To decipher the underlying mechanisms of Sanleng-Ezhu for the treatment of idiopathic pulmonary fibrosis based on network pharmacology and single-cell RNA sequencing data. Idiopathic Pulmonary Fibrosis (IPF) is the most common type of interstitial lung disease. Although the combination of herbs Sanleng (SL) and Ezhu (EZ) has shown reliable efficacy in the management of IPF, its underlying mechanisms remain unknown. Based on LC-MS/MS analysis and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, we identified the bioactive components of SL-EZ. After obtaining the IPF-related dataset GSE53845 from the Gene Expression Omnibus (GEO) database, we performed the differential expression analysis and the weighted gene co-expression network analysis (WGCNA), respectively. We obtained lowly and highly expressed IPF subtype gene sets by comparing Differentially Expressed Genes (DEGs) with the most significantly negatively and positively related IPF modules in WGCNA. Subsequently, we performed Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on IPF subtype gene sets. The low- and highexpression MCODE subgroup feature genes were identified by the MCODE plug-in and were adopted for Disease Ontology (DO), GO, and KEGG enrichment analyses. Next, we performed the immune cell infiltration analysis of the MCODE subgroup feature genes. Single-cell RNA sequencing analysis demonstrated the cell types which expressed different MCODE subgroup feature genes. Molecular docking and animal experiments validated the effectiveness of SL-EZ in delaying the progression of pulmonary fibrosis. We obtained 5 bioactive components of SL-EZ as well as their corresponding 66 candidate targets. After normalizing the samples of the GSE53845 dataset from the GEO database source, we obtained 1907 DEGs of IPF. Next, we performed a WGCNA analysis on the dataset and got 11 modules. Notably, we obtained 2 IPF subgroups by contrasting the most significantly up- and down-regulated modular genes in IPF with DEGs, respectively. The different IPF subgroups were compared with drugcandidate targets to obtain direct targets of action. After constructing the protein interaction networks between IPF subgroup genes and drug candidate targets, we applied the MCODE plug-in to filter the highest-scoring MCODE components. DO, GO, and KEGG enrichment analyses were applied to drug targets, IPF subgroup genes, and MCODE component signature genes. In addition, we downloaded the single-cell dataset GSE157376 from the GEO database. By performing quality control and dimensionality reduction, we clustered the scattered primary sample cells into 11 clusters and annotated them into 2 cell subtypes. Drug sensitivity analysis suggested that SL-EZ acts on different cell subtypes in IPF subgroups. Molecular docking revealed the mode of interaction between targets and their corresponding components. Animal experiments confirmed the efficacy of SL-EZ. We found SL-EZ acted on epithelial cells mainly through the calcium signaling pathway in the lowly-expressed IPF subtype, while in the highly-expressed IPF subtype, SL-EZ acted on smooth muscle cells mainly through the viral infection, apoptosis, and p53 signaling pathway.

Generally, the dissipationless Hall effect in solids requires time-reversal symmetry breaking (TRSB), where TRSB induced by external magnetic field results in the ordinary Hall effect, while TRSB caused by spontaneous magnetization gives rise to the anomalous Hall effect (AHE) which scales with the net magnetization. The AHE is therefore not expected in antiferromagnets with vanishing small magnetization. However, large AHE was recently observed in certain antiferromagnets with noncollinear spin structure and nonvanishing Berry curvature. Here, we report another origin of AHE in a layered antiferromagnet EuAl_{2}Si_{2}, namely, the domain wall (DW) skew scattering with Weyl points near the Fermi level, in experiments for the first time. Interestingly, the DWs form a unique periodic stripe structure with controllable periodicity by external magnetic field, which decreases nearly monotonically from 975nm at 0T to 232nm at 4T. Electrons incident on DW with topological bound states experience strong asymmetric scattering, leading to a giant AHE, with the DW Hall conductivity (DWHC) at 2K and 1.2T reaching a record value of ∼1.51×10^{4} Scm^{-1} among bulk systems and being 2 orders of magnitude larger than the intrinsic anomalous Hall conductivity. The observation not only sets a new paradigm for exploration of large anomalous Hall effect, but also provides potential applications in spintronic devices.

We analyze a class of Cahn–Hilliard equations with kinetic rate dependent dynamic boundary conditions that describe possible short-range interactions between the binary mixture and the solid boundary. In the presence of surface diffusion on the boundary, the initial boundary value problem can be viewed as a transmission problem consisting of Cahn–Hilliard-type equations both in the bulk and on the boundary. We first establish the existence, uniqueness, and continuous dependence of global weak solutions. In the construction of weak solutions, an explicit convergence rate in terms of the parameter for the Yosida approximation is obtained. Under some additional assumptions, we further prove the existence and uniqueness of global strong solutions. Next, we study the asymptotic limit as the coefficient of the boundary diffusion goes to zero and show that the limit problem with a forward-backward dynamic boundary condition is well posed in a suitable weak formulation. At last, we investigate the asymptotic limits as the kinetic rate tends to zero and infinity, respectively. Our results are valid for a general class of bulk and boundary potentials with double-well structure, including the physically relevant logarithmic potential and the non-smooth double obstacle potential.