TEAD2 initiates ground-state pluripotency by mediating chromatin looping.

The transition of mouse embryonic stem cells (ESCs) between serum/LIF and 2i(MEK and GSK3 kinase inhibitor)/LIF culture conditions serves as a valuable model for exploring the mechanisms underlying ground and confused pluripotent states. Regulatory networks comprising core and ancillary pluripotency factors drive the gene expression programs defining stable naïve pluripotency. In our study, we systematically screened factors essential for ESC pluripotency, identifying TEAD2 as an ancillary factor maintaining ground-state pluripotency in 2i/LIF ESCs and facilitating the transition from serum/LIF to 2i/LIF ESCs. TEAD2 exhibits increased binding to chromatin in 2i/LIF ESCs, targeting active chromatin regions to regulate the expression of 2i-specific genes. In addition, TEAD2 facilitates the expression of 2i-specific genes by mediating enhancer-promoter interactions during the serum/LIF to 2i/LIF transition. Notably, deletion of Tead2 results in reduction of a specific set of enhancer-promoter interactions without significantly affecting binding of chromatin architecture proteins, CCCTC-binding factor (CTCF), and Yin Yang 1 (YY1). In summary, our findings highlight a novel prominent role of TEAD2 in orchestrating higher-order chromatin structures of 2i-specific genes to sustain ground-state pluripotency.

Single-cell transcriptomics reveals peripheral immune responses in non-segmental vitiligo.

Background: Vitiligo is a common autoimmune depigmented dermatology due to destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, but few studies have investigated the cell types and function of circulating immune cells in peripheral blood. Here, single cell RNA-sequencing (scRNA-seq) was used to investigate the mechanisms of peripheral immune responses in vitiligo patients. Methods: Peripheral blood was collected from five patients with progressive non-segmental vitiligo and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Paque density gradient centrifugation, and scRNA-seq was performed on isolated cell populations to obtain single cell transcriptomes and characterize important genes and intracellular signaling pathways. The key findings were validated with qPCR and flow cytometry assays. Results: We identified 10 major cell types by scRNA-seq. Among these cell types, neutrophils were specifically observed in our scRNA-seq data from PBMCs. Peripheral blood effector CD8+ T cells from vitiligo patients did not show significant differences at the transcriptome level compared with healthy controls, whereas regulatory T cells showed pro-inflammatory TH1-like properties. Innate immune cells, including natural killer cells and dendritic cells, showed increased antigen processing and presentation as well as upregulated interferon responses. B cells, monocytes, and neutrophils all showed activation. B cells, especially memory B cells, had upregulated expression of genes related to humoral immunity. Monocytes showed production of proinflammatory cytokines and chemokines. Neutrophils showed strong chemokine ligand-receptor (L-R) pair (CXCR8-CXCR2) autocrine signaling pathway. Conclusion: This study revealed the genetic profile and signaling pathway characteristics of peripheral blood immune cells in vitiligo patients, providing new insights into its pathogenesis, which may facilitate identification of potential therapeutic targets.

Metagenomic sequencing reveals altered gut microbial compositions and gene functions in patients with non-segmental vitiligo.

BACKGROUND: Vitiligo has been correlated with an abnormal gut microbiota. We aimed to systematically identify characteristics of the gut microbial compositions, genetic functions, and potential metabolic features in patients with non-segmental vitiligo. METHODS: Twenty-five patients with non-segmental vitiligo and 25 matched healthy controls (HCs) were enrolled. Metagenomic sequencing and bioinformatic analysis were performed to determine the gut microbiota profiles. Differences in gut microbiota diversity and composition between patients with vitiligo and HCs were analyzed. Gene functions and gut metabolic modules were predicted with the Kyoto Encyclopedia of Gene and Genomes (KEGG) and MetaCyc databases. RESULTS: Compared with HCs, alpha diversity of intestinal microbiome in vitiligo patients was significantly reduced. At the species level, the relative abundance of Staphylococcus thermophiles was decreased, and that of Bacteroides fragilis was increased in patients with vitiligo compared with those of the HCs. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed representative microbial markers of Lachnospiraceae_bacterium_BX3, Massilioclostridium_coli, TM7_phylum_sp_oral_taxon_348 and Bacteroides_fragilis for patients with vitiligo. KEGG gene function analysis showed that the NOD-like receptor signaling pathway was significantly enriched in patients with vitiligo. Gut metabolic modules (GMMs) analysis showed that cysteine degradation was significantly down-regulated, and galactose degradation was up-regulated in patients with vitiligo. A panel of 28 microbial features was constructed to distinguish patients with vitiligo from HCs. CONCLUSIONS: The gut microbial profiles and genetic functions of patients with vitiligo were distinct from those of the HCs. The identified gut microbial markers may potentially be used for earlier diagnosis and treatment targets.

Single-atom boosted electrochemiluminescence via phosphorus doping of Fe-N/P-C catalysts.

