Aging in the dermis: Fibroblast senescence and its significance

Skin aging is characterized by changes in its structural, cellular, and molecular components in both the epidermis and dermis. Dermal aging is distinguished by reduced dermal thickness, increased wrinkles, and a sagging appearance. Due to intrinsic or extrinsic factors, accumulation of excessive reactive oxygen species (ROS) triggers a series of aging events, including imbalanced extracellular matrix (ECM) homeostasis, accumulation of senescent fibroblasts, loss of cell identity, and chronic inflammation mediated by senescence-associated secretory phenotype (SASP). These events are regulated by signaling pathways, such as nuclear factor erythroid 2-related factor 2 (Nrf2), mechanistic target of rapamycin (mTOR), transforming growth factor beta (TGF-β), and insulin-like growth factor 1 (IGF-1). Senescent fibroblasts can induce and accelerate age-related dysfunction of other skin cells and may even cause systemic inflammation. In this review, we summarize the role of dermal fibroblasts in cutaneous aging and inflammation. Moreover, the underlying mechanisms by which dermal fibroblasts influence cutaneous aging and inflammation are also discussed.     

Three new red neutral and ionic iridium(III) complexes based on the same main ligand and auxiliary ligand but with different counterions for solution-processed organic light-emitting diodes

Three new neutral and ionic phosphorescent iridium(III) complexes were successfully prepared using 1-(6-methoxynaphthalen-2-yl)isoquinoline as the main ligand, while the auxiliary ligand was 2-(2-1H-imidazolyl)pyridine. Three complexes (Ir1, Ir2, Ir3) showed red emission, peaking at 610, 609, and 615 nm, respectively, and they exhibited good solubility and excellent photophysical properties in different solvents, which is suitable to prepare organic light-emitting diodes (OLEDs) by solution method. Among the three OLEDs prepared by iridium(III) complexes using the solution method, the device based on Ir2 possessed better electroluminescent properties, and its maximum brightness, current efficiency (CE), power efficiency (PE), and the maximum external quantum efficiency (EQE) were 507.2 cd m⁻², 0.14 cd A⁻¹, 0.06 lm W⁻¹, and 0.14%. respectively, proving that the three complexes have a certain of potential for OLEDs applications and are expected to expand the applications of iridium(III) complexes for OLEDs.     

Efficiency Boost in All-Small-Molecule Organic Solar Cells: Insights from the Re-Ordering Kinetics

Achieving high-performance in all-small-molecule organic solar cells (ASM-OSCs) significantly relies on precise nanoscale phase separation through domain size manipulation in the active layer. Nonetheless, for ASM-OSC systems, forging a clear connection between the tuning of domain size and the intricacies of phase separation proves to be a formidable challenge. This study investigates the intricate interplay between domain size adjustment and the creation of optimal phase separation morphology, crucial for ASM-OSCs’ performance. It is demonstrated that exceptional phase separation in ASM-OSCs’ active layer is achieved by meticulously controlling the continuity and uniformity of domains via re-packing process. A series of halogen-substituted solvents (Fluorobenzene, Chlorobenzene, Bromobenzene, and Iodobenzene) is adopted to tune the re-packing kinetics, the ASM-OSCs treated with CB exhibited an impressive 16.2% power conversion efficiency (PCE). The PCE enhancement can be attributed to the gradual crystallization process, promoting a smoothly interconnected and uniformly distributed domain size. This, in turn, leads to a favorable phase separation morphology, enhanced charge transfer, extended carrier lifetime, and consequently, reduced recombination of free charges. The findings emphasize the pivotal role of re-packing kinetics in achieving optimal phase separation in ASM-OSCs, offering valuable insights for designing high-performance ASM-OSCs fabrication strategies.     

Solvent-Mediated Synthesis of Functional Powder Materials from Deep Eutectic Solvents for Energy Storage and Conversion: A Review

Developing advanced electrochemical energy storage and conversion (ESC) technologies based on renewable clean energy can alleviate severe global environmental pollution and energy crisis. The efficient preparation of functional electrode materials via a simple, green, and safe synthesis process is the key to the commercial feasibility of these ESC systems. Deep eutectic solvents (DESs) with easy-tunable solvent properties and recyclable features have emerged as novel solvent systems for designing and synthesizing various functional powder materials for ESC devices. In this paper, the application of DESs in the synthesis of energy-related functional powder materials is systematically reviewed. After briefly introducing the classification and synthesis of DESs, their critical roles in synthesizing powder materials are discussed. Then, the recent advances of DES-derived powder materials in ESC, including batteries, fuel cells, supercapacitors, and water splitting, are described in detail from the perspective of preparation-structure-activity. Finally, some challenges and development directions of the DESs-mediated synthesis of powder materials with high electrochemical performance for ESC applications are outlined.     

