Lan Yao

Abstract Precise resection of orbital tumors is a critically important but elusive issue. Fluorescence imaging in the near‐infrared II window (NIR‐II) holds the potential to provide the surgeons with real‐time identification for orbital tumors. Here, for the first time, we evaluated the feasibility and clinical value of NIR‐II fluorescence imaging in orbital tumor surgery. To establish the method of NIR‐II fluorescence imaging for orbital tumors, we developed a NIR‐II fluorescence imaging system and indocyanine green (ICG) served as the fluorescent contrast agent. Twenty‐two patients diagnosed with orbital tumors and scheduled for standard‐of‐care surgery were enrolled in this study. Time‐course NIR‐II fluorescence imaging of two patients with superficial orbital tumors showed the optimum imaging time was 2 h post injection of ICG. Fifteen patients were allocated for diagnostic test, which showed that both the in situ and ex vivo NIR‐II fluorescence imaging showed better sensitivity and specificity than the surgeon judgment. In the feasibility trial of the remaining five patients, the surgeon encountered 34 suspicious regions and surgical decisions were changed nine times due to NIR‐II fluorescence imaging. The resultant seven additional resections were justified by histopathology and the two conservative treatments did not result in recurrence. Based on these findings, we suggested that ICG‐based NIR‐II fluorescence imaging was feasible to guide precise resection of orbital tumors. A future randomized controlled trial with a larger cohort is encouraged to further verify the clinical value.

Mitochondrial dysfunction is considered highly related to the development and progression of diseases, including cancer, metabolism disturbance, and neurodegeneration. Traditional pharmacological approach for mitochondrial dysfunction treatment has off-target and dose-dependent side effects, which leads to the emergence of mitochondrial gene therapy by regulating coding or noncoding genes by using nucleic acid sequences such as oligonucleotides, peptide nucleic acids, rRNA, siRNA, etc. To avoid size heterogeneity and potential cytotoxicity of the traditional delivery vehicle like liposome, framework nucleic acids have shown promising potentials. First, special spatial structure like tetrahedron allows entry into cells without transfection reagents. Second, the nature of nucleic acid provides the editability of framework structure, more sites and methods for drug loading and targeted sequences linking, providing efficient transportation and accurate targeting to mitochondria. Third, controllable size leads a possibility to go through biological barrier such as the blood-brain barrier, reaching the central nervous system to reverse mitochondria-related neurodegeneration. In addition, it's biocompatibility and physiological environmental stability open up the possibility of in vivo treatments for mitochondrial dysfunction. Furthermore, we discuss the challenges and opportunities of framework nucleic acids-based delivery systems in mitochondrial dysfunction.

Prime editing (PE), a novel “search-and-replace” genome editing technology, demonstrates significant potential for crop genetic improvement due to its precision and versatility. However, since its initial application in plants, PE technology has consistently faced challenges of low and variable editing efficiency, representing a major bottleneck hindering its broader application. Therefore, this study conducted a systematic review following the PRISMA 2020 guidelines. We systematically searched databases—Web of Science, PubMed, and Google Scholar—for studies published up to June 2025 focusing on enhancing PE performance in crops. After a rigorous screening process, 38 eligible primary research articles were ultimately included for comprehensive analysis. Our analysis revealed that early PE systems such as PE2 could perform diverse edits, including all 12 base substitutions and small insertions or deletions (indels), but their efficiency was highly variable across species, targets, and edit types. To overcome this bottleneck, researchers developed four major optimization strategies: (1) engineering core components such as Cas9, reverse transcriptase (RT), and editor architecture; (2) enhancing expression and delivery via optimized promoters and vectors; (3) improving reaction processes by modulating DNA repair pathways or external conditions; and (4) enriching edited events through selectable or visual markers. These advancements broadened PE’s targeting scope with novel Cas9 variants and enabled complex, kilobase-scale DNA insertions and rearrangements. The application of PE technology in plants has evolved from basic functional validation, through systematic optimization for enhanced efficiency, to advanced stages of functional expansion. This review charts this trajectory and clarifies the key strategies driving these advancements. We posit that future breakthroughs will increasingly depend on synergistically integrating these strategies to enable the efficient, precise, and predictable application of PE technology across diverse crops and complex breeding objectives. This study provides an important theoretical framework and practical guidance for subsequent research and application in this field.