Single-atom catalyst (SAC), one of the most attractive catalysts in the field of energy conversion and storage, was proven as efficient accelerator for luminol-dissolved oxygen electrochemiluminescence (ECL) via the catalysis of oxygen reduction reaction (ORR). In this work, we synthesized heteroatom doping SACs of Fe-N/P-C for the catalysis of cathodic luminol ECL. The doping of P could lower the reaction energy barrier of the OH* reduction, and promote catalytic efficiency toward ORR. The formation of reactive oxygen species (ROS) during ORR triggered cathodic luminol ECL. Greatly enhanced ECL emission catalyzed by SACs proved that Fe-N/P-C exhibited higher catalytic activity to ORR compared with Fe-N-C. Since the system was highly dependent on oxygen, an ultra-sensitive detection of a typical antioxidant, ascorbic acid, was achieved with detection limit of 0.03 nM. This study provides possibility to greatly enhance the performance of ECL platform through rational tailoring of SACs via heteroatom doping.

Isomeric Effect of Wide Bandgap Polymer Donors with High Crystallinity to Achieve Efficient Polymer Solar Cells.

Two highly crystalline polymer donors (PBTz4T2C-a, PBTz4T2C-b) with isomers (4T2C-a, 4T2C-b) are synthesized and applied in polymer solar cells. The developed polymers possess proper energy levels and complementary absorption with an efficient electron acceptor IT2F. It is interesting that the photophysical properties, crystallinity, and active layer morphology characteristic can be significantly changed by just slightly regulating the substitution position of the carboxylate groups. A series of simulation calculations of the two isomers are conducted in the geometry and electronic properties to explore the difference induced by the position adjustment of carboxylate groups. The results decipher that 4T2C-b moiety features much stronger intramolecular noncovalent S⋯O interactions compared to that of 4T2C-a, implying a higher coplanarity and much stronger crystallinity, and leading to excessive phase separation in PBTz4T2C-b:IT2F blend film. In contrast, PBTz4T2C-a with 4T2C-a moiety exhibits suitable crystallinity with a lower the highest occupied molecular orbital level, higher film absorption coefficient, and charge mobilities, resulting in a much higher power conversion efficiency of 11.02%. This research demonstrates that the molecular conformation is of great importance to be considered for developing high-performance polymer donors.

Introducing Porphyrin Units by Random Copolymerization Into NDI-Based Acceptor for All Polymer Solar Cells.

Naphthalene diimide (NDI)-based polymer N2200 is a promising organic polymer acceptor for all-polymer solar cells (all-PSCs), but its inherent shortcomings like poor extinction coefficient and strong aggregation limit further performance optimization of all-PSCs. Here, a series of random copolymers, PNDI-Px, were designed and synthesized by introducing porphyrin unit into NDI-based polymer as acceptors for all-PSCs. These random copolymers show a higher absorption coefficient and raised the lowest unoccupied molecular orbital (LUMO) energy levels compared to N2200. The crystallinity can also be fine-tuned by regulation of the content of porphyrin unit. The random copolymers are matched with polymer donor PBDB-T for the application in all-polymer solar cells. The best power conversion efficiency (PCE) of these PNDI-Px-based devices is 5.93%, ascribed to the overall enhanced device parameters compared with the N2200-based device. These results indicate that introducing porphyrin unit into polymer is a useful way to fine-tune the photoelectric performance for efficient all-PSCs.

Unraveling the Morphology in Solution-Processed Pseudo-Bilayer Planar Heterojunction Organic Solar Cells.

The conventional bulk heterojunction (BHJ) structure is widely used for fabricating high-performance organic solar cells (OSCs) due to the nanometer-scale phase separation of the donor/acceptor component. However, the elaborate control of the BHJ morphology is difficult to carry out because the morphology evolution is such a complicated process. The compatibility requirement of materials in the same solvent restricts the structural diversity of the molecules to some extent. Meanwhile, the nanoscopic interpenetrating donor/acceptor domains reduce their crystallinity. The bilayer planar heterojunction (PHJ), by contrast, possesses complementary advantages that can make it an alternative candidate to achieve device fabrication and produce different vertical stratification in heterojunction films. However, the flat contact area limits the charge separation and transmission efficiency. The sequential solution processed approach was used to facilitate material diffusion in layers. Also, solvent additives were employed to further enhance the diffusion and thus the device performance. Nevertheless, the morphology of the formed pseudo-bilayer planar heterojunction (PPHJ) has not been fully revealed yet. Here, we carefully study the morphology of the nonfullerene-based PPHJ device in three dimensions. High hole mobility of 2.09 × 10-4 cm2 V-1 s-1 and electron mobility of 7.91 × 10-5 cm2 V-1 s-1 were obtained in the solution-processed PPHJ device. Meanwhile, a distinct phase separation size with a vertical rearrangement of donor and acceptor was observed, which enable the pseudo-bilayer devices to be equipped with a comparable spectral response to the BHJ devices. We demonstrate that a unique device architecture (ITO/ZnO/PBDB-T/ITIC/MoO3/Ag) with a power conversion efficiency of 7% can be obtained from a larger molecular weight of PBDB-T without using extra additives. The solution-processed PPHJ films have much in common with the BHJ films. The results proposed that with appropriate molecular design and vertical phase separation optimization, the performance of the solution-processed PPHJ-based OSCs can be further improved.