Inhibiting Dendrite Formation and Electrode Corrosion via a Scalable Self-Assembled Mercaptan Layer for Stable Aqueous Zinc Batteries

The practical use of Zn metal anodes in aqueous zinc batteries is impeded by the growth of dendrites, anode corrosion, and hydrogen evolution reaction in aqueous electrolytes. In this study, a simple, energy-efficient, and scalable approach is reported to mitigate these detrimental issues effectively. Using 1-hexanethiol (HT), a hydrophobic self-assembled mercaptan layer (SAML) with a highly ordered structure is in situ created on the surface of the Zn anode. This ultrathin interfacial structure guides uniform Zn deposition and shields the Zn anode from water and oxygen-induced corrosion, thus effectively inhibiting dendrite formation and side reactions. Consequently, the HT-Zn electrode showcases impressive electrochemical stability and reversibility, and the as-assembled HT-Zn||I₂ full cell delivers increased specific capacity (from 112 to 155 mAh g⁻¹ at 1 A g⁻¹) and ultra-stable cyclability (zero capacity decay during the extended 1500 cycles at 4 A g⁻¹). To validate the effectiveness of this simple and scalable method, a large-sized pouch cell is prepared, which can be stably operated for 1000 cycles with a capacity decay of merely 0.0098% per cycle and Coulombic efficiency exceeding 99.1%. The presented SAML strategy highlights the potential of molecular engineering in improving the performance of aqueous zinc batteries.     

Single-Atom Immobilization Boosting Oxygen Redox Kinetics of High-Entropy Perovskite Oxide Toward High-Performance Lithium-Oxygen Batteries

Understanding and modulating the unique electronic interaction between single-metal atoms and high entropy compounds are of great significance to enable their high-efficiency oxygen electrocatalysis for aprotic lithium-oxygen (Li-O₂) batteries. Herein, a novel bi-functional electrocatalyst is for the first time created by immobilizing single-atom ruthenium (Ru) on lanthanum-based high entropy perovskite oxide La(Mn_0.2Co_0.2Fe_0.2Ni_0.2Cr_0.2)O₃ (Ru@HEPO), which demonstrates high activity and stability in Li-O₂ batteries. The heteronuclear coordination between single-atom Ru and HEPO facilitates fast electron transfer from Ru to HEPO by establishing Ru-O-M (M stands for Mn, Co, Fe, Ni) bridges, which well redistributes electrons within the Ru@HEPO hence significantly improving its interfacial charge transfer kinetics and electrocatalytic activity. Additionally, the strong electron coupling between Ru and Mn atoms enhances the hybridization between Mn 3d and O 2p orbitals, which promotes the inherent affinity of Ru@HEPO toward the LiO₂ intermediate, thereby reducing the reaction energy barrier of the oxygen electrode. As a result, the Ru@HEPO-based Li-O₂ batteries deliver remarkable electrochemical performances, such as high energy efficiency (87.3% at 100 mA g⁻¹), excellent rate capability (low overpotential of 0.52 V at 100 mA g⁻¹) and durable cyclability (345 cycles at 300 mA g⁻¹). This work opens up a promising avenue for the development of high entropy-based electrocatalysts for Li-O₂ batteries by precisely tailoring the electronic distributions at an atomic scale.     

Anti‐hsa‐miR‐59 alleviates premature senescence associated with Hutchinson‐Gilford progeria syndrome in mice

Hutchinson‐Gilford progeria syndrome (HGPS) is a lethal premature aging disorder without an effective therapeutic regimen. Because of their targetability and influence on gene expression, microRNAs (miRNAs) are attractive therapeutic tools to treat diseases. Here we identified that hsa‐miR‐59 (miR‐59) was markedly upregulated in HGPS patient cells and in multiple tissues of an HGPS mouse model (Lmna ^G609G/G609G ), which disturbed the interaction between RNAPII and TFIIH, resulting in abnormal expression of cell cycle genes by targeting high‐mobility group A family HMGA1 and HMGA2. Functional inhibition of miR‐59 alleviated the cellular senescence phenotype of HGPS cells. Treatment with AAV9‐mediated anti‐miR‐59 reduced fibrosis in the quadriceps muscle, heart, and aorta, suppressed epidermal thinning and dermal fat loss, and yielded a 25.5% increase in longevity of Lmna ^G609G/G609G mice. These results identify a new strategy for the treatment of HGPS and provide insight into the etiology of HGPS disease.     

