Imaging tunable Luttinger liquid systems in van der Waals heterostructures.

One-dimensional (1D) interacting electrons are often described as a Luttinger liquid1-4 having properties that are intrinsically different from those of Fermi liquids in higher dimensions5,6. In materials systems, 1D electrons exhibit exotic quantum phenomena that can be tuned by both intra- and inter-1D-chain electronic interactions, but their experimental characterization can be challenging. Here we demonstrate that layer-stacking domain walls (DWs) in van der Waals heterostructures form a broadly tunable Luttinger liquid system, including both isolated and coupled arrays. We have imaged the evolution of DW Luttinger liquids under different interaction regimes tuned by electron density using scanning tunnelling microscopy. Single DWs at low carrier density are highly susceptible to Wigner crystallization consistent with a spin-incoherent Luttinger liquid, whereas at intermediate densities dimerized Wigner crystals form because of an enhanced magneto-elastic coupling. Periodic arrays of DWs exhibit an interplay between intra- and inter-chain interactions that gives rise to new quantum phases. At low electron densities, inter-chain interactions are dominant and induce a 2D electron crystal composed of phased-locked 1D Wigner crystal in a staggered configuration. Increased electron density causes intra-chain fluctuation potentials to dominate, leading to an electronic smectic liquid crystal phase in which electrons are ordered with algebraical correlation decay along the chain direction but disordered between chains. Our work shows that layer-stacking DWs in 2D heterostructures provides opportunities to explore Luttinger liquid physics.

ADAMTS18 deficiency associates extracellular matrix dysfunction with a higher risk of HER2-positive mammary tumorigenesis and metastasis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for about 20% of all breast cancer cases and is correlated with a high relapse rate and poor prognosis. ADAMTS18 is proposed as an important functional tumor suppressor gene involved in multiple malignancies, including breast cancer. It functions as an extracellular matrix (ECM) modifier. However, it remains unclear whether ADAMTS18 affects mammary tumorigenesis and malignant progression through its essential ECM regulatory function. METHODS: To elucidate the role of ADAMTS18 in HER2-positive mammary tumorigenesis and metastasis in vivo, we compared the incidence of mammary tumor and metastasis between Adamts18-knockout (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18-/-) and Adamts18-wildtype (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18+/+). The underlying mechanisms by which ADAMTS18 regulates HER2-positive tumorigenesis and metastasis were investigated by pathology, cell culture, Western blot and immunochemistry. RESULTS: Adamts18 mRNA is mainly expressed in myoepithelial cells of the mammary duct. ADAMTS18 deficiency leads to a significantly increased incidence of mammary tumors and metastasis, as well as mammary hyperplasia in mice, over 30 months of observation. The proliferation, migration and invasion capacities of primary Her2t/w/Adamts18-/- mammary tumor cells are significantly higher than those of primary Her2t/w/Adamts18+/+ mammary tumor cells in vitro. At 30 months of age, the expression levels of laminin (LNα5), fibronectin (FN) and type I collagen (ColI) in the mammary glands of Her2t/w/Adamts18-/- mice are significantly increased, and the activities of integrin-mediated PI3K/AKT, ERK and JNK signaling pathways are enhanced. CONCLUSIONS: ADAMTS18 deficiency leads to alterations in mammary ECM components (e.g., LNα5, FN, ColI), which are associated with a higher risk of HER2-positive mammary tumorigenesis and metastasis.

Potato miR394 targets StA/N-INVE and StLCR to negatively regulate late blight resistance.

