Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Clathrin-mediated endocytosis (CME) is a critical process by which cells internalize macromolecular substances and initiate vesicle trafficking, serving as the foundation for many cellular activities. Central to this process are clathrin-coated structures (CCSs), which consist of clathrin-coated pits (CCPs) and clathrin plaques. While clathrin-coated pits are well-established in the study of endocytosis, clathrin plaques represent a more recently discovered but equally important component of this system. These plaques are large, flat, and extended clathrin-coated assemblies found on the cytoplasmic membrane. They are distinct from the more typical clathrin-coated pits in terms of their morphology, larger surface area, and longer lifespan. Recent research has revealed that clathrin plaques play roles that go far beyond endocytosis, contributing to diverse cellular processes such as cellular adhesion, mechanosensing, migration, and pathogen invasion. Unlike traditional clathrin-coated pits, which are transient and dynamic structures involved primarily in the internalization of molecules, clathrin plaques are more stable and extensive, often persisting for extended periods. Their extended lifespan suggests that they serve functions beyond the typical endocytic role, making them integral to various cellular processes. For instance, clathrin plaques are involved in the regulation of intercellular adhesion, allowing cells to better adhere to one another or to the extracellular matrix, which is crucial for tissue formation and maintenance. Furthermore, clathrin plaques act as mechanosensitive hubs, enabling the cell to sense and respond to mechanical stress, a feature that is essential for processes like migration, tissue remodeling, and even cancer progression. Recent discoveries have also highlighted the role of clathrin plaques in cellular signaling. These plaques can serve as scaffolds for signaling molecules, orchestrating the activation of various pathways that govern cellular behavior. For example, the recruitment of actin-binding proteins such as F-actin and vinculin to clathrin plaques can influence cytoskeletal dynamics, helping cells adapt to mechanical changes in their environment. This recruitment also plays a pivotal role in regulating cellular migration, which is crucial for developmental processes. Additionally, clathrin plaques influence receptor-mediated signal transduction by acting as platforms for the assembly of signaling complexes, thereby affecting processes such as growth factor signaling and cellular responses to extracellular stimuli. Despite the growing body of evidence that supports the involvement of clathrin plaques in a wide array of cellular functions, much remains unknown about the precise molecular mechanisms that govern their formation, maintenance, and turnover. For example, the factors that regulate the recruitment of clathrin and other coat proteins to form plaques, as well as the signaling molecules that coordinate plaque dynamics, remain areas of active research. Furthermore, the complex interplay between clathrin plaques and other cellular systems, such as the actin cytoskeleton and integrin-based adhesion complexes, needs further exploration. Studies have shown that clathrin plaques can respond to mechanical forces, with recent findings indicating that they act as mechanosensitive structures that help the cell adapt to changing mechanical environments. This ability underscores the multifunctional nature of clathrin plaques, which, in addition to their role in endocytosis, are involved in cellular processes such as mechanotransduction and adhesion signaling. In summary, clathrin plaques represent a dynamic and versatile component of clathrin-mediated endocytosis. They play an integral role not only in the internalization of macromolecular cargo but also in regulating cellular adhesion, migration, and signal transduction. While much has been learned about their structural and functional properties, significant questions remain regarding the molecular mechanisms that regulate their formation and their broader role in cellular physiology. This review highlights the evolving understanding of clathrin plaques, emphasizing their importance in both endocytosis and a wide range of other cellular functions. Future research is needed to fully elucidate the mechanisms by which clathrin plaques contribute to cellular processes and to better understand their implications for diseases, including cancer and tissue remodeling. Ultimately, clathrin plaques are emerging as crucial hubs that integrate mechanical, biochemical, and signaling inputs, providing new insights into cellular function and the regulation of complex cellular behaviors.

Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

RNA-binding proteins (RBPs) are ubiquitous components within cells, fulfilling essential functions in a myriad of biological processes. These proteins interact with RNA molecules to regulate gene expression at various levels, including transcription, splicing, transport, localization, translation, and degradation. Understanding the intricate network of RBP-RNA interactions is crucial for deciphering the complex regulatory mechanisms that govern cellular function and organismal development. Ultravidet (UV) cross-linking and immunoprecipitation (CLIP) stands out as a powerful approach designed to map the precise locations where RBPs bind to RNA. By using UV light to create covalent bonds between proteins and RNA, followed by immunoprecipitation to isolate the protein-RNA complexes, researchers can identify the direct targets of specific RBPs. The advent of high-throughput sequencing technologies has revolutionized CLIP, enabling the identification of not only the types but also the exact sequences of RNA bound by RBPs on a genome-wide scale. The evolution of CLIP has led to the development of specialized variants, each with unique features that address specific challenges and expand the scope of what can be studied. High-throughput sequencing CLIP (HITS-CLIP) was one of the first advancements, significantly increasing the throughput and resolution of RNA-protein interaction mapping. Photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) introduced the use of photoactivatable ribonucleosides to enhance cross-linking efficiency and specificity, reducing background noise and improving the detection of low-abundance RNA-protein interactions. Individual-nucleotide resolution CLIP (iCLIP) further refined the technique, achieving unprecedented precision by resolving individual nucleotides involved in RBP binding, which is particularly valuable for studying the fine details of RNA structure and function. Despite the remarkable progress, there remains room for improvement in CLIP technology. Researchers continue to seek methods to increase sensitivity, reduce technical variability, and improve the reproducibility of results. Advances in sample preparation, data analysis algorithms, and computational tools are critical for addressing these challenges. Moreover, the application of CLIP to more diverse biological systems, including non-model organisms and clinical samples, requires the development of tailored protocols and the optimization of existing ones. Looking forward, the field of RNA biology is poised to benefit greatly from ongoing innovations in CLIP technology. The exploration of non-canonical RNA-protein interactions, such as those involving long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), promises to reveal new layers of cellular regulation and may lead to the discovery of novel therapeutic targets. Furthermore, integrating CLIP data with other omics approaches, such as proteomics and metabolomics, will provide a more comprehensive understanding of the dynamic interplay between RNA and its binding partners within the cell. In conclusion, the continuous refinement and expansion of CLIP techniques have not only deepened our knowledge of RNA biology but have also opened up new avenues for investigating the molecular underpinnings of health and disease. As the technology matures, it is expected to play an increasingly pivotal role in both basic and applied research, contributing to the advancement of medical science and biotechnology.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal