Superoxide Anion-Mediated Afterglow Mechanism-Based Water-Soluble Zwitterion Dye Achieving Renal-Failure Mice Detection.

Afterglow materials-based biological imaging has promising application prospects, due to negligible background. However, currently available afterglow materials mainly include inorganic materials as well as some organic nanoparticles, which are difficult to translate to the clinic, resulting from non-negligible metabolic toxicity and even leakage risk of inorganic heavy metals. Although building small organic molecules could solve such obstacles, organic small molecules with afterglow ability are extremely scarce, especially with a sufficient renal metabolic capacity. To address these issues, herein, we designed water-soluble zwitterion Cy5-NF with renal metabolic capacity and afterglow luminescence, which relied on an intramolecular cascade reaction between superoxide anion (O2•-, instead of 1O2) and Cy5-NF to release afterglow luminescence. Of note, compared with different reference contrast agents, zwitterion Cy5-NF not only had excellent afterglow properties but also had a rapid renal metabolism rate (half-life period, t1/2, around 10 min) and good biocompatibility. Unlike prior afterglow nanosystems possessing a large size, for the first time, zwitterion Cy5-NF has achieved the construction of water-soluble renal metabolic afterglow contrast agents, which showed higher sensitivity and signal-to-background ratio in afterglow imaging than fluorescence imaging for the kidney. Moreover, zwitterion Cy5-NF had a longer kidney retention time in renal-failure mice (t1/2 more than 15 min). More importantly, zwitterion Cy5-NF can be metabolized very quickly even in severe renal-failure mice (t1/2 around 25-30 min), which greatly improved biosecurity. Therefore, we are optimistic that the O2•--mediated afterglow mechanism-based water-soluble zwitterion Cy5-NF is very promising for clinical application, especially rapid detection of kidney failure.

Orderly Self-Assembly of Organic Fluorophores for Sensing and Imaging.

Fluorescence imaging utilizing traditional organic fluorophores is extensively applied in both cellular and in vivo studies. However, it faces significant obstacles, such as low signal-to-background ratio (SBR) and spurious positive/negative signals, primarily due to the facile diffusion of these fluorophores. To cope with this challenge, orderly self-assembled functionalized organic fluorophores have gained significant attention in the past decades. These fluorophores can create nanoaggregates via a well-ordered self-assembly process, thus prolonging their residency time within cells and in vivo settings. The development of self-assembled-based fluorophores is an emerging field, and as such, in this review, we present a summary of the progress and challenges of self-assembly fluorophores, focusing on their development history, self-assembly mechanisms, and biomedical applications. We hope that the insights provided herein will assist scientists in further developing functionalized organic fluorophores for in situ imaging, sensing, and therapy.

In situ orderly self-assembly strategy affording NIR-II-J-aggregates for in vivo imaging and surgical navigation.

J-aggregation, an effective strategy to extend wavelength, has been considered as a promising method for constructing NIR-II fluorophores. However, due to weak intermolecular interactions, conventional J-aggregates are easily decomposed into monomers in the biological environment. Although adding external carriers could help conventional J-aggregates stabilize, such methods still suffer from high-concentration dependence and are unsuitable for activatable probes design. Besides, these carriers-assisted nanoparticles are risky of disassembly in lipophilic environment. Herein, by fusing the precipitated dye (HPQ) which has orderly self-assembly structure, onto simple hemi-cyanine conjugated system, we construct a series of activatable, high-stability NIR-II-J-aggregates which overcome conventional J-aggregates carrier's dependence and could in situ self-assembly in vivo. Further, we employ the NIR-II-J-aggregates probe HPQ-Zzh-B to achieve the long-term in situ imaging of tumor and precise tumor resection by NIR-II imaging navigation for reducing lung metastasis. We believe this strategy will advance the development of controllable NIR-II-J-aggregates and precise bioimaging in vivo.

