Dyakonov-Perel-like Orbital and Spin Relaxations in Centrosymmetric Systems.

The Dyakonov-Perel (DP) mechanism of spin relaxation has long been considered irrelevant in centrosymmetric systems since it was developed originally for noncentrosymmetric ones. We investigate whether this conventional understanding extends to the realm of orbital relaxation, which has recently attracted significant attention. Surprisingly, we find that orbital relaxation in centrosymmetric systems exhibits the DP-like behavior in the weak scattering regime. Moreover, the DP-like orbital relaxation can make the spin relaxation in centrosymmetric systems DP-like through the spin-orbit coupling. We also find that the DP-like orbital and spin relaxations are anisotropic even in materials with high crystal symmetry (such as face-centered cubic structure) and may depend on the orbital and spin nature of electron wave functions.

Graphislactone A, a Fungal Antioxidant Metabolite, Reduces Lipogenesis and Protects against Diet-Induced Hepatic Steatosis in Mice.

Graphislactone A (GPA), a secondary metabolite derived from a mycobiont found in the lichens of the genus Graphis, exhibits antioxidant properties. However, the potential biological functions and therapeutic applications of GPA at the cellular and animal levels have not yet been investigated. In the present study, we explored the therapeutic potential of GPA in mitigating non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms through a series of experiments using various cell lines and animal models. GPA demonstrated antioxidant capacity on a par with that of vitamin C in cultured hepatocytes and reduced the inflammatory response induced by lipopolysaccharide in primary macrophages. However, in animal studies using an NAFLD mouse model, GPA had a milder impact on liver inflammation while markedly attenuating hepatic steatosis. This effect was confirmed in an animal model of early fatty liver disease without inflammation. Mechanistically, GPA inhibited lipogenesis rather than fat oxidation in cultured hepatocytes. Similarly, RNA sequencing data revealed intriguing associations between GPA and the adipogenic pathways during adipocyte differentiation. GPA effectively reduced lipid accumulation and suppressed lipogenic gene expression in AML12 hepatocytes and 3T3-L1 adipocytes. In summary, our study demonstrates the potential application of GPA to protect against hepatic steatosis in vivo and suggests a novel role for GPA as an underlying mechanism in lipogenesis, paving the way for future exploration of its therapeutic potential.

A network analysis of suicidal ideation, depressive symptoms, and subjective well-being in a community population.

Although the relationship between subjective well-being (SWB) and suicidal ideation (SI) has been illustrated in previous research, few studies have conceptualized SWB as a comprehensive measure of life satisfaction in multiple domains, nor have they considered possible mediators such as depressive symptoms. Therefore, the present study aimed to identify dimensions of SWB correlated with SI, and to analyze associations among SWB sub-domains, depressive symptoms, and SI in a community population. A total of 1200 community adults in South Korea, aged 20-86 years, completed self-report questionnaires on demographics, depressive mood (Patient Health Questionnaire-9 [PHQ-9]), SI (item 9 of the PHQ-9), and 14 SWB sub-domains (Subjective Well-Being Inventory). Factors associated with SI, and interactions among SI, depressive mood, and SWB, were identified by logistic regression and phenotype network analyses, respectively. The five main factors influencing the regularized partial correlation network were life satisfaction, self-blame, job, hopelessness, and fatigue. Pathways were observed from work-life balance and life satisfaction to hopelessness; from self-blame and fatigue to safety and health; and from sleep disturbance, concentration difficulties, self-blame, and hopelessness to SI. Making job activities more emotionally rewarding, the potential for career progression and regular work hours could address anhedonia, hopelessness and sleep disturbance, respectively, thus enhancing SWB and reducing SI in the community population.

Non-Fermi Liquids in Conducting Two-Dimensional Networks.

We explore the physics of novel fermion liquids emerging from conducting networks, where 1D metallic wires form a periodic 2D superstructure. Such structure naturally appears in marginally twisted bilayer graphenes, moire transition metal dichalcogenides, and also in some charge-density wave materials. For these network systems, we theoretically show that a remarkably wide variety of new non-Fermi liquids emerge and that these non-Fermi liquids can be classified by the characteristics of the junctions in networks. Using this, we calculate the electric conductivity of the non-Fermi liquids as a function of temperature, which show markedly different scaling behaviors than a regular 2D Fermi liquid.

Stable Flatbands, Topology, and Superconductivity of Magic Honeycomb Networks.

