite site in complementary DNA during reverse transcription. We identified a few thousand mRNA m6A sites in human HeLa, HEK293T and mouse H2.35 cells, carried out a parallel comparison of m6A-label-seq with available m6A sequencing methods, and validated selected sites by an orthogonal method. This method offers advantages in detecting clustered m6A sites and holds promise to locate nuclear nascent RNA m6A modifications.

Applications of machine learning in computational nanotechnology.

Machine learning (ML) has gained extensive attention in recent years due to its powerful data analysis capabilities. It has been successfully applied to many fields and helped the researchers to achieve several major theoretical and applied breakthroughs. Some of the notable applications in the field of computational nanotechnology are ML potentials, property prediction, and material discovery. This review summarizes the state-of-the-art research progress in these three fields. ML potentials bridge the efficiency versus accuracy gap between density functional calculations and classical molecular dynamics. For property predictions, ML provides a robust method that eliminates the need for repetitive calculations for different simulation setups. Material design and drug discovery assisted by ML greatly reduce the capital and time investment by orders of magnitude. In this perspective, several common ML potentials and ML models are first introduced. Using these state-of-the-art models, developments in property predictions and material discovery are overviewed. Finally, this paper was concluded with an outlook on future directions of data-driven research activities in computational nanotechnology.

Anisotropic thermal transport in twisted bilayer graphene.

Recently, twisted bilayer graphene (TBLG) has attracted enormous attention owing to its peculiar electronic properties. In this work, the anisotropic thermal conductivity of TBLG is comprehensively investigated. It is reported that interlayer twisting can be a practical approach for thermal transport regulation with high accuracy. A strong non-monotonic correlation between anisotropic thermal conductivity and twisting angles is revealed. Extensive phonon behavior analyses reveal the physical mechanism. The anisotropic thermal transport in TBLG is explained by the calculated phonon density of states (PDOS). Meanwhile, the phonon spectra and phonon relaxation times extracted from spectral energy density (SED) profiles explain the decreasing trend of thermal conductivity with increasing twisting angles. The increase in thermal conductivity is attributed to the combined effects of twist and anisotropy. The reported anisotropic thermal conductivity is important to the thermal modulation and our analyses provide a valuable complement to the phonon studies of TBLG.

Tuning thermal and electrical properties of MXenes via dehydration.

Recently, MXenes (a class of two-dimensional transition metal carbides) have attracted great attention in various applications such as humidity sensors, owing to their unique electrical and thermal properties. However, previous studies of MXenes mostly focus on their humidity-sensing characteristics such as the mechanical response, and only few reports on their electrical and thermal response are available. Herein, we present novel transient electrothermal experiments to demonstrate that a transition from a negative to a positive resistance-temperature relationship can take place when the MXene sample becomes fully dehydrated. This surprising and unusual phenomenon was elucidated through non-equilibrium molecular dynamics simulations and attributed to water absorption/desorption onto the chemically active MXene surface. A linear relationship was also found between electrical/thermal properties and environmental humidity, which could be related to water adsorption on the surface of the MXene sensor. We further decomposed the total measured thermal conductivity and found that phonons were the dominant thermal carriers in the MXene sample. The main breakthrough of this work is the discovery of the unusual resistance-temperature relationship, which should be applicable to the design of MXene-based sensors for various applications.

Full-spectrum thermal analysis in twisted bilayer graphene.

It has been recently reported that a magic angle, i.e. 1.1°, exists in twisted bilayer graphene which could lead to intrinsic unconventional superconductivity. Variations of the twisting angle between different graphene layers could lead to altered electronic band structures, which results in the peculiar superconductivity phenomenon. The effects of twisting angles on different properties of bilayer graphene need to be comprehensively investigated in order to fully understand its mechanism. In this work, classical molecular dynamics simulations are performed to calculate the interfacial thermal resistance (R) at twisting angles from 0° to 359°. Due to the symmetric structures of the honeycomb lattice, only angles from 0° to 60° are needed but the full spectrum is explored to generate the complete picture of R with θ. It was reported that the interfacial thermal resistance changes periodically with the twisting angle, with the smallest R values at every 60° starting from 0° and the largest values at every 60° starting from 30°. The phonon density of states and radial distribution functions are calculated to explain the predicted results. The effects of temperature and single- and bi-direction tensile strains on the calculated interfacial thermal resistance are also studied. The results in this work contribute to the fundamental understanding of the thermal properties in twisted bilayer graphene and provide reasonable guidelines to its applications in thermal management devices.

Hepatitis B virus-triggered PTEN/ß-catenin/c-Myc signaling enhances PD-L1 expression to promote immune evasion.

Hepatitis B virus (HBV) exploits multiple strategies to evade host immune surveillance. Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling plays a critical role in regulating T cell homeostasis. However, it remains largely unknown as to how HBV infection elevates PD-L1 expression in hepatocytes. A mouse model of HBV infection was established by hydrodynamic injection with a vector containing 1.3-fold overlength HBV genome (pHBV1.3) via the tail vein. Coculture experiments with HBV-expressing hepatoma cells and Jurkat T cells were established in vitro. We observed significant decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and increase in ß-catenin/PD-L1 expression in liver tissues from patients with chronic hepatitis B and mice subjected to pHBV1.3 hydrodynamic injection. Mechanistically, decrease in PTEN enhanced ß-catenin/c-Myc signaling and PD-L1 expression in HBV-expressing hepatoma cells, which in turn augmented PD-1 expression, lowered IL-2 secretion, and induced T cell apoptosis. However, ß-catenin disruption inhibited PTEN-mediated PD-L1 expression, which was accompanied by decreased PD-1 expression, and increased IL-2 production in T cells. Luciferase reporter assays revealed that c-Myc stimulated transcriptional activity of PD-L1. In addition, HBV X protein (HBx) and HBV polymerase (HBp) contributed to PTEN downregulation and ß-catenin/PD-L1 upregulation. Strikingly, PTEN overexpression in hepatocytes inhibited ß-catenin/PD-L1 signaling and promoted HBV clearance in vivo. Our findings suggest that HBV-triggered PTEN/ß-catenin/c-Myc signaling via HBx and HBp enhances PD-L1 expression, leading to inhibition of T cell response, and promotes HBV immune evasion.NEW & NOTEWORTHY This study demonstrates that during HBV infection, HBV can increase PD-L1 expression via PTEN/ß-catenin/c-Myc signaling pathway, which in turn inhibits T cell response and ultimately promotes HBV immune evasion. Targeting this signaling pathway is a potential strategy for immunotherapy of chronic hepatitis B.