An innovative fluorescent probe based on dicyanoisoflurone derivatives for differential detection of Hg2+ and Cu2+ and its applications in bacteria, cell imaging and food analysis.

BACKGROUND: Heavy metal pollution has become one of the world's most important environmental pollution, especially Hg2+ is enriched, it is easy to enter the human body through the food chain, bind to the sulfhydryl group in the protein, cause mercury poisoning. Traditional methods for detecting Hg2+ have obvious drawbacks, such as poor selectivity and long detection time. Fluorescence detection has attracted attention because of its good sensitivity and specificity detection ability. In previously reported probes for detecting Hg2+, Cu2+ often interferes. Therefore, it is of great practical significance to synthesize a fluorescent probe that can distinguish between Hg2+ and Cu2+. RESULTS: We have successfully synthesized the probe DFS, a fluorescent probe that can differentially detect Hg2+ and Cu2+, and the probe DFS has good selectivity and anti-interference ability for Hg2+ and Cu2+. The fluorescence intensity at 530 nm increased rapidly when Hg2+ was detected; during the Cu2+ detection, the fluorescence intensity at 636 nm gradually decreased, fluorescence quenching occurred, and the detection limits of Hg2+ and Cu2+ were 7.29 × 10-9 M and 2.13 × 10-9 M, respectively. Through biological experiments, it was found that probe DFS can complete the fluorescence imaging of Hg2+ and Cu2+ in Staphylococcus aureus and HUVEC cells, which has certain research value in the field of environmental monitoring and microbiology, and the probe DFS has low cytotoxicity, so it also has broad application prospects in the field of biological imaging. In addition, the probe DFS also has good applicability for Hg2+ and Cu2+ detection in actual samples. SIGNIFICANCE AND NOVELTY: This is a fluorescent probe that can distinguish between Hg2+ and Cu2+, the fluorescence emission peak appears at 530 nm when Hg2+ is detected; when detecting Cu2+, fluorescence quenching occurs at 636 nm, the fluorescence emission peak distance between Hg2+ and Cu2+ differs by 106 nm. This reduces mutual interference between Hg2+ and Cu2+ during detection, it provides a new idea for the detection of Hg2+ and Cu2+.

An innovative near-infrared fluorescent probe with FRET effect for the continuous detection of Zn2+ and PPi with high sensitivity and selectivity, and its application in bioimaging.

As the second most abundant transition metal element in the human body, zinc ions play an important role in the normal growth and development of the human body. We have successfully synthesized a near-infrared fluorescent probe with FRET effect for the detection of Zn2+. Probe DR6G has good selectivity and anti-interference ability for Zn2+. When Zn2+ is added to the probe DR6G solution, it responds completely within seconds, releasing red fluorescence with a detection limit of 2.02 × 10-8 M. As the main product of ATP hydrolysis, PPi is indispensable in various metabolic activities in cells and the human body. Due to the strong binding ability of Zn2+ and PPi, it is easy to form ZnPPi precipitation, so we added PPi to the solution to complete the Zn2+ detection, and realized the continuous detection of PPi, and the detection limit was 2.06 × 10-8 M. Since Zn2+ and PPi play an important role in vivo, it is of great practical significance to design and synthesize a fluorescent probe that can continuously detect Zn2+ and PPi. Biological experiments have shown that the probe DR6G has low cytotoxicity and can complete the detection of exogenous Zn2+ and PPi in cells and living mice in vitro. Bacterial experiments have shown that the DR6G probe also has certain research value in the field of environmental monitoring and microbiology. Due to the constant variation of the fluorescence signals of Zn2+ and PPi during detection, we designed the logic gate program. In practical applications, the probe DR6G can quantitatively detect Zn2+ in zinc-containing oral liquids and qualitatively detect PPi in toothpaste.

Stromal cells in the tumor microenvironment: accomplices of tumor progression?

