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.

Cannabinoids and monoaminergic system: implications for learning and memory.

Cannabinoids and the endocannabinoid system (ECS) have been intensively studied for their neuroregulatory roles in the central nervous system (CNS), especially in regulating learning and memory. However, many experimental and clinical studies obtained conflicting results indicating a complex network of interaction underlying the regulation of learning and memory by different cannabinoids and the ECS. The ECS influences neuronal synaptic communications, and therefore may exert different regulation via their different impact on other neurotransmitters. The monoaminergic system includes a variety of neurotransmitters, such as dopamine, norepinephrine, and serotonin, which play important roles in regulating mood, cognition, and reward. The interaction among cannabinoids, ECS and the monoaminergic system has drawn particular attention, especially their contributions to learning and memory. In this review, we summarized the current understanding of how cannabinoids, ECS and the monoaminergic system contribute to the process of learning and memory, and discussed the influences of monoaminergic neurotransmission by cannabinoids and ECS during this process.

Estimating corrosion induced thickness loss in Q690E high-strength steel using multimodal ultrasonic guided waves.

The estimation of corrosion induced thickness loss is critical for evaluating the remaining strength of high-strength steel (HSS) structures, particularly due to their emerging applications in ocean platforms and coastal bridges. In this study, an ultrasonic approach based on multimodal guide waves is proposed to identify thickness loss induced by electrical accelerated corrosion (EAC) in Q690E HSS samples. Both pitting corrosion and uniform corrosion were observed in the samples during the EAC testing. The average thickness loss due to corrosion in a plate-like structure can be correlated with the velocity of certain guided wave modes according to their dispersion characteristics. However, in practice, when the frequency-thickness product exceeds 1.5MHzmm, it becomes difficult to separate a single mode of guided wave. Hence, this paper addresses the use of multimodal guided waves and proposes a stretching factor that could describe the averaged velocity from different guided wave modes. This stretching factor is found to be linearly correlated to the averaged thickness loss from an analytical approach and validated by experiments. The influence of surface roughness due to pitting is found to be negligible due to the large wavelengths of guided waves. This method provides a simple and effective alternative to estimate the average thickness loss due to corrosion damage in HSS structures.

Online monitoring of fatigue damage in welded joints using diffuse ultrasound.

Fatigue damage is a common cause of failure in welded structures, and it is often difficult to detect it in the early stage. While ultrasonic-based methods can effectively monitor crack propagation, it remains a significant challenge to indicate the initiation of cracks. In this study, a novel method is proposed to monitor the diffuse ultrasonic field affected by ratcheting strain and microcracks formed in welded joints during fatigue degradation. The energy density in the diffuse ultrasonic signal is computed and correlated with different fatigue cycles, allowing for online monitoring of fatigue damage in welded joints. Six butt and cross-welded joints were studied under different fatigue conditions, and digital image correlation (DIC) technology was used for comparison throughout the fatigue tests. The results indicate that the correlation coefficient of the energy density in diffuse ultrasound exhibits a significant decreasing trend when crack initiation occurs, providing a unique signal to indicate crack initiation in welded joints. This signal may appear earlier than that from ratcheting strain monitored by DIC due to ultrasound's sensitivity to internal damages.

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.

Ballistic Thermal Transport at Sub-10 nm Laser-Induced Hot Spots in GaN Crystal.

Ballistic thermal transport at nanoscale hotspots will greatly reduce the performance of a Gallium nitride (GaN) device when its characteristic length reaches the nanometer scale. In this work, the authors develop a tip-enhanced Raman thermometry approach to study ballistic thermal transport within the range of 10 nm in GaN, simultaneously achieving laser heating and measuring the local temperature. The Raman results show that the temperature increase from an Au-coated tip-focused hotspot up to two times higher (40 K) than that in a bare tip-focused region (20 K). To further investigate the possible mechanisms behind this temperature difference, the authors perform electromagnetic simulations to generate a highly focused heating field, and observe a highly localized optical penetration, within a range of 10 nm. The phonon mean free path (MFP) of the GaN substrate can thus be determined by comparing the numerical simulation results with the experimentally measured temperature increase which is in good agreement with the average MFP weighted by the mode-specific thermal conductivity, as calculated from first-principles simulations. The results demonstrate that the phonon MFP of a material can be rapidly predicted through a combination of experiments and simulations, which can find wide application in the thermal management of GaN-based electronics.

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.

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.

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.

Characterization of phonon thermal transport of Ti3C2TxMXene thin film.