Knockdown of ezrin suppresses the migration and angiogenesis of human umbilical vein endothelial cells in vitro / 华中科技大学学报（医学）（英德文版）

Progressive tumor growth is dependent on angiogenesis. The mechanisms by which endothelial cells (ECs) are incorporated to develop new blood vessels are not well understood. Recent studies reveal that the ezrin radixin moesin (ERM) family members are key regulators of cellular activities such as adhesion, morphogenetic change, and migration. We hypothesized that ezrin, one of the ERM family members, may play important roles in ECs organization during angiogenesis, and new vessels formation in preexisting tissues. To test this hypothesis, in this study, we investigated the effects of ezrin gene silencing on the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs were transfected with plasmids with ezrin-targeting short hairpin RNA by using the lipofectamine-2000 system. Wound assay in vitro and three-dimensional culture were used to detect the migration and angiogenesis capacity of HUVECs. The morphological changes of transfected cells were observed by confocal and phase contrast microscopy. Our results demonstrated that the decreased expression of ezrin in HUVECs significantly induced the morphogenetic changes and cytoskeletal reorganization of the transfected cells, and also reduced cell migration and angiogenesis capacity in vitro, suggesting that ezrin play an important role in the process of HUVECs migration and angiogenesis.

Knockdown of ezrin suppresses the migration and angiogenesis of human umbilical vein endothelial cells in vitro / 华中科技大学学报（医学）（英德文版）

Progressive tumor growth is dependent on angiogenesis. The mechanisms by which endothelial cells (ECs) are incorporated to develop new blood vessels are not well understood. Recent studies reveal that the ezrin radixin moesin (ERM) family members are key regulators of cellular activities such as adhesion, morphogenetic change, and migration. We hypothesized that ezrin, one of the ERM family members, may play important roles in ECs organization during angiogenesis, and new vessels formation in preexisting tissues. To test this hypothesis, in this study, we investigated the effects of ezrin gene silencing on the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs were transfected with plasmids with ezrin-targeting short hairpin RNA by using the lipofectamine-2000 system. Wound assay in vitro and three-dimensional culture were used to detect the migration and angiogenesis capacity of HUVECs. The morphological changes of transfected cells were observed by confocal and phase contrast microscopy. Our results demonstrated that the decreased expression of ezrin in HUVECs significantly induced the morphogenetic changes and cytoskeletal reorganization of the transfected cells, and also reduced cell migration and angiogenesis capacity in vitro, suggesting that ezrin play an important role in the process of HUVECs migration and angiogenesis.

Influence of insulin resistance on long-term outcomes in patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Insulin resistance (IR) is significantly associated with coronary artery disease and cardiovascular events in patients with or without type 2 diabetes mellitus. This study aimed to evaluate the influence of IR on long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation.</p><p><b>METHODS</b>A total of 467 consecutive patients undergoing SES-based PCI were divided into IR group (n = 104) and non-IR group (n = 363). The patients were followed up for one year. The rate of major adverse cardiac events (MACEs) including death, non-fatal myocardial infarction and recurrent angina pectoris was compared by the log-rank test, and the independent risk factors were identified by the Cox regression analysis.</p><p><b>RESULTS</b>MACEs occurred more frequently, and cumulative survival rate was lower in the IR group than in the non-IR group during the follow-up (all P < 0.05). IR was an independent risk factor for the occurrence of cardiac death and non-fatal myocardial infarction (OR = 2.76, 95%CI = 1.35 - 5.47, P = 0.034). Old age, diabetes, and multi-vessel disease were determinants for recurrent angina pectoris after PCI (P < 0.05). Subgroup analysis revealed that IR (OR = 3.35, 95%CI = 1.07 - 13.59, P = 0.013) and multi-vessel disease (OR = 2.19, 95%CI = 1.01 - 5.14, P = 0.044) were independent risk predictors for recurrent angina pectoris in patients with diabetes after PCI.</p><p><b>CONCLUSIONS</b>IR is associated with reduced MACE-free survival and remains an independent predictor for recurrent angina pectoris after PCI with SES implantation.</p>