The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), and cellular components include cancer cells and non-malignant cells such as immune cells and stromal cells. These three types of cells establish complex signals in the body and further influence tumor genesis, development, metastasis and participate in resistance to anti-tumor therapy. It has attracted scholars to study immune cells in TME due to the significant efficacy of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T (CAR-T) in solid tumors and hematologic tumors. After more than 10 years of efforts, the role of immune cells in TME and the strategy of treating tumors based on immune cells have developed rapidly. Moreover, ICI have been recommended by guidelines as first- or second-line treatment strategies in a variety of tumors. At the same time, stromal cells is another major class of cellular components in TME, which also play a very important role in tumor metabolism, growth, metastasis, immune evasion and treatment resistance. Stromal cells can be recruited from neighboring non-cancerous host stromal cells and can also be formed by transdifferentiation from stromal cells to stromal cells or from tumor cells to stromal cells. Moreover, they participate in tumor genesis, development and drug resistance by secreting various factors and exosomes, participating in tumor angiogenesis and tumor metabolism, regulating the immune response in TME and extracellular matrix. However, with the deepening understanding of stromal cells, people found that stromal cells not only have the effect of promoting tumor but also can inhibit tumor in some cases. In this review, we will introduce the origin of stromal cells in TME as well as the role and specific mechanism of stromal cells in tumorigenesis and tumor development and strategies for treatment of tumors based on stromal cells. We will focus on tumor-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated adipocytes (CAAs), tumor endothelial cells (TECs) and pericytes (PCs) in stromal cells.

Albumin-based nanoparticle for dual-modality imaging of the lymphatic system.

The lymphatic system is a complex network of lymphatic vessels, lymph nodes, and lymphoid organs. The current understanding of the basic mechanism and framework of the lymphatic system is relatively limited and not ideal for exploring the function of the lymphatic system, diagnosing lymphatic system diseases, and controlling tumor metastasis. Imaging modalities for evaluating lymphatic system diseases mainly include lymphatic angiography, reactive dye lymphatic angiography, radionuclide lymphatic angiography, computed tomography, and ultrasonography. However, these are insufficient for clinical diagnosis. Some novel imaging methods, such as magnetic resonance imaging, positron emission computed tomography, single-photon emission computed tomography, contrast-enhanced ultrasonography, and near-infrared imaging with agents such as cyanine dyes, can reveal lymphatic system information more accurately and in detail. We fabricated an albumin-based fluorescent probe for dual-modality imaging of the lymphatic system. A near-infrared cyanine dye, IR-780, was absorbed into bovine serum albumin (BSA), which was covalently linked to a molecule of diethylenetriaminepentaacetic acid to chelate gadolinium Gd3+. The fabricated IR-780@BSA@Gd3+ nanocomposite demonstrates strong fluorescence and high near-infrared absorption and can be used as a T1 contrast agent for magnetic resonance imaging. In vivo dual-modality fluorescence and magnetic resonance imaging showed that IR-780@BSA@Gd3+ rapidly returned to the heart through the lymphatic circulation after it was injected into the toe webs of mice, facilitating good lymphatic imaging. The successful fabrication of the new IR-780@BSA@Gd3+ nanocomposite will facilitate the study of the mechanism and morphological structure of the lymphatic system.

Arrangement of Indocyanine Green in a 1.5-Nanometer Channel to Achieve High-Efficiency Imaging of the Intestinal Lymphatic System.

The complications of inflammatory bowel diseases (IBDs) seriously endanger people's health, such as bleeding, polyp hyperplasia, and even cancer. Although the precise pathophysiology of IBD is unknown, alterations in the intestinal lymphatic network, such as lymphangiogenesis and lymphatic vessel dysfunction, are well-established features. Therefore, the development of a reliable technology is urgently required, with a stereoscopic, deep, and high-resolution technology for IBD lymphatic targeting imaging in clinical practice. However, indocyanine green, the only clinically approved imaging agent by the Food and Drug Administration, can easily cause self-aggregation or be interfered with by microenvironments, causing fluorescence quenching, which seriously affects the imaging and detective capabilities. Herein, indocyanine green molecules are arranged in a 1.5-nanometer one-dimensional channel (TpPa-1@ICG). Based on this specified structure, the fluorescence enhancement effect is observed in the TpPa-1@ICG resultant, and the fluorescence intensity is enhanced by 27%. In addition, the ICG-incorporated porous solid reveals outstanding solvent (dichloromethane, tetrahydrofuran, etc.) and thermal (>300 °C) stability. After modifying the target molecules, TpPa-1@ICG showed excellent imaging ability for intestinal lymphatic vessels, providing a new imaging tool for IBDs research.

