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The use of ligand conjugation onto nanoparticle surfaces as an active targeting strategy has gained significant attention in the pursuit of improving tumor‐specific delivery and retention. However, the chemical conjugation of targeting moieties often induces alterations in the physicochemical properties of nanoparticles, including size, conformation, charge‐to‐mass ratio, and hydrophilicity/lipophilicity, resulting in unexpected biodistribution and pharmacokinetic profiles. Here, the enhanced active targeting efficiency achieved by integrating cyclic arginine–glycine–aspartic acid (cRGD) peptides onto ultrasmall nanocarrier H‐dot while preserving its essential physicochemical and pharmacokinetic attributes is investigated. The resulting cRGD/H‐dots demonstrate improved cellular uptake via integrin αvβ3 receptors, accompanied by negligible cytotoxicity. Notably, the active targeting efficacy of cRGD/H‐dots compared to unmodified H‐dots (1.2%ID/g, two‐fold increase) is quantitatively evaluated, validated through fluorescence imaging and histological analysis. The findings highlight that cRGD/H‐dots offer enhanced tumor targetability and prolonged tumoral retention while maintaining active renal clearance of unbound molecules. [ABSTRACT FROM AUTHOR]

Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single‐cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learning algorithms to establish a prognostic and immunotherapeutic signature (PIS) for LUAD. In multiple cohorts, PIS outperformed 144 previously published signatures in predicting LUAD prognosis. Importantly, PIS reliably predicted genomic alterations, chemotherapy sensitivity and immunotherapy responses. Immunohistochemistry validated lower expression of immune markers in the low‐PIS group, while in vitro experiments underscored the role of the key gene PSMB7 in LUAD progression. In conclusion, PIS represents a novel biomarker facilitating the selection of suitable LUAD patients for immunotherapy, ultimately improving prognosis and guiding clinical decisions. [ABSTRACT FROM AUTHOR]

Fusarium wilt (FW) is widespread in global cotton production, but the mechanism underlying FW resistance in superior‐fiber‐quality Sea Island cotton is unclear. This study reveals that FW resistance has been the target of genetic improvement of Sea Island cotton in China since the 2010s. The key nonsynonymous single nucleotide polymorphism (SNP, T/C) of gene Gbar_D03G001670 encoding protein phosphatase 2C 80 (PP2C80) results in an amino acid shift (L/S), which is significantly associated with FW resistance of Sea Island cotton. Silencing GbPP2C80 increases FW resistance in Sea Island cotton, whereas overexpressing GbPP2C80 reduces FW resistance in Arabidopsis. GbPP2C80 and GbWAKL14 exist synergistically in Sea Island cotton accessions with haplotype forms "susceptible–susceptible" (TA) and "resistant–resistant" (CC), and interact with each other. CRISPR/Cas9‐mediated knockout of GbWAKL14 enhances FW and Verticillium wilt (VW) resistance in upland cotton and overexpression of GbWAKL14 and GbPP2C80 weakens FW and VW resistance in Arabidopsis. GbPP2C80 and GbWAKL14 respond to FW and VW by modulating reactive oxygen species (ROS) content via affecting MPK3 expression. In summary, two tandem genes on chromosome D03, GbPP2C80, and GbWAKL14, functions as cooperative negative regulators in cotton wilt disease defense, providing novel genetic resources and molecular markers for the development of resistant cotton cultivars. [ABSTRACT FROM AUTHOR]

Targeting the alpha-v beta-3 integrin receptor holds promise for active targeting in cancer therapy and imaging diagnostics. Cyclic (arginine-glycine-aspartate-phenylalanine-lysine), an arginylglycylaspartic acid tumor-targeting peptide, has shown efficient selective binding to the alpha-v beta-3 integrin receptor, making it a highly effective ligand. Its potential for active targeting in drug delivery has garnered significant attention, leading to extensive research and development efforts. This paper provides a comprehensive review of the application of the cyclic (arginine-glycine-aspartate-phenylalanine-lysine) in nanoparticle-mediated drug delivery systems, aiming to serve as a valuable reference for the expedited development of active targeting formulations. This article explores the utilization of cyclic (arginine-glycine-aspartate-phenylalanine-lysine) as a targeting ligand in these systems and discusses its role, either as the sole ligand or in combination with others, in enhancing the precision of drug delivery to specific lesion sites, with a primary focus on tumors. This paper describes the current status of cyclic (arginine-glycine-aspartate-phenylalanine-lysine)-modified nanoparticles in various carrier materials for targeted therapy, molecular imaging, cytotoxic peptide delivery, photosensitizer delivery, and modified biomaterials. The strategic manipulation of drug distribution and pharmacokinetic properties aims to optimize therapeutic outcomes while minimizing systemic side effects, showcasing the potential of cyclic (arginine-glycine-aspartate-phenylalanine-lysine)-modified nanoparticle systems in advancing precision medicine. [ABSTRACT FROM AUTHOR]

SUMMARY: Salinity is frequently mentioned as a major constraint in worldwide agricultural production. Lint percentage (LP) is a crucial yield‐component in cotton lint production. While the genetic factors affect cotton yield in saline soils are still unclear. Here, we employed a recombinant inbred line population in upland cotton (Gossypium hirsutum L.) and investigated the effects of salt stress on five yield and yield component traits, including seed cotton yield per plant, lint yield per plant, boll number per plant, boll weight, and LP. Between three datasets of salt stress (E1), normal growth (E2), and the difference values dataset of salt stress and normal conditions (D‐value), 87, 82, and 55 quantitative trait loci (QTL) were detectable, respectively. In total, five QTL (qLY‐Chr6‐2, qBNP‐Chr4‐1, qBNP‐Chr12‐1, qBNP‐Chr15‐5, qLP‐Chr19‐2) detected in both in E1 and D‐value were salt related QTL, and three stable QTL (qLP‐Chr5‐3, qLP‐Chr13‐1, qBW‐Chr5‐5) were detected both in E1 and E2 across 3 years. Silencing of nine genes within a stable QTL (qLP‐Chr5‐3) highly expressed in fiber developmental stages increased LP and decreased fiber length (FL), indicating that multiple minor‐effect genes clustered on Chromosome 5 regulate LP and FL. Additionally, the difference in LP caused by Gh_A05G3226 is mainly in transcription level rather than in the sequence difference. Moreover, silencing of salt related gene (GhDAAT) within qBNP‐Chr4‐1 decreased salt tolerance in cotton. Our findings shed light on the regulatory mechanisms underlining cotton salt tolerance and fiber initiation. Significance Statement: Our study provided important gene resources for salt tolerance improvement of cotton, and shed light on the regulatory mechanisms underlining plant salt tolerance. [ABSTRACT FROM AUTHOR]