Two-dimensional MXene materials with high electrotonic conductivity, good chemical stability, and unique laminar structure show great potential in the field of electrochemistry. In contrast to the widely concerned electrical properties, studies on the thermal properties of MXene materials are very limited. This paper presents a comprehensive analysis of the thermal properties of Ti3C2TxMXene thin film. Thermal diffusivity and thermal conductivity of Ti3C2Txfilms are characterized by the transient electro-thermal technique. The experimental results show a 16% enhancement in thermal conductivity when the temperature is increased from 307 K to 352 K. The phonon transport contributes substantially to thermal conductivity compared with electron transport. Molecular dynamic simulation is employed to further investigate the role of phonon thermal transport of Ti3C2layer. It is found that the combined effect of specific heat capacity, stacking structure and internal stress states is responsible for the thermal transport performance of Ti3C2TxMXene thin film.

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.

HMGB1 downregulation in retinal pigment epithelial cells protects against diabetic retinopathy through the autophagy-lysosome pathway.

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus and currently one of the major causes of blindness. Several previous studies have demonstrated that autophagy, which is regulated by HMGB1 (high mobility group box 1), is involved in DR development. However, the role of autophagy in DR is quite complicated in that it promotes pericyte survival in early DR, whereas excessive autophagy causes excess stress and leads to necrosis. Therefore, this study aimed to investigate the relationship between HMGB1, the macroautophagy/autophagy-lysosome pathway, and DR, as well as their underlying molecular mechanisms. In brief, the relationship between high glucose (HG) and the autophagy-lysosome pathway was examined in retinal pigment epithelial (RPE) cells. The relationship was studied by detecting classical autophagic features, and siRNAs targeting HMGB1 and pharmacological regulators were used to explore the role of the autophagy-lysosome pathway in DR development. The results demonstrated that HG inhibited autophagy and diminished the degradative capacity of autophagy due to lysosome membrane permeabilization (LMP). In addition, HMGB1 was found to be involved in LMP via the CTSB (cathepsin B)-dependent pathway, but not the CTSL (cathepsin L)-dependent pathway. Knockdown of HMGB1 expression rescued LMP, restored the degradative capacity of autophagy, decreased the expression of inflammatory factors and VEGF (vascular endothelial growth factor), and protected against apoptosis in RPE cells in the early stages of DR.

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.

The fate of anaerobic syntrophy in anaerobic digestion facing propionate and acetate accumulation.

How the acetate and propionate accumulation impact anaerobic syntrophy during methane formation is not well understood. To investigate such effect, continuous acetate (35 g/L), propionate (11.25 g/L) and bicarbonate (30 g/L) supplementation were used during mesophilic anaerobic digestion. The high throughput sequencing (16S rRNA and mcrA), Real-Time quantitative PCR, and stable carbon isotope fingerprinting were applied to investigate the structure and activity of microbial community members. The results demonstrated that the abundance of syntrophic acetate oxidizing bacteria exhibited a gradual decrease coupled with heavier stable carbon isotopic signature of methane (δ 13CH4) in the three reagents impacted reactors. The increased acetate and propionate concentrations exerted negative influence on biogas production but the relatively stable hydrogenotrophic methanogens together with syntrophic acetate/propionate oxidizing bacteria kept the stable methane formation facing acetate and propionate accumulation. The functional genes copy number of the hydrogenotrophic Methanocellaceae and Methanomicrobiaceae correlated significantly with δ 13CH4 (R2 > 0.74), but only the abundance of Methanocellaceae fitted well with δ 13CH4 (p < 0.05). The δ 13CH4 signatures can predict methanogenesis, as it directly reflects the main methanogenic pathway; yet, further investigation of isotope fractionation in acetate/propionate coupled with δ 13CH4 is needed. Collectively, these results provide deep insight into anaerobic syntrophy and reveal changes of synergistic relationships, both of which may contribute to the stability of biogas reactors.

Extensive germline genome engineering in pigs.

The clinical applicability of porcine xenotransplantation-a long-investigated alternative to the scarce availability of human organs for patients with organ failure-is limited by molecular incompatibilities between the immune systems of pigs and humans as well as by the risk of transmitting porcine endogenous retroviruses (PERVs). We recently showed the production of pigs with genomically inactivated PERVs. Here, using a combination of CRISPR-Cas9 and transposon technologies, we show that pigs with all PERVs inactivated can also be genetically engineered to eliminate three xenoantigens and to express nine human transgenes that enhance the pigs' immunological compatibility and blood-coagulation compatibility with humans. The engineered pigs exhibit normal physiology, fertility and germline transmission of the 13 genes and 42 alleles edited. Using in vitro assays, we show that cells from the engineered pigs are resistant to human humoral rejection, cell-mediated damage and pathogenesis associated with dysregulated coagulation. The extensive genome engineering of pigs for greater compatibility with the human immune system may eventually enable safe and effective porcine xenotransplantation.