MicroRNAs (miRNAs) are small noncoding RNAs in eukaryotes. Plant endogenous miRNAs play pivotal roles in regulating plant development and defense responses. MicroRNA394 (miR394) has been reported to regulate plant development, abiotic stresses and defense responses. Previous reports showed that miR394 responded to P. infestans inoculation in potato, indicating that miR394 may be involved in defense responses. In this study, we further investigated its role in potato defense against P. infestans. Stable expression of miR394 in tobacco and potato enhances the susceptibility to P. infestans, which is accompanied with the reduced accumulation of ROS and down-regulation of the PTI (pattern-triggered immunity) marker genes. Besides well-known target StLCR, miR394 also targets StA/N-INVE, which encodes a chloroplast Alkaline/Neutral Invertases (A/N-INVE). Both StLCR and StA/N-INVE positively regulate late blight resistance, while miR394 degrades them. Interestingly, StA/N-INVE is located in the chloroplast, indicating that miR394 may manipulate chloroplast immunity. Degradation of StA/N-INVE may affect the chloroplast function and hence lead to the compromised ROS (reactive oxygen species) burst and reduced retrograde signaling from the chloroplast to the nucleus and cytoplasm. In summary, this study provides new information that miR394 targets and degrades StA/N-INVE and StLCR, which are positive regulators, to enhance potato susceptibility to P. infestans.

A Phytophthora effector promotes homodimerization of host transcription factor StKNOX3 to enhance susceptibility.

Oomycete pathogens secrete hundreds of cytoplasmic RxLR effectors to modulate host immunity by targeting diverse plant proteins. Revealing how effectors manipulate host proteins is pivotal to understanding infection processes and to developing new strategies to control plant disease. Here we show that the Phytophthora infestans RxLR effector Pi22798 interacts in the nucleus with a potato class II knotted-like homeobox (KNOX) transcription factor, StKNOX3. Silencing the ortholog NbKNOX3 in Nicotiana benthamiana reduces host colonization by P. infestans, whereas transient and stable overexpression of StKNOX3 enhances infection. StKNOX3 forms a homodimer which is dependent on its KNOX II domain. The KNOX II domain is also essential for Pi22798 interaction and for StKNOX3 to enhance P. infestans colonization, indicating that StKNOX3 homodimerization contributes to susceptibility. However, critically, the effector Pi22798 promotes StKNOX3 homodimerization, rather than heterodimerization to another KNOX transcription factor StKNOX7. These results demonstrate that the oomycete effector Pi22798 increases pathogenicity by promoting homodimerization specifically of StKNOX3 to enhance susceptibility.

Chloroplast protein StFC-II was manipulated by a Phytophthora effector to enhance host susceptibility.

Oomycete secretes a range of RxLR effectors into host cells to manipulate plant immunity by targeting proteins from several organelles. In this study, we report that chloroplast protein StFC-II is hijacked by a pathogen effector to enhance susceptibility. Phytophthora infestans RxLR effector Pi22922 is activated during the early stages of P. infestans colonization. Stable overexpression of Pi22922 in plants suppresses flg22-triggered reactive oxygen species (ROS) burst and enhances leaf colonization by P. infestans. A potato ferrochelatase 2 (FC-II, a nuclear-encoded chloroplast-targeted protein), a key enzyme for heme biosynthesis in chloroplast, was identified as a target of Pi22922 in the cytoplasm. The pathogenicity of Pi22922 in plants is partially dependent on FC-II. Overexpression of StFC-II decreases resistance of potato and Nicotiana benthamiana against P. infestans, and silencing of NbFC-II in N. benthamiana reduces P. infestans colonization. Overexpression of StFC-II increases heme content and reduces chlorophyll content and photosynthetic efficiency in potato leaves. Moreover, ROS accumulation both in chloroplast and cytoplasm is attenuated and defense-related genes are down-regulated in StFC-II overexpression transgenic potato and N. benthamiana leaves. Pi22922 inhibits E3 ubiquitin ligase StCHIP-mediated StFC-II degradation in the cytoplasm and promotes its accumulation in chloroplasts. In summary, this study characterizes a new mechanism that an oomycete RxLR effector suppresses host defenses by promoting StFC-II accumulation in chloroplasts, thereby compromising the host immunity and promoting susceptibility.

Diminished hedonic capacity in social activities as a mediator of the link between dysfunctional behavioral activation system and depressive symptoms.