Role of PCIF1‐mediated 5′‐cap N6‐methyladeonsine mRNA methylation in colorectal cancer and anti‐PD‐1 immunotherapy

Adenosine N6‐methylation (m6A) and N6,2′‐O‐dimethylation (m6Am) are regulatory modifications of eukaryotic mRNAs. m6Am formation is catalyzed by the methyl transferase phosphorylated CTD‐interacting factor 1 (PCIF1); however, the pathophysiological functions of this RNA modification and PCIF1 in cancers are unclear. Here, we show that PCIF1 expression is upregulated in colorectal cancer (CRC) and negatively correlates with patient survival. CRISPR/Cas9‐mediated depletion of PCIF1 in human CRC cells leads to loss of cell migration, invasion, and colony formation in vitro and loss of tumor growth in athymic mice. Pcif1 knockout in murine CRC cells inhibits tumor growth in immunocompetent mice and enhances the effects of anti‐PD‐1 antibody treatment by decreasing intratumoral TGF‐β levels and increasing intratumoral IFN‐γ, TNF‐α levels, and tumor‐infiltrating natural killer cells. We further show that PCIF1 modulates CRC growth and response to anti‐PD‐1 in a context‐dependent mechanism with PCIF1 directly targeting FOS, IFITM3, and STAT1 via m6Am modifications. PCIF1 stabilizes FOS mRNA, which in turn leads to FOS‐dependent TGF‐β regulation and tumor growth. While during immunotherapy, Pcif1‐Fos‐TGF‐β, as well as Pcif1‐Stat1/Ifitm3‐IFN‐γ axes, contributes to the resistance of anti‐PD‐1 therapy. Collectively, our findings reveal a role of PCIF1 in promoting CRC tumorigenesis and resistance to anti‐PD‐1 therapy, supporting that the combination of PCIF1 inhibition with anti‐PD‐1 treatment is a potential therapeutic strategy to enhance CRC response to immunotherapy. Finally, we developed a lipid nanoparticles (LNPs) and chemically modified small interfering RNAs (CMsiRNAs)‐based strategy to silence PCIF1 in vivo and found that this treatment significantly reduced tumor growth in mice. Our results therefore provide a proof‐of‐concept for tumor growth suppression using LNP‐CMsiRNA to silence target genes in cancer.     

Exploring the mechanism of Cassiae semen in regulating lipid metabolism through network pharmacology and experimental validation

Background: Multiple studies have assessed the role of Cassiae semen (CS) in regulating lipid metabolism. However, the mechanism of action of CS on non-alcoholic fatty liver disease (NAFLD) has seen rare scrutiny. Objective: The objective of this study was to explore the regulatory mechanism of CS on lipid metabolism in NAFLD. Methods: Components of CS ethanol extract (CSEE) were analyzed and identified using UPLC-Q-Orbirap HRMS. The candidate compounds of CS and its relative targets were extracted from the Traditional Chinese Medicine Systems Pharmacology, Swiss-Target-Prediction, and TargetNet web server. The Therapeutic Target Database, Genecards, Online Mendelian Inheritance in Man, and DisGeNET were searched for NAFLD targets. Binding affinity between potential core components and key targets was established employing molecular docking simulations. After that, free fatty acid (FFA)-induced HepG2 cells were used to further validate part of the network pharmacology results. Results: Six genes, including Caspase 3 (CASP3), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA), epidermal growth factor receptor (EGFR), and amyloid β (A4) precursor protein (APP) were identified as key targets. The mitogen-activated protein kinase (MAPK) signaling pathway was found to associate closely with CS’s effect on NAFLD. Per molecular docking findings, toralactone and quinizarin formed the most stable combinations with hub genes. About 0.1 (vs. FFA, P<0.01) and 0.2 (vs. FFA, P<0.05) mg/ml CSEE decreased lipid accumulation in vitro by reversing the up-regulation of CASP3, EGFR, and APP and the down-regulation of PIK3CA. Conclusion: CSEE can significantly reduce intracellular lipid accumulation by modulating the MAPK signaling pathway to decrease CASP3 and EGFR expression.