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Naphthalene diimides (NDI) are widely serving as the skeleton to construct electron transport materials (ETMs) for optoelectronic devices. However, most of the reported NDI‐based ETMs suffer from poor interfaces with the perovskite which deteriorates the carrier extraction and device stability. Here, a representative design concept for editing the peripheral groups of NDI molecules to achieve multifunctional properties is introduced. The resulting molecule 2,7‐bis(2,2,3,3,4,4,4‐heptafluorobutyl)benzo[lmn][3,8]phenanthroline‐1,3,6,8(2H,7H)‐tetraone (NDI‐C4F) incorporated with hydrophobic fluorine units contributes to the prevention of excessive molecular aggregation, the improvement of surface wettability and the formation of strong chemical coordination with perovskite precursors. All these features favor retarding the perovskite crystallization and achieving superior buried interfaces, which subsequently promote charge collection and improve the structural compatibility between perovskite and ETMs. The corresponding PSCs based on low‐temperature processed NDI‐C4F yield a record efficiency of 23.21%, which is the highest reported value for organic ETMs in n‐i‐p PSCs. More encouragingly, the unencapsulated devices with NDI‐C4F demonstrate extraordinary stability by retaining over 90% of their initial PCEs after 2600 h in air. This work provides an alternative molecular strategy to engineer the buried interfaces and can trigger further development of organic ETMs toward reliable PSCs. A representative design concept for editing the peripheral groups of naphthalene diimides (NDI) molecules is proposed. The fluorinate NDI (NDI‐C4F) contributes to the prevention of excessive molecular aggregation, the improvement of surface wettability, and the formation of strong chemical coordination with perovskite precursors.

Purpose To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization. Methods In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy. Results SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models. Conclusion Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.

The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. The integration of novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, and artificial intelligence have significantly expedited the development of groundbreaking peptide-based drugs, effectively addressing the obstacles associated with their character, such as the rapid clearance and degradation, necessitating subcutaneous injection leading to increasing patient discomfort, and ultimately advancing translational research efforts. Peptides are presently employed in the management and diagnosis of a diverse array of medical conditions, such as diabetes mellitus, weight loss, oncology, and rare diseases, and are additionally garnering interest in facilitating targeted drug delivery platforms and the advancement of peptide-based vaccines. This paper provides an overview of the present market and clinical trial progress of peptide-based therapeutics, delivery platforms, and vaccines. It examines the key areas of research in peptide-based drug development through a literature analysis and emphasizes the structural modification principles of peptide-based drugs, as well as the recent advancements in screening, design, and delivery technologies. The accelerated advancement in the development of novel peptide-based therapeutics, including peptide-drug complexes, new peptide-based vaccines, and innovative peptide-based diagnostic reagents, has the potential to promote the era of precise customization of disease therapeutic schedule.

Unlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) are considered non-conserved. Although lncRNAs have been shown to function in diverse pathophysiological processes in mice, it remains largely unknown whether human lncRNAs have such in vivo functions. Here, we describe an integrated pipeline to define the in vivo function of non-conserved human lncRNAs. We first identify lncRNAs with high function potential using multiple indicators derived from human genetic data related to cardiometabolic traits, then define lncRNA’s function and specific target genes by integrating its correlated biological pathways in humans and co-regulated genes in a humanized mouse model. Finally, we demonstrate that the in vivo function of human-specific lncRNAs can be successfully examined in the humanized mouse model, and experimentally validate the predicted function of an obesity-associated lncRNA, LINC01018, in regulating the expression of genes in fatty acid oxidation in humanized livers through its interaction with RNA-binding protein HuR. Majority of human long non-coding RNAs (lncRNAs) are not conserved in mouse. Here the authors identify metabolic trait-associated lncRNA genes and show a functional role of a non-conserved human lncRNA, LINC01018, in lipid metabolism using a humanized mouse model.

Due to the limited availability of land resources, offshore wind turbines have become a crucial technology for the development of deep-water renewable energy. The multi-floating body platform, characterized by its shallow draft and main body located near the sea surface, is prone to significant motion in marine environments. The proper chamfering of the heave plate can effectively enhance its resistance during wave action, thereby improving the stability of the floating platform. The optimal chamfer angle is 35°. Considering the complexity of the floating body’s motion response, this study focuses on the damping characteristics of the heave plate with 35° chamfered perforations. Using the NREL 5 MW three-column semi-submersible floating wind turbine platform as the research model, the hydrodynamic characteristics of the floating body with a perforated heave plate are systematically studied through theoretical analysis, numerical simulation, and physical tests. The amplitude of vertical force under various working conditions is measured. Through theoretical analysis, the additional mass coefficient and additional damping coefficient for different working conditions and models are determined. The study confirms that the heave plate with 35° chamfered perforations significantly reduces heave in the multi-floating body.

Background Static carcinoembryonic antigen (CEA) levels are well‑established prognostic markers in patients with gastric cancer, but the significance of their dynamic trajectories over time has rarely been reported. Methods We analysed the perioperative CEA levels (presurgery, early postsurgery, and late postsurgery) of 578 gastric cancer patients who underwent curative resection, with a median follow-up of 29 months. We used the entire cohort for k-means clustering. Survival differences between clusters were assessed using Kaplan–Meier analysis and Cox regression. Results Of the 578 patients, 15.57% exhibited elevated CEA levels before surgery (median 2.07 ng/mL), which then decreased to 3.29% (median 1.74 ng/mL) after surgery. However, after six months, a slight rebound was observed (18.51% elevated, median 2.98 ng/mL). K-means clustering identified three CEA trajectories: high, medium, and low (Calinski–Harabasz index: 358). Survival analysis demonstrated that higher CEA trajectories were associated with worse disease-free survival (DFS) and overall survival (OS). With the low cluster as a reference, multivariate Cox regression analysis revealed that a higher CEA trajectory was an independent prognostic factor, with an elevated risk in the high cluster (HR 2.64, 95% CI: 1.37-5.0), indicating that the high cluster had more than twice the mortality risk of the low cluster and that the medium cluster had a moderately increased mortality risk (HR 1.69, 95% CI: 1.0-2.85). Conclusion Higher CEA trajectories are associated with a worse prognosis, highlighting the importance of enhanced monitoring for this group of patients. Highlights A machine learning-powered trajectory clustering algorithm employed. The trajectory cluster classification demonstrates a strong correlation with both disease-free survival and overall survival.