Distinguishing Optical and Acoustic Phonon Temperatures and Their Energy Coupling Factor under Photon Excitation in nm 2D Materials.

Under photon excitation, 2D materials experience cascading energy transfer from electrons to optical phonons (OPs) and acoustic phonons (APs). Despite few modeling works, it remains a long-history open problem to distinguish the OP and AP temperatures, not to mention characterizing their energy coupling factor (G). Here, the temperatures of longitudinal/transverse optical (LO/TO) phonons, flexural optical (ZO) phonons, and APs are distinguished by constructing steady and nanosecond (ns) interphonon branch energy transport states and simultaneously probing them using nanosecond energy transport state-resolved Raman spectroscopy. ΔT OP -AP is measured to take more than 30% of the Raman-probed temperature rise. A breakthrough is made on measuring the intrinsic in-plane thermal conductivity of suspended nm MoS2 and MoSe2 by completely excluding the interphonon cascading energy transfer effect, rewriting the Raman-based thermal conductivity measurement of 2D materials. G OP↔AP for MoS2, MoSe2, and graphene paper (GP) are characterized. For MoS2 and MoSe2, G OP↔AP is in the order of 1015 and 1014 W m-3 K-1 and G ZO↔AP is much smaller than G LO/TO↔AP. Under ns laser excitation, G OP↔AP is significantly increased, probably due to the reduced phonon scattering time by the significantly increased hot carrier population. For GP, G LO/TO↔AP is 0.549 × 1016 W m-3 K-1, agreeing well with the value of 0.41 × 1016 W m-3 K-1 by first-principles modeling.

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.

Effect of temperature on Raman intensity of nm-thick WS2: combined effects of resonance Raman, optical properties, and interface optical interference.

Temperature dependent Raman intensity of 2D materials features very rich information about the material's electronic structure, optical properties, and nm-level interface spacing. To date, there still lacks rigorous consideration of the combined effects. This renders the Raman intensity information less valuable in material studies. In this work, the Raman intensity of four supported multilayered WS2 samples are studied from 77 K to 757 K under 532 nm laser excitation. Resonance Raman scattering is observed, and we are able to evaluate the excitonic transition energy of B exciton and its broadening parameters. However, the resonance Raman effects cannot explain the Raman intensity variation in the high temperature range (room temperature to 757 K). The thermal expansion mismatch between WS2 and Si substrate at high temperatures (room temperature to 757 K) make the optical interference effects very strong and enhances the Raman intensity significantly. This interference effect is studied in detail by rigorously calculating and considering the thermal expansion of samples, the interface spacing change, and the optical indices change with temperature. Considering all of the above factors, it is concluded that the temperature dependent Raman intensity of the WS2 samples cannot be solely interpreted by its resonance behavior. The interface optical interference impacts the Raman intensity more significantly than the change of refractive indices with temperature.

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.

Critical fracture properties of puckered and buckled arsenenes by molecular dynamics simulations.

The pioneering prediction and successful synthesis of monolayer arsenene in recent years have promoted intensive studies on this novel two-dimensional (2D) material. Strain-engineered arsenene monolayer can change its geometric structures with tuned charge distribution, which paves the way for achieving novel electronic properties. The practical applications of the strain-driven topological state in arsenene strongly depend on its critical strain value. In this work, mechanical properties such as fracture strain, fracture strength and Young's modulus of two arsenene structures, i.e. buckled arsenene (b-arsenene) and puckered arsenene (p-arsenene), are comprehensively investigated under different modulators such as system dimension, chirality, temperature, strain rate and random surface defect. A maximum fracture strain reduction of 41.7% from 0.24 to 0.14 is observed in armchair b-arsenene when the temperature increases from 100 to 500 K. The most significant impact factor on the mechanical properties of arseneneis found to be surface defects. A maximum fracture strength reduction of 85.7% is predicted in the armchair b-arsenene when the defect ratio increases from 0 to 5%. On the other hand, the strain rate has a negligible effect on the mechanical properties. Our results provide fundamental knowledge on the critical fracture properties of arsenene.