Purpose: To explore the pathological differences in orbital adipose/connective tissue between active and inactive thyroid eye disease (TED) subjects and their correlations with clinical characteristics. Methods: Orbital adipose/connective tissue samples from 42 TED subjects (20 active, 22 inactive) were collected during decompression surgery. We analyzed cytokine expression, inflammatory cell infiltration, inherent cell populations, and interstitial changes by Luminex and histopathology. Correlations were analyzed using Pearson and Spearman correlation analyses. Results: Among the 108 cytokines detected, active TED exhibited elevated platelet endothelial cell adhesion molecule 1 (PECAM-1), interleukin-23 (IL-23), a proliferation-inducing ligand (APRIL), IL-6, C-C motif chemokine ligand 2 (CCL2), β-nerve growth factor (NGF), and lower CCL21 and CCL5. The extent of infiltration by helper T (Th) cells and monocytes was significantly greater in the active group than in the inactive group. Adipocyte density was significantly elevated in active TED, whereas fibrosis was more prominent in inactive TED. Fifteen cytokines were significantly associated with inflammatory cell infiltration, with IL-16 showing the strongest correlations with T cells. Ten cytokines showed significant positive correlations with fibrosis. Four cytokines (IL-6, PECAM-1, IL-23 and transforming growth factor β1), Th cell infiltration and adipocyte density were significantly positively correlated with clinical activity score (CAS). Sixteen cytokines, along with adipocyte density, were significantly positively correlated with disease severity of TED. Conclusions: The orbital adipose/connective tissues of active and inactive TED subjects showed significant differences in terms of cytokines, inflammatory cells infiltration, inherent cells and interstitium. These pathological changes were correlated with clinical characteristics of TED.

Primary high-grade lacrimal gland (LG) mucoepidermoid carcinoma (MEC) is a rare condition that presents diagnostic and treatment challenges. In this study, we aimed to elucidate the diagnosis, treatment, and mutational landscape of high-grade LG MEC. We reviewed clinical symptoms, radiological images, treatment, prognosis, histopathology, and mutational landscape of 20 patients with high-grade LG MEC. Primary clinical presentation of high-grade LG MEC was proptosis (85%) with a low incidence of ocular pain (20%). CT scans showed frequent bone destruction (89.5%) and calcification (73.7%). MRI revealed hypointense areas on T2-weighted imaging (WI) in 85% of lesions and non-enhanced areas on contrast-enhanced T1WI in 95% of cases. All 20 patients with primary high-grade LG MEC underwent surgery and were stratified into 5 treatment groups. Multi-group analysis showed only the complete resection plus adjuvant radiotherapy group had significantly better RFS than the complete resection alone group (both P = 0.0016), with no significant OS differences across groups. The rates of recurrence, metastasis, and mortality for patients in T4 stage were 77.8%, 71.4%, and 100%, respectively, while those in stages T1-3 were 25%, 75%, and 62.5%. Log-rank tests demonstrated superior long-term RFS and OS in T1–3 patients (P < 0.05), whereas Gehan-Breslow-Wilcoxon tests yielded non-significant results. Whole-exome sequencing of tumors and adjacent normal tissues from 3 patients showed TP53 as the only consistent driver gene with missense mutations in all samples. Additionally, EGFR, DOCK2, GAN11, AKAP9, and SMC4 were identified as driver genes in 2 patients. High-grade LG MEC predominantly manifested as painless exophthalmos and the characteristic imaging included calcification, bone destruction, hypointense areas on T2WI, and non-enhanced areas on contrast-enhanced T1WI. Adjuvant radiotherapy after complete resection reduced recurrence and improved RFS but did not significantly elevate the overall survival rate of primary high-grade LG MEC patients. Prognosis is especially poor for T4 stage. Potential somatic variants identified within this small exploratory cohort, including TP53, EGFR, DOCK2, GAN11, AKAP9, and SMC4 may represent the potential therapeutic targets. Nevertheless, their clinical and prognostic relevance requires rigorous validation in larger independent patient cohorts.