Ginsenoside Rh4 prevents endothelial dysfunction as a novel AMPK activator.

BACKGROUND AND PURPOSE: The AMP-activated protein kinase (AMPK) signalling pathway is a desirable target for various cardiovascular diseases (CVD), while the involvement of AMPK-mediated specific downstream pathways and effective interventions in hyperlipidaemia-induced endothelial dysfunction remain largely unknown. Herein, we aim to identify an effective AMPK activator and to explore its efficacy and mechanism against endothelial dysfunction. EXPERIMENTAL APPROACH: Molecular docking technique was adopted to screen for the potent AMPK activator among 11 most common rare ginsenosides. In vivo, poloxamer 407 (P407) was used to induce acute hyperlipidaemia in C57BL/6J mice. In vitro, palmitic acid (PA) was used to induce lipid toxicity in HAEC cells. KEY RESULTS: We discovered the strongest binding of ginsenoside Rh4 to AMPKα1 and confirmed the action of Rh4 on AMPK activation. Rh4 effectively attenuated hyperlipidaemia-related endothelial injury and oxidative stress both in vivo and in vitro and restored cell viability, mitochondrial membrane potential and mitochondrial oxygen consumption rate in HAEC cells. Mechanistically, Rh4 bound to AMPKα1 and simultaneously up-regulated AKT/eNOS-mediated NO release, promoted PGC-1α-mediated mitochondrial biogenesis and inhibited P38 MAPK/NFκB-mediated inflammatory responses in both P407-treated mice and PA-treated HAEC cells. The AMPK inhibitor Compound C treatment completely abrogated the regulation of Rh4 on the above pathways and weakened the lowering effect of Rh4 on endothelial impairment markers, suggesting that the beneficial effects of Rh4 are AMPK dependent. CONCLUSION AND IMPLICATIONS: Rh4 may serve as a novel AMPK activator to protect against hyperlipidaemia-induced endothelial dysfunction, providing new insights into the prevention and treatment of endothelial injury-associated CVD.

Controllable synthesis of high-entropy alloys.

High-entropy alloys (HEAs) involving more than four elements, as emerging alloys, have brought about a paradigm shift in material design. The unprecedented compositional diversities and structural complexities of HEAs endow multidimensional exploration space and great potential for practical benefits, as well as a formidable challenge for synthesis. To further optimize performance and promote advanced applications, it is essential to synthesize HEAs with desired characteristics to satisfy the requirements in the application scenarios. The properties of HEAs are highly related to their chemical compositions, microstructure, and morphology. In this review, a comprehensive overview of the controllable synthesis of HEAs is provided, ranging from composition design to morphology control, structure construction, and surface/interface engineering. The fundamental parameters and advanced characterization related to HEAs are introduced. We also propose several critical directions for future development. This review can provide insight and an in-depth understanding of HEAs, accelerating the synthesis of the desired HEAs.

Synthesis of Ultrathin High-Entropy Oxides with Phase Controllability.

High-entropy oxides (HEOs) with an ultrathin geometric structure are especially expected to exhibit extraordinary performance in different fields. The phase structure is deemed as a key factor in determining the properties of HEOs, rendering their phase control synthesis tempting. However, the disparity in intrinsic phase structures and physicochemical properties of multiple components makes it challenging to form single-phase HEOs with the target phase. Herein, we proposed a self-lattice framework-guided strategy to realize the synthesis of ultrathin HEOs with desired phase structures, including rock-salt, spinel, perovskite, and fluorite phases. The participation of the Ga assistor was conducive to the formation of the high-entropy mixing state by decreasing the formation energy. The as-prepared ultrathin spinel HEOs were demonstrated to be an excellent catalyst with high activity and stability for the oxygen evolution reaction in water electrolysis. Our work injects new vitality into the synthesis of HEOs for advanced applications and undoubtedly expedites their phase engineering.

The Role of Nicotinamide Mononucleotide Supplementation in Psoriasis Treatment.