Ultrabright Renal-Clearable Cyanine-Protein Nanoprobes for High-Quality NIR-II Angiography and Lymphography.

The renal-clearable aspect of imaging agent with minimum toxicity issues and side effects is essential for clinical translation, yet clinical near-infrared-I/II (NIR-I/II) fluorophores with timely renal-clearance pathways are very limited. Herein, we rationally develop the cyanine-protein composite strategy through covalent bonding of ß-lactoglobulin (ß-LG) and chloride-cyanine dye to produce a brilliant and stable NIR-I/II fluorophore (e.g., ß-LG@IR-780). The ß-LG acts as a protecting shell with small molecular weight (18.4 kDa) and ultrasmall size (<5 nm), thus endowing the ß-LG@IR-780 with excellent biocompatibility and renal excretion. Our ß-LG@IR-780 probe enables noninvasive and precise NIR-II visualization of the physiological and pathological conditions of the vascular and lymphatic drainage system, facilitating intraoperative imaging-guided surgery and postoperative noninvasive monitoring. The minimum accumulation of our probes in the main organs improves the overall biosafety. This study provides a facile methodology for new-generation NIR-II fluorophores and largely improves the brightness and pharmacokinetics of small molecular dyes.

Visual analysis of global research output of lymphedema based on bibliometrics.

Background: Globally, several generations of doctors in the field of lymphedema have created numerous publications. To date, no bibliometric analysis has been performed specifically on these publications. For the further promotion of research on lymphedema and to align with the international research frontiers, it is essential to understand the current state of Lymphedema research output. Objective: This study aims to statistically and visually analyze the characteristics of publications output, distribution of contributions and development process of lymphedema, enriching the knowledge base of Lymphedema, and then seek potential research topics and collaborators. Methods: Based on the Web of Science core collection database, we firstly analyzed the quantity and quality of publications in the field of lymphedema, secondly profiled the publishing groups in terms of country, institution, author's publication and cooperation network, and finally sorted out and summarized the hot topics of research. Results: A total of 8569 papers were retrieved from 1900-2021. The top4 journals with the most publications were LYMPHOLOGY, LYMPHATIC RESEARCH AND BIOLOGY, PLASTIC AND RECONSTRUCTIVE SURGERY and ANNALS OF SURGICAL ONCOLOGY. The top 4 countries with the most publications were USA, Japan, UK, and China. The United States dominates the total number of publications and the international cooperation network. The most productive research institution is Harvard University, and the research institution with the most collaborating institutions is Memorial Sloan Kettering Cancer Center. Mortimer, Peter S contributes the most research in this field. The research achievements of Japanese scholars in this field are of great significance. The top 5 ranked keywords are "Breast Cancer", "Health-Related Quality Of Life", "Lymphscintigraphy", "Lymphovenous Anastomosis", and "Lymphangiogenesis". Conclusion: More and more scholars are devoted to the research of cancer-related Lymphedema. It is foreseeable that breast cancer-related lymphedema and lymphangiogenesis will remain a focus of future research. Advances in Lymphatic vessel imaging and the development of lymphatic microsurgery will further play a role in the clinical workup of lymphedema. Meanwhile, This study can help researchers identify potential collaborators and partner institutions and contribute to further research.

A Meta-analysis of 37 Studies on the Effectiveness of Microsurgical Techniques for Lymphedema.