Background: Adolescence is a crucial period for the development of depression, and previous studies have suggested that the Behavioral Activation System (BAS) plays a significant role. However, little is known about the underlying mechanisms. This study aimed to explore the mediating role of anhedonia in the relationship between BAS and depressive symptoms among Chinese adolescents. Method: A total of 1,023 high-school students aged 15-18 years participated in the study, with 916 continuing their participation three months later. All participants completed the Behavioral Inhibition System/Activation System (BIS/BAS) scale, Dimensional Anhedonia Rating Scale (DARS), Children's Depression Inventory (CDI), and the State-Trait Anxiety Inventory (STAI-S/T). Pathway model analysis was performed to examine the concurrent and prospective mediating effects of anhedonia and the potential moderating effect of sex. Result: Anhedonia in the domains of social activities, hobbies and sensory experiences significantly mediated the cross-sectional relationship between BAS and depressive level three months later. Furthermore, the beta-value of the mediating effect of social activities was significantly higher than that of the other domains of hedonic capacity cross-sectionally and longitudinally. However, sex showed no significant moderating effect. Conclusion: Our findings underscore the importance of hedonic capacity, especially within the social domain, in the development of depressive symptoms. These findings contribute to the early diagnosis and prevention of depressive disorders.

ADAMTS18-fibronectin interaction regulates the morphology of liver sinusoidal endothelial cells.

Liver sinusoidal endothelial cells (LSECs) have a unique morphological structure known as "fenestra" that plays a crucial role in liver substance exchange and homeostasis maintenance. In this study, we demonstrate that ADAMTS18 protease is primarily secreted by fetal liver endothelial cells. ADAMTS18 deficiency leads to enlarged fenestrae and increased porosity of LSECs, microthrombus formation in liver vessels, and an imbalance of liver oxidative stress. These defects worsen carbon tetrachloride (CCl4)-induced liver fibrosis and diethylnitrosamine (DEN)/high-fat-induced hepatocellular carcinoma (HCC) in adult Adamts18-deficient mice. Mechanically, ADAMTS18 functions as a modifier of fibronectin (FN) to regulate the morphological acquisition of LSECs via the vascular endothelial growth factor A (VEGFA) signaling pathways. Collectively, a mechanism is proposed for LSEC morphogenesis and liver homeostasis maintenance via ADAMTS18-FN-VEGFA niches.

Secreted protease ADAMTS18 in development and disease.

ADAMTS18 was identified in 2002 as a member of the ADAMTS family of 19 secreted Zinc-dependent metalloproteinases. Prior to 2016, ADAMTS18 was known as a candidate gene associated with a wide range of pathologies, particularly various malignancies and eye disorders. However, functions and substrates of ADAMTS18 in normal conditions were unknown. Since 2016, with the development of Adamts18 knockout models, many studies had been conducted on the Adamts18 gene in vivo. These studies revealed that ADAMTS18 is essential for the morphology and organogenesis of several epithelial organs (e.g., lung, kidney, breast, salivary glands, and lacrimal glands), vascular and neuronal systems, adipose tissue, and reproductive tracts. In this review, we describe the current understanding of ADAMTS18 and its substrates and regulators. Limitations in translating new findings on ADAMTS18 to clinical practice are also discussed.

Revealing the anti-melanoma mechanism of n-BuOH fraction from the red kidney bean coat extract based on network pharmacology and transcriptomic approach.

Red kidney bean coat (RKBC) extract contains bioactive compounds that are known to exhibit anti-melanoma activity in vitro. However, knowledge on antitumor component and mechanism of RKBC extract has not been fully clarified. Here, RKBC extract was portioned with different solvent sequentially, and based on the cell viability assay, cell migration assay, AO/EB and Hoechst 33342 staining assay, and Annexin V-FITC/PI double staining, n-BuOH (BU) fraction was identified as the most potent antitumor fraction. It exhibited potential anti-melanoma activity via the induction of apoptosis and vacuolization in B16-F10 cells. Transcriptomic and bioprocess-target network analysis revealed that BU fraction triggered apoptosis and vacuolization through regulating PI3K-AKT-FOXO, MDM2-p53 pathway and increasing the expression of Bcl-xl. In addition, quercetin might be served as one of the key anti-melanoma compounds in BU fraction through the similar mechanism. Although the anti-melanoma activity and mechanism of BU fraction have not been elucidated completely, this study effectively expands our understanding for the anti-melanoma activity of RKBC extract and provided the basis for the further functional food research and development using red kidney bean, as well as a new possibility for treating melanoma.