Psoriasis is one of several chronic inflammatory skin diseases with a high rate of recurrence, and its pathogenesis remains unclear. Nicotinamide mononucleotide (NMN), as an important precursor of nicotinamide adenine dinucleotide (NAD+), has been reported to be a promising agent in treating various diseases, its positive effects including those induced via its anti-inflammatory and antioxidant properties. For this reason, we have aimed to explore the possible role of NMN in the treatment of psoriasis. Psoriasis models were constructed with imiquimod (IMQ) stimulation for 5 days in vivo and with M5 treatment in keratinocyte cell lines in vitro. NMN treatment during the IMQ application period markedly attenuated excess epidermal proliferation, splenomegaly, and inflammatory responses. According to GEO databases, Sirtuin1 (SIRT1) levels significantly decreased in psoriasis patients' lesion tissues; this was also the case in the IMQ-treated mice, while NMN treatment reversed the SIRT1 decline in the mouse model. Moreover, NMN supplementation also improved the prognoses of the mice after IMQ stimulation, compared to the untreated group with elevated SIRT1 levels. In HEKa and HaCaT cells, the co-culturing of NMN and M5 significantly decreased the expression levels of proinflammation factors, the phosphorylation of NF-κB, stimulator of interferon genes (STING) levels, and reactive oxygen species levels. NMN treatment also recovered the decrease in mitochondrial membrane potential and respiration ability and reduced mtDNA in the cytoplasm, leading to the inhibition of autoimmune inflammation. The knockdown of SIRT1 in vitro eliminated the protective and therapeutic effects of NMN against M5. To conclude, our results indicate that NMN protects against IMQ-induced psoriatic inflammation, oxidative stress, and mitochondrial dysfunction by activating the SIRT1 pathway.

Nuclear Factor Erythroid 2 Related Factor 2 and Mitochondria Form a Mutually Regulating Circuit in the Prevention and Treatment of Metabolic Syndrome.

Significance: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. Recent Advances: Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. Nuclear factor erythroid 2 related factor 2 (Nrf2) is one of the important systems responding to oxidative stress and inflammation. As cells undergo stress, cysteines within Kelch-like ECH-associated protein 1 (Keap1) are oxidized or electrophilically modified, allowing Nrf2 to escape ubiquitination and be translocated from the cytoplasm to the nucleus, facilitating the initiation of the antioxidant transcriptional program. Meanwhile, a growing body of evidence points out a specific modulation of mitochondrial homeostasis by Nrf2. After nuclear translocation, Nrf2 activates downstream genes involved in various aspects of mitochondrial homeostasis, including mitochondrial biogenesis and dynamics, mitophagy, aerobic respiration, and energy metabolism. In turn, mitochondria reciprocally activate Nrf2 by releasing reactive oxygen species and regulating antioxidant enzymes. Critical Issues: In this review, we first summarize the interactions between Nrf2 and mitochondria in the modulation of oxidative stress and inflammation to ameliorate MetS, then propose that Nrf2 and mitochondria form a mutually regulating circuit critical to maintaining homeostasis during MetS. Future Directions: Targeting the Nrf2-mitochondrial circuit may be a promising strategy to ameliorate MetS, such as obesity, diabetes, and cardiovascular diseases.

Interlayer Biatomic Pair Bridging the van der Waals Gap for 100% Activation of 2D Layered Material.

2D layered materials are regarded as prospective catalyst candidates due to their advantageous atomic exposure ratio. Nevertheless, the predominant population of atoms residing on the basal plane with saturated coordination, exhibit inert behavior, while a mere fraction of atoms located at the periphery display reactivity. Here, a novel approach is reported to attain complete atom activation in 2D layered materials through the construction of an interlayer biatomic pair bridge. The atoms in question have been strategically optimized to achieve a highly favorable state for the adsorption of intermediates. This optimization results from the introduction of new gap states around the Fermi level. Moreover, the presence of the interlayer bridge facilitates the electron transfer across the van der Waals gap, thereby enhancing the reaction kinetics. The hydrogen evolution reaction exhibits an impressive ultrahigh current density of 2000 mA cm-2 at 397 mV, surpassing the pristine MoS2 by approximately two orders of magnitude (26 mA cm-2 at 397 mV). This study provides new insights for enhancing the efficacy of 2D layered catalysts.

Gallium-Based Liquid Metals in Rechargeable Batteries: From Properties to Applications.

Gallium-based (Ga-based) liquid metals have attracted considerable interest due to their low melting points, enabling them to feature both liquid properties and metallic properties at room temperature. In light of this, Ga-based liquid metals also possess excellent deformability, high electrical and thermal conductivity, superior metal affinity, and unique self-limited surface oxide, making them popular functional materials in energy storage. This provides a possibility to construct high-performance rechargeable batteries that are deformable, free of dendrite growth, and so on. This review primarily starts with the property of Ga-based liquid metal, and then focuses on the potential applications in rechargeable batteries by exploiting these advantages, aiming to construct the correlation between properties and structures. The glorious applications contain interface protection, self-healing electrode construction, thermal management, and flexible batteries. Finally, the opportunities and obstacles for the applications of liquid metal in batteries are presented.