BACKGROUND: Microsurgery is a new technique for lymphedema treatment. Its advantages and disadvantages remain controversial. This study is sought to collect clinical data from patients who underwent lymphovenous bypass and vascularized lymph node transplantation to explore whether surgical procedures can effectively treat lymphedema. METHODS: We performed a meta-analysis of the effectiveness of lymphatic microsurgery. We searched the databases of literature for articles in Chinese and English. These articles were graded for quality. Report details and outcomes were recorded. Data extraction, systematic review, and meta-analysis were performed. RESULTS: Thirty-seven studies were included. Patients who underwent microsurgery had a significantly better chance of achieving an excellent result than patients who received conservative treatment (odds ratio = 7.07). The affected limb circumference was reduced by approximately, 44.68% after the microsurgery. After the microsurgery, 63% of the patients did not need physiotherapy, and 96% were free from painful skin infections. Lymphography showed that lymphatic transport capacity was enhanced. Moreover, 12% of the patients reported that edema reappeared in the long-term, 26% required reoperation for unsatisfactory results, and 32% experienced lymphatic leakage. CONCLUSIONS: A vast majority of patients derive more benefit from lymphatic microsurgery than from conventional treatment. The advantages of lymphatic microsurgery outweigh the disadvantages for patients in the early and middle stages of chronic secondary lymphedema and patients in whom conventional treatment failed.

Preparation of the Biodegradable Lymphatic Targeting Imaging Agent Based on the Indocyanine Green Mesoporous Silicon System.

The lymphatic system plays a crucial role in the immune system's recognition and response to disease. Therefore, the imaging of the lymphatic system, especially lymphatic vessels, has emerged as a valuable tool for the diagnosis of metastasis. FDA-approved small-molecule dyes, namely, indocyanine green (ICG), have been widely applied to lymphatic vessels imaging. However, due to the small physical size, such molecule-based agents show no selectivity, and rapid clearance from lymph nodes. Herein, a biodegradable lymphatic targeting imaging agent based on the ICG-mesoporous silicon system (ICG@HMONs-HA) was obtained, which not only could target lymph vessels but also had a long residence time. The reported work provides a practical way for lymph vessel fluorescence imaging and paves the way for clinical translation of nanomaterial-based tracers.

A Facile and Highly Efficient Approach to Obtain a Fluorescent Chromogenic Porous Organic Polymer for Lymphatic Targeting Imaging.

Porous organic polymers have an open architecture, excellent stability, and tunable structural components, revealing great application potential in the field of fluorescence imaging, but this part of the research is still in its infancy. In this study, we aimed to tailor the physical and chemical characteristics of indocyanine green using sulfonic acid groups and conjugated fragments, and prepared amino-grafted porous polymers. The resulting material had excellent solvent and thermal stability, and possessed a relatively large pore structure with a size of 3.4 nm. Based on the synergistic effect of electrostatic bonding and π-π interactions, the fluorescent chromogenic agent, indocyanine green, was tightly incorporated into the pore cavity of POP solids through a one-step immersion method. Accordingly, the fluorescent chromogenic POP demonstrated excellent imaging capabilities in biological experiments. This preparation of fluorescent chromogenic porous organic polymer illustrates a promising application of POP-based solids in both fluorescence imaging and biomedicine applications.

PSMA-Targeted Supramolecular Nanoparticles Prepared From Cucurbit[8]uril-Based Ternary Host-Guest Recognition for Prostate Cancer Therapy.

Nanomedicines play an important role in cancer therapy; however, some drawbacks including unsatisfactory efficacy and side effects arising from indiscriminate drug release retard their clinical applications. Although functionalization of nanomedicines through covalent interactions can improve the pharmacokinetics and efficacy of the loaded drugs, complicated and tedious synthesis greatly limits the exploration of multifunctional nanoparticles. Herein, we utilize a supramolecular strategy to design a nanomedicine for targeted drug delivery through cucurbit[8]uril-based host-guest ternary complexation and successfully prepare prostate-specific membrane antigen (PSMA)-targeted supramolecular nanoparticles encapsulating doxorubicin (DOX). In vitro studies exhibit targeted modification via noncovalent enhance anticancer efficiency of DOX due to the increased cell uptake on account of receptor-mediated endocytosis. This design provides a new strategy for the development of sophisticated drug delivery systems and holds perspective potentials in precise cancer treatments.