Polystyrene nanoplastics exposure caused defective neural tube morphogenesis through caveolae-mediated endocytosis and faulty apoptosis.

Growing evidence demonstrated that bioaccumulation of polystyrene nanoplastics (PS-NPs) in various organisms including human beings caused destructive effects on health. Nanoplastics may adversely affect fetal development potentially since they can pass through the placental barrier. However, very little has been known about the embryonic toxicity of polystyrene nanoplastics, especially in embryonic neurulation, the early developmental stage of the fetus, as well as the corresponding mechanisms. In this study, we first observed that 60- or 900-nm PS-NPs (especially 60-nm PS-NPs) could cross mouse placentas and affect developing mice fetuses. To avoid the indirect adverse effects derived from the restricted placenta, we employed early chick embryos as a developmental model to evaluate direct adverse effects of PS-NPs on embryo/fetal development, revealing suppressive effects on embryo development and an increased frequency of congenital abnormalities (especially in the nervous system), including neural tube defects. Thus, we focused on the potential negative effects of PS-NPs on neurulation, the earliest stage of nervous system development. Using caveolin-1 immunofluorescent staining of SH-SY5Y cells exposed to PS-NPs-GFP, we demonstrated that PS-NPs were internalized by SH-SY5Y cells via caveolae-mediated endocytosis. Transmission electron microscopy; LC3B immunofluorescent staining; and Atg7, Atg5, p62 and LC3B western blot results revealed that autophagy was activated in SH-SY5Y cells exposed to PS-NPs. However, PS-NPs were not degraded by the autophagic-lysosomal system given the lack of LAMP1 changes and minimal PS-NPs-GFP and LAMP1 colocalization. Furthermore, the cytoplasmic accumulation of PS-NPs caused faulty apoptotic cell death in SH-SY5Y cells and the developing neural tube as revealed by c-caspase3 immunofluorescent staining. Thus, defective neural tube morphogenesis, as demonstrated by neural tube defects, occurred during embryogenesis in the context of PS-NP exposure.

Three-Dimensional (3D) Nanostructured Skeleton Substrate Composed of Hollow Carbon Fiber/Carbon Nanosheet/ZnO for Stable Lithium Anode.

The practical applications of Li metal batteries (LMBs) have long been limited by the obstacles of low Coulombic efficiency (CE) and formation of dendrites on Li metal electrode. Herein, we demonstrated the synthesis of a novel three-dimensional (3D) nanostructured skeleton substrate composed of nitrogen-doped hollow carbon fiber/carbon nanosheets/ZnO (NHCF/CN/ZnO) using 2-methylimidazole (2-MIZ)-coated 3D cloth as a scaffold. The mechanism of formation of this novel hierarchical structure was investigated. The multilayered hierarchical structure and abundant lithiophilic nucleation sites of the substrate provide a stable environment for the deposition and stripping of lithium metal, thus preventing the generation of lithium dendrites. Consequently, the lithium anode based on the NHCF/CN/ZnO current collector demonstrated an excellent Coulombic efficiency of 96.47% after 400 cycles at 0.5 mA cm-2. The prepared NHCF/CN/ZnO/Li electrode also showed outstanding cycling performance of over 800 h and an ultralow voltage hysteresis of less than 30 mV in a symmetric cell at 5 mA cm-2 and 5 mAh cm-2. Even at a high loading of the cathode with 10.4 mg cm-2, the full cell of NHCF/CN/ZnO/Li anode with LiFePO4 can also work very well. Our work offers a path toward the facial preparation of 3D hierarchical structure for high-performance lithium metal batteries.