Ultrathin Van der Waals Lanthanum Oxychloride Dielectric for 2D Field-Effect Transistors.

Downsizing silicon-based transistors can result in lower power consumption, faster speeds, and greater computational capacity, although it is accompanied by the appearance of short-channel effects. The integration of high-mobility 2D semiconductor channels with ultrathin high dielectric constant (high-κ) dielectric in transistors is expected to suppress the effect. Nevertheless, the absence of a high-κ dielectric layer featuring an atomically smooth surface devoid of dangling bonds poses a significant obstacle in the advancement of 2D electronics. Here, ultrathin van der Waals (vdW) lanthanum oxychloride (LaOCl) dielectrics are successfully synthesized by precisely controlling the growth kinetics. These dielectrics demonstrate an impressive high-κ value of 10.8 and exhibit a remarkable breakdown field strength (Ebd ) exceeding 10 MV cm-1 . Remarkably, the conventional molybdenum disulfide (MoS2 ) field-effect transistor (FET) featuring a dielectric made of LaOCl showcases an almost negligible hysteresis when compared to FETs employing alternative gate dielectrics. This can be attributed to the flawlessly formed vdW interface and excellent compatibility established between LaOCl and MoS2 . These findings will motivate the further exploration of rare-earth oxychlorides and the development of more-than-Moore nanoelectronic devices.

Cutting-Edge Research in Nanoscience and Nanotechnology: Celebrating the 130th Anniversary of Wuhan University.

Thanks to the fast-paced progress of microscopic theories and nanotechnologies, a tremendous world of fundamental science and applications has opened up at the nanoscale. Ranging from quantum physics to chemical and biological mechanisms and from device functionality to materials engineering, nanoresearch has become an essential part of various fields. As one of the top universities in China, Wuhan University (WHU) aims to promote cutting-edge nanoresearch in multiple disciplines by leveraging comprehensive academic programs established throughout 130 years of history. As visible in prestigious scientific journals such as ACS Nano, WHU has made impactful advancements in various frontiers, including nanophotonics, functional nanomaterials and devices, biomedical nanomaterials, nanochemistry, and environmental science. In light of these contributions, WHU will be committed to serving talents and scientists wholeheartedly, fully supporting international collaborations and continuously driving innovative research.

2D quasi-layered material with domino structure.

Interlayer coupling strength dichotomizes two-dimensional (2D) materials into layered and non-layered types. Traditionally, they can be regarded as atomic layers intrinsically linked via van der Waals (vdW) forces or covalent bonds, oriented orthogonally to their growth plane. In our work, we report a material system that differentiates from layered and non-layered materials, termed quasi-layered domino-structured (QLDS) materials, effectively bridging the gap between these two typical categories. Considering the skewed structure, the force orthogonal to the 2D QLDS-GaTe growth plane constitutes a synergistic blend of vdW forces and covalent bonds, with neither of them being perpendicular to the 2D growth plane. This unique amalgamation results in a force that surpasses that in layered materials, yet is weaker than that in non-layered materials. Therefore, the lattice constant contraction along this unique orientation can be as much as 7.7%, tantalizingly close to the theoretical prediction of 10.8%. Meanwhile, this feature endows remarkable anisotropy, second harmonic generation enhancement with a staggering susceptibility of 394.3 pm V-1. These findings endow further applications arranged in nonlinear optics, sensors, and catalysis.

Emerging Liquid Metal Catalysts.

Catalysts serve pivotal roles in facilitating the development of sustainable energy systems on a global scale. Liquid metal usually refers to metal that is liquid below 330 °C, also known as low melting point metal. Liquid metal has emerged as an intriguing catalyst due to its commendable electrical conductivity, favorable fluidity, solubility in metals, phase transition capabilities, and modifiable oxide surface, thereby presenting a plethora of prospects for diverse catalytic reactions. In this Perspective, we elucidate the four primary merits of liquid metal catalysts: resistance to coking, the ability to tune elemental composition, the potential for structural transformation, and the capacity to inhibit coalescence. In light of this, a comprehensive summary is presented on the research advancements pertaining to liquid metal in methane pyrolysis, alkane dehydrogenation, carbon dioxide reduction, alcohol oxidation, and various other catalytic reactions. Finally, the challenges and prospects of liquid metal catalysts are elucidated.