The bright future of nanotechnology in lymphatic system imaging and imaging-guided surgery.

Lymphatic system is identified the second vascular system after the blood circulation in mammalian species, however the research on lymphatic system has long been hampered by the lack of comprehensive imaging modality. Nanomaterials have shown the potential to enhance the quality of lymphatic imaging due to the unparalleled advantages such as the specific passive targeting and efficient co-delivery of cocktail to peripheral lymphatic system, ease molecular engineering for precise active targeting and prolonged retention in the lymphatic system of interest. Multimodal lymphatic imaging based on nanotechnology provides a complementary means to understand the kinetics of lymphoid tissues and quantify its function. In this review, we introduce the established approaches of lymphatic imaging used in clinic and summarize their strengths and weaknesses, and list the critical influence factors on lymphatic imaging. Meanwhile, the recent developments in the field of pre-clinical lymphatic imaging are discussed to shed new lights on the design of new imaging agents, the improvement of delivery methods and imaging-guided surgery strategies.

A novel Near-Infrared fluorescent probe for Zn2+ and CN- double detection based on dicyanoisfluorone derivatives with highly sensitive and selective, and its application in Bioimaging.

We have successfully synthesized NIRF as a near-infrared fluorescence probe for relay recognition of zinc and cyanide ions. The probe possesses well selectivity and anti-interference ability over common ions towards Zn2+ and CN-. The results showed that Zn2+ and the probe formed [NIRF-Zn2+] complex after added Zn2+ into the probe NIRF solution, which emited red fluorescence. The probe can be used for quantitative detection of Zn2+ with a detection limit of 4.61 × 10-8 M. It was determined that the binding stoichiometry between the NIRF and Zn2+ was 1:1 according to the job,s curve. Subsequently, CN- was added to the NIRF-Zn2+ solution, CN- combined with Zn2+ to generate [Zn(CN-)x]1-x due to the stronger binding ability between zinc ion and cyanogen, which lead to the red fluorescence disappeared. The quantitative detection of CN- was realized with a detection limit of 7.9 × 10*7 M. In addition, the probe has excellent specificity and selectivity for Zn2+ and CN-. And the probe can be stable in a wide range of pH. Through biological experiments, we found that it can complete cell imaging in macrophages and imaging of living mice, which has application prospects in Bioimaging. In addition, the probe NIRF has good applicability for Zn2+ and CN- detection in actual samples.

A ROS and shear stress dual-sensitive bionic system with cross-linked dendrimers for atherosclerosis therapy.

Atherosclerosis is an important pathological basis for cardiovascular disease. Thus, the treatment of atherosclerosis can effectively improve the prognosis and reduce the mortality of cardiovascular diseases. In this study, we developed simvastatin acid (SA)-loaded cross-linked dendrimer nanoparticles (SA PAM) that were adsorbed to the surface of red blood cells (RBCs) to obtain SA PAM@RBCs, a ROS and shear stress dual response drug delivery system for the treatment of atherosclerosis. SA PAM could continuously release SA in an H2O2-triggered manner, and effectively eliminate excessive H2O2 in LPS-stimulated RAW 264.7 cells, achieving the target of using the special microenvironment at the plaque to release drugs. At the same time, the shear sensitive model also proved that only 12.4% of SA PAM detached from the RBCs under low shear stress (20 dynes per cm2), while 61.3% SA PAM desorbed from the RBCs under a high shear stress (100 dynes per cm2) stimulus, revealing that SA PAM could desorb in response to the shear stress stimulus. Both the FeCl3 model and ApoE-/- model showed that SA PAM@RBCs had better therapeutic effects than free SA, and with excellent safety in vivo. Therefore, a biomimetic drug delivery system with dual sensitivity to ROS and shear stress would become a promising strategy for the treatment of atherosclerosis.

A novel mitochondrial-targeting fluorescent probe based on 1,4-dihydropyridine to visualize and monitor the viscosity of live cells and mice in vivo.