Comparison of two types of vinegar with different aging times by NMR-based metabolomic approach.

Shanxi vinegar (SV) is well known as the most famous vinegar for its distinctive processing technique in China. Aging is the most important process for SV, and we call the vinegar aging more than 1-year Shanxi aged vinegar (SAV) and less than 1-year Shanxi mature vinegar (SMV). In this study, the chemical compositions and in vivo difference between SAV and SMV were compared by NMR based metabolomic profiling technique and multivariate statistical analysis. The results indicated that most of the metabolites exhibited higher concentrations in SAV than those in SMV¸ and the amino acids showed higher concentration ratio than the other compounds. The changes of endogenous metabolites after treatment with SMV and SAV were also investigated. Compared with the chemical differences, the differences of metabolomic changes between SAV and SMV were relatively minor. This study provides a valuable approach for accurately evaluating the differences of food products. PRACTICAL APPLICATIONS: Vinegar is commonly consumed as the important seasoning. SV, which is made from several kinds of cereal by solid-state fermentation techniques, is one of the famous vinegars in China. Aging is the most important process for SV which dividing vinegar into SAV and SMV according to the aging time. Due to the long aging process, the price of SAV is much higher than that of SMV in the market place. However, no investigation was conducted to compare their differences in vivo.

Uncovering the anti-proliferation mechanism and bioactive compounds in red kidney bean coat against B16-F10 melanoma cells by metabolomics and network pharmacology analysis.

In this study, coat (RKBC) and kernel (RKBK) extracts of red kidney bean were prepared, and their chemical compositions and potential anti-cancer activity against B16-F10 cells were evaluated. Then the anti-proliferation mechanisms of the active RKBC extract were investigated by flow cytometry analysis, cellular metabolomics, network pharmacology and western blotting. The RKBC extract inhibited B16-F10 cell proliferation and migration in a dose-dependent manner. Further analysis showed that RKBC induced G1 and G2/M phase arrest, and triggered apoptosis and vacuolization. Mechanistically, RKBC significantly increased the cellular content of cGMP, decreased the levels of AKT1/2/3 and cleaved-MMP2, and up-regulated the expression of Bcl-xl. Besides, network pharmacology revealed that RKBC potentially influenced the cell cycle via the regulation of CDK2 and CDK4. Finally, quercetin might serve as the major active component in the RKBC extract. In conclusion, our study showed the potential of the RKBC extract for the prevention or treatment of melanoma.

Sulforaphane Rescues Ethanol-Suppressed Angiogenesis through Oxidative and Endoplasmic Reticulum Stress in Chick Embryos.

Our previous study showed that ethanol exposure inhibited embryonic angiogenesis mainly due to the excessive stimulation of reactive oxygen species (ROS) production. In this study, we investigated whether sulforaphane (SFN), a known dietary bioactive compound, could ameliorate ethanol-suppressed angiogenesis using chick embryo angiogenesis models. Using chick yolk sac membrane (YSM) and chorioallantoic membrane (CAM) models, we demonstrated that administration of low concentrations of SFN (2.5-10 µM) alone increased angiogenesis, but high concentrations of SFN (20-40 µM) inhibited angiogenesis. SFN administration alleviated ethanol-suppressed angiogenesis and angiogenesis-related gene expression in both angiogenesis models. Ethanol exposure caused cell apoptosis in chick CAM, and the cell apoptosis could be remitted by administration of SFN. Subsequently, we demonstrated that the ethanol-induced increase in production of ROS and reduction of antioxidant enzymes' activity were partially rescued by SFN. Similar results were obtained in endoplasmic reticulum (ER) stress determination, indicated by ATF6 and GRP78 expression or thapsigargin-induced ER stress in the presence or absence of SFN. Taken together, our experiments show that SFN administration can ameliorate ethanol-suppressed embryonic angiogenesis, and this is mainly achieved by alleviating excessive ROS production and ER stress. This study suggests that SFN, in appropriate concentrations, could be a potential candidate compound for preventing the negative impact of alcohol on angiogenesis.