Background Carbohydrate Antigen 125 (CA125), a tumor-associated glycoprotein, is an established prognostic marker in gastric cancer. However, the trajectory of CA125 levels incorporating dynamic changes over time have not been investigated. Methods CA125 levels were collected during the first year of treatment to form individual trajectories and grouped using the unsupervised K-means algorithm. Cox proportional hazards model assessed the association between trajectory groups and overall survival (primary outcome). Results A total of 1,015 patients were included, covering stages I-IV. 7,347 CA125 tests were conducted, including 1,638 preoperatively and 5,709 postoperatively. The median CA125 trajectory exhibited a \"rise-decline\" pattern, with preoperative levels of 11.0 U/ml, followed by a temporary peak of 22.98 U/ml in the first quarter post-surgery, and subsequently declines to 12.21 U/ml in the second quarter and 10.90 U/ml at six months post-surgery. The unsupervised K-means machine learning identified 4 latent patterns of trajectories ranging at different levels. Trajectories in higher-level groups were significantly associated with worse survival outcomes: Low ( n  = 309, reference), Medium ( n  = 390, HR = 1.75, p  = 0.006), High ( n  = 238, HR = 4.66, p  < 0.001), and Ultra High ( n  = 78, HR = 17.9, p  < 0.001). Subgroup analysis revealed that across all stages, the survival risks in the High and Ultra High trajectory groups were consistently higher compared to the Low group. Multivariable Cox proportional hazards model confirmed trajectory as an independent prognostic factor. In comparative Cox analysis, models with trajectory (c-index 0.74–0.81) showed superior efficacy than models with static values (c-index 0.59–0.66). Conclusion We identified the distinct latent patterns of CA125 trajectory dynamics during the initial years of disease course. These patterns exhibited robust independent prognostic value. Highlights 1. First comprehensive study on CA125 trajectories in gastric cancer. 2. Large cohort, 1,015 patients, 7,347 CA125 tests, reliable results. 3. Novel unsupervised clustering algorithm, eliminating potential biases introduced by human judgment. 4. Robust prognostic value beyond tumor stage.

Growing evidence links human long noncoding RNAs (lncRNAs) to metabolic disease pathogenesis, yet no FDA-approved drugs target human lncRNAs. Most human lncRNAs lack conservation in other mammals, complicating efforts to define their roles and identify therapeutic targets. Here, we leveraged the concept of functionally conserved lncRNAs (FCLs)-- lncRNAs that share function despite no sequence similarity--to develop a framework for identifying human lncRNAs as therapeutic targets for metabolic disorders. We used expression quantitative trait loci mapping and functional conservation analyses to pinpoint human lncRNAs influenced by disease-associated SNPs and with potential functionally conserved mouse equivalents. We identified human and mouse GULLs (glucose and lipid lowering), which regulate glucose and lipid metabolism by binding CRTC2, thereby modulating gluconeogenic genes via CREB and lipogenic genes via SREBP1. Despite their lack of sequence similarity, both lncRNAs demonstrated similar metabolic effects in obese mice, with more pronounced benefits from long-term activation. To identify druggable sites, we mapped GULLs' binding motifs to CRTC2 (termed GULFs). Standalone human GULF, an RNA oligomer resembling FDA-approved siRNAs, significantly improved glucose and lipid levels in obese mice. This framework highlights functionally conserved human lncRNAs as promising therapeutic targets, exemplified by GULLs' potential as a glucose- and lipid-lowering therapeutic.

Growing evidence links human long noncoding RNAs (lncRNAs) to metabolic disease pathogenesis, yet no FDA-approved drugs target human lncRNAs. Most human lncRNAs lack conservation in other mammals, complicating efforts to define their roles and identify therapeutic targets. Here, we leveraged the concept of functionally conserved lncRNAs (FCLs) — lncRNAs that share function despite no sequence similarity — to develop a framework for identifying human lncRNAs as therapeutic targets for metabolic disorders. We used expression quantitative trait loci mapping and functional conservation analyses to pinpoint human lncRNAs influenced by disease-associated SNPs and with potential functionally conserved mouse equivalents. We identified human and mouse GULLs (glucose and lipid lowering), which regulate glucose and lipid metabolism by binding CRTC2, thereby modulating gluconeogenic genes via CREB and lipogenic genes via SREBP1. Despite their lack of sequence similarity, both lncRNAs demonstrated similar metabolic effects in obese mice, with more pronounced benefits from long-term activation. To identify druggable sites, we mapped GULLs’ binding motifs to CRTC2 (termed GULFs). Standalone human GULF, an RNA oligomer resembling FDA-approved siRNAs, significantly improved glucose and lipid levels in obese mice. This framework highlights functionally conserved human lncRNAs as promising therapeutic targets, exemplified by GULLs’ potential as a glucose- and lipid-lowering therapeutic.