We propose a new principle to realize flatbands which are robust in real materials, based on a network superstructure of one-dimensional segments. This mechanism is naturally realized in the nearly commensurate charge-density wave of 1T-TaS_{2} with the honeycomb network of conducting domain walls, and the resulting flatband can naturally explain the enhanced superconductivity. We also show that corner states, which are a hallmark of the higher-order topological insulators, appear in the network superstructure.

CDA: combinatorial drug discovery using transcriptional response modules.

BACKGROUND: Anticancer therapies that target single signal transduction pathways often fail to prevent proliferation of cancer cells because of overlapping functions and cross-talk between different signaling pathways. Recent research has identified that balanced multi-component therapies might be more efficacious than highly specific single component therapies in certain cases. Ideally, synergistic combinations can provide 1) increased efficacy of the therapeutic effect 2) reduced toxicity as a result of decreased dosage providing equivalent or increased efficacy 3) the avoidance or delayed onset of drug resistance. Therefore, the interest in combinatorial drug discovery based on systems-oriented approaches has been increasing steadily in recent years. METHODOLOGY: Here we describe the development of Combinatorial Drug Assembler (CDA), a genomics and bioinformatics system, whereby using gene expression profiling, multiple signaling pathways are targeted for combinatorial drug discovery. CDA performs expression pattern matching of signaling pathway components to compare genes expressed in an input cell line (or patient sample data), with expression patterns in cell lines treated with different small molecules. Then it detects best pattern matching combinatorial drug pairs across the input gene set-related signaling pathways to detect where gene expression patterns overlap and those predicted drug pairs could likely be applied as combination therapy. We carried out in vitro validations on non-small cell lung cancer cells and triple-negative breast cancer (TNBC) cells. We found two combinatorial drug pairs that showed synergistic effect on lung cancer cells. Furthermore, we also observed that halofantrine and vinblastine were synergistic on TNBC cells. CONCLUSIONS: CDA provides a new way for rational drug combination. Together with phExplorer, CDA also provides functional insights into combinatorial drugs. CDA is freely available at http://cda.i-pharm.org.

Rational drug repositioning guided by an integrated pharmacological network of protein, disease and drug.

BACKGROUND: The process of drug discovery and development is time-consuming and costly, and the probability of success is low. Therefore, there is rising interest in repositioning existing drugs for new medical indications. When successful, this process reduces the risk of failure and costs associated with de novo drug development. However, in many cases, new indications of existing drugs have been found serendipitously. Thus there is a clear need for establishment of rational methods for drug repositioning. RESULTS: In this study, we have established a database we call "PharmDB" which integrates data associated with disease indications, drug development, and associated proteins, and known interactions extracted from various established databases. To explore linkages of known drugs to diseases of interest from within PharmDB, we designed the Shared Neighborhood Scoring (SNS) algorithm. And to facilitate exploration of tripartite (Drug-Protein-Disease) network, we developed a graphical data visualization software program called phExplorer, which allows us to browse PharmDB data in an interactive and dynamic manner. We validated this knowledge-based tool kit, by identifying a potential application of a hypertension drug, benzthiazide (TBZT), to induce lung cancer cell death. CONCLUSIONS: By combining PharmDB, an integrated tripartite database, with Shared Neighborhood Scoring (SNS) algorithm, we developed a knowledge platform to rationally identify new indications for known FDA approved drugs, which can be customized to specific projects using manual curation. The data in PharmDB is open access and can be easily explored with phExplorer and accessed via BioMart web service (http://www.i-pharm.org/, http://biomart.i-pharm.org/).

QTL mapping and molecular marker analysis for the resistance of rice to ozone.

The resistance of rice to ozone (O3) is a quantitative trait controlled by nuclear genes. The identification of quantitative trait loci (QTL) and analysis of molecular markers of O3 resistance is important for increasing the resistance of rice to O3 stress. QTL associated with the O3 resistance of rice were mapped on chromosomes 1, 7 and 11 using 164 recombinant inbred (RI) lines from a cross between 'Milyang 23' and 'Gihobyeo'. The quantitative trait loci were tightly linked to the markers RG109, C507 and RG1094 and were detected in each of three replications. The association between these markers and O3 resistance in 26 rice cultivars and doubled haploid (DH) populations was analysed. The markers permit the screening of rice germplasm for O3 resistance and the introduction of resistance into elite lines in breeding programs.