Atomic Manufacturing in Electrode Materials for High-Performance Batteries.

The advancement of electrode materials plays a pivotal role in enhancing the performance of energy storage devices, thereby meeting the escalating need for energy storage and aligning with the imperative of sustainable development. Atomic manufacturing enables the precise manipulation of the crystal structure at the atomic level, thereby facilitating the development of electrode materials with customized physicochemical properties and enhancing their performance. In this Perspective, we elaborate on how atomic manufacturing enhances the important properties of electrode materials. Finally, we anticipate the prospect of materials and fabrication methods for atomic manufacturing in the future. This Perspective provides a comprehensive understanding for atomic manufacturing in electrode materials.

Comparative Study of Hydroxytyrosol Acetate and Hydroxytyrosol in Activating Phase II Enzymes.

Nuclear factor E2-related factor 2 (Nrf2) is fundamental to the maintenance of redox homeostasis within cells via the regulation of a series of phase II antioxidant enzymes. The unique olive-derived phenolic compound hydroxytyrosol (HT) is recognized as an Nrf2 activator, but knowledge of the HT derivative hydroxytyrosol acetate (HTac) on Nrf2 activation remains limited. In this study, we observed that an HT pretreatment could protect the cell viability, mitochondrial membrane potential, and redox homeostasis of ARPE-19 cells against a t-butyl hydroperoxide challenge at 50 µM. HTac exhibited similar benefits at 10 µM, indicating a more effective antioxidative capacity compared with HT. HTac consistently and more efficiently activated the expression of Nrf2-regulated phase II enzymes than HT. PI3K/Akt was the key pathway accounting for the beneficial effects of HTac in ARPE-19 cells. A further RNA-Seq analysis revealed that in addition to the consistent upregulation of phase II enzymes, the cells presented distinct expression profiles after HTac and HT treatments. This indicated that HTac could trigger a diverse cellular response despite its similar molecular structure to HT. The evidence in this study suggests that Nrf2 activation is the major cellular activity shared by HTac and HT, and HTac is more efficient at activating the Nrf2 system. This supports its potential future employment in various disease management strategies.

Atomic Manufacturing of Advanced Nanomaterials.

The quest for cutting-edge materials and devices has necessitated elevated demands for manufacturing methodologies. Atomic manufacturing involves the meticulous design and fabrication of materials and devices at the atomic level, a process that has been facilitated by advancements in comprehending and manipulating atomic behavior. The attainment of atomic manufacturing is dependent on the capacity to precisely manipulate atoms, directing their reactions at will. In this review, five methodologies of atomic fabrication encompassing atomic manipulation, atomic programming, atomic epitaxy, atomic confinement, and atomic assembly are elucidated. Based on this, the utilization of atomic manufacturing in the most advanced domains including energy conversion, energy storage, quantum information technology, and optoelectronic devices is elucidated. Finally, the current challenges and outlook on the forthcoming advancement of atomic manufacturing are presented.

High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes.

Most of the single-nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to evaluate the regulatory activities of 5,987 noncoding SNPs associated with IR-relevant phenotypes. We identified 876 SNPs with biased allelic enhancer activity effects (baaSNPs) across 133 loci in three IR-relevant cell lines (HepG2, preadipocyte, and A673), which showed pervasive cell specificity and significant enrichment for cell-specific open chromatin regions or enhancer-indicative markers (H3K4me1, H3K27ac). Further functional characterization suggested several transcription factors (TFs) with preferential allelic binding to baaSNPs. We also incorporated multi-omics data to prioritize 102 candidate regulatory target genes for baaSNPs and revealed prevalent long-range regulatory effects and cell-specific IR-relevant biological functional enrichment on them. Specifically, we experimentally verified the distal regulatory mechanism at IRS1 locus, in which rs952227-A reinforces IRS1 expression by long-range chromatin interaction and preferential binding to the transcription factor HOXC6 to augment the enhancer activity. Finally, based on our STARR-seq screening data, we predicted the enhancer activity of 227,343 noncoding SNPs associated with IR-relevant phenotypes (fasting insulin adjusted for BMI, HDL cholesterol, and triglycerides) from the largest available GWAS summary statistics. We further provided an open resource (http://www.bigc.online/fnSNP-IR) for better understanding genetic regulatory mechanisms of IR-relevant phenotypes.

Assembly of mitochondrial succinate dehydrogenase in human health and disease.

Mitochondrial succinate dehydrogenase (SDH), also known as electron transport chain (ETC) Complex II, is the only enzyme complex engaged in both oxidative phosphorylation and the tricarboxylic acid (TCA) cycle. SDH has received increasing attention due to its crucial role in regulating mitochondrial metabolism and human health. Despite having the fewest subunits among the four ETC complexes, functional SDH is formed via a sequential and well-coordinated assembly of subunits. Along with the discovery of subunit-specific assembly factors, the dynamic involvement of the SDH assembly process in a broad range of diseases has been revealed. Recently, we reported that perturbation of SDH assembly in different tissues leads to interesting and distinct pathophysiological changes in mice, indicating a need to understand the intricate SDH assembly process in human health and diseases. Thus, in this review, we summarize recent findings on SDH pathogenesis with respect to disease and a focus on SDH assembly.

A Monolayer High-Entropy Layered Hydroxide Frame for Efficient Oxygen Evolution Reaction.

High-entropy materials with tailored geometric and elemental compositions provide a guideline for designing advanced electrocatalysts. Layered double hydroxides (LDHs) are the most efficient oxygen evolution reaction (OER) catalyst. However, due to the huge difference in ionic solubility product, an extremely strong alkali environment is necessary to prepare high-entropy layered hydroxides (HELHs), which results in an uncontrollable structure, poor stability, and scarce active sites. Here, a universal synthesis of monolayer HELH frame in a mild environment is presented, regardless of the solubility product limit. Mild reaction conditions allow this study to precisely control the fine structure and elemental composition of the final product. Consequently, the surface area of the HELHs is up to 380.5 m2  g-1 . The current density of 100 mA cm-2 is achieved in 1 m KOH at an overpotential of 259 mV, and, after 1000 h operation at the current density of 20 mA cm-2 , the catalytic performance shows no obvious deterioration. The high-entropy engineering and fine nanostructure control open opportunities to solve the problems of low intrinsic activity, very few active sites, instability, and low conductance during OER for LDH catalysts.

Liquid metal for high-entropy alloy nanoparticles synthesis.

High-entropy alloy nanoparticles (HEA-NPs) show great potential as functional materials1-3. However, thus far, the realized high-entropy alloys have been restricted to palettes of similar elements, which greatly hinders the material design, property optimization and mechanistic exploration for different applications4,5. Herein, we discovered that liquid metal endowing negative mixing enthalpy with other elements could provide a stable thermodynamic condition and act as a desirable dynamic mixing reservoir, thus realizing the synthesis of HEA-NPs with a diverse range of metal elements in mild reaction conditions. The involved elements have a wide range of atomic radii (1.24-1.97 Å) and melting points (303-3,683 K). We also realized the precisely fabricated structures of nanoparticles via mixing enthalpy tuning. Moreover, the real-time conversion process (that is, from liquid metal to crystalline HEA-NPs) is captured in situ, which confirmed a dynamic fission-fusion behaviour during the alloying process.

Curvature geometry in 2D materials.

The two-dimensional (2D) material family can be regarded as the extreme externalization form of the matter in the planar 2D space. These atomically thin materials have abundant curvature structures, which will significantly affect their atomic configurations and physicochemical properties. Curvature engineering offers a new tuning freedom beyond the thoroughly studied layer number, grain boundaries, stacking order, etc. The precise control of the curvature geometry in 2D materials can redefine this material family. Special attention will be given to this emerging field and highlight possible future directions. With the step-by-step achievement in understanding the curvature engineering effect in 2D materials and establishing reliable delicate curvature controlling strategies, a brand-new era of 2D materials research could be developed.

Room-Temperature Magnetism in 2D MnGa4 -H Induced by Hydrogen Insertion.

2D room-temperature magnetic materials are of great importance in future spintronic devices while only very few are reported. Herein, a plasma-enhanced chemical vapor deposition approach is exploited to construct the 2D room-temperature magnetic MnGa4 -H single crystal with a thickness down to 2.2 nm. The employment of H2 plasma makes hydrogen atoms can be easily inserted into the MnGa4 lattice to modulate the atomic distance and charge state, thereby ferrimagnetism can be achieved without destroying the structural configuration. The as-obtained 2D MnGa4 -H crystal is high-quality, air-stable, and thermo-stable, demonstrating robust and stable room-temperature magnetism with a high Curie temperature above 620 K. This work enriches the 2D room-temperature magnetic family and opens up the possibility for the development of spintronic devices based on 2D magnetic alloys.