Cell viscosity is related to some diseases, such as diabetes, atherosclerosis, and Alzheimer's disease. These diseases can cause abnormal viscosity of the cell mitochondrial matrix. 1,4-Dihydropyridine (DHP) is an important organic compound with biological activity and is widely used in drug research. However, there are few studies on its optical properties, especially in the design of viscous fluorescent probes. In this study, a fluorescent probe for viscosity detection using 1,4-dihydropyridine as the fluorophore and indole iodide salt as the recognition group was designed and synthesized. The probe has the advantages of a deep-red emission, low cytotoxicity, good biocompatibility and excellent anti-interference ability. In addition, the probe also has the ability to target mitochondria and has been successfully applied to the detection of the viscosity response of HeLa cells and living mice, and has good clinical application potential.

A novel fluorescent probe based on a triphenylamine derivative for the detection of HSO3- with high sensitivity and selectivity.

A novel highly active fluorescence chemical sensor (TBQN) for HSO3- was synthesized by the Knoevenagel reaction based on triphenylamine-benzothiazole as a new fluorophore. The probe possessed good selectivity toward HSO3- and anti-interference ability with common ions. The fluorescence and UV-vis spectra of the TBQN probe were significantly changed after the addition of HSO3-. At the same time, the probe solution released obvious green fluorescence. Moreover, the limit of detection for HSO3- was calculated to be 3.19 × 10-8 M. The TBQN probe displayed a rapid response to HSO3- and it took about 3 min to complete the recognition. The detection mechanism is the nucleophilic addition reaction between HSO3- and -C[double bond, length as m-dash]C- in the probe molecule. The π-conjugation and ICT (intramolecular charge transfer) transition in the TBQN molecule were destroyed by this addition, which resulted in the change of the fluorescence before and after the addition of HSO3-. Then, the mechanism was verified by theoretical calculations, 1H NMR measurements and mass spectroscopy. In addition, the probe showed low cytotoxicity and could be used for biological imaging in RAW264.7 cells.

Development of a NIR fluorescent probe for highly selective and sensitive detection of cysteine in living cells and in vivo.

Cysteine (Cys) plays important physiological roles in the human body, and abnormal Cys concentrations can cause a variety of diseases. Thus, detecting Cys with high selectivity and sensitivity in vivo is important. Near-infrared (NIR) fluorescent probes are widely employed in biological detection because of their excellent optical properties such as minimal damage to biological samples, low background interference and high signal-to-noise ratio. However, few NIR fluorescent probes that can detect Cys over homocysteine (Hcy) and glutathione (GSH) have been reported because of their similar reactivity and structure. In this work, a highly water-soluble NIR probe (CYNA) for detecting Cys whose structure is similar to that of indocyanine green and is based on cyanine skeleton was synthesized and via aromatic nucleophilic substitution-rearrangement (SNAr-rearrangement) to specific recognize the cysteine. The probe showed high selectivity toward Cys and superior biosecurity, excellent biocompatibility and prolonged dynamic imaging. It also has long fluorescence emission wavelength (820 nm), low detection limit (14 nM) and was successfully applied for visualizing Cys in living cells and mice, which has great promise for applications in noninvasive vivo biological imaging and detection.

A simple nomogram prediction model to identify relatively young patients with mild cognitive impairment who may progress to Alzheimer's disease.

AIM: Construct a clinical predictive model based on easily accessible clinical features and imaging data to identify patients 65 years of age and younger with mild cognitive impairment(MCI) who may progress to Alzheimer's disease(AD). METHODS: From the ADNI database, patients with MCI who were less than or equal to 65 years of age and who had been followed for 6-60 months were selected.We collected demographic data, neuropsychological test scale scores, and structural magnetic images of these patients. Clinical characteristics were then screened, and VBM and SBM analyses were performed using structural nuclear magnetic images to obtain imaging histology characteristics. Finally, predictive models were constructed combining the clinical and imaging histology characteristics. RESULTS: The constructed nomogram has a cross-validated AUC of 0.872 in the training set and 0.867 in the verification set, and the calibration curve fits well.We also provide an online model-based forecasting tool. CONCLUSION: The model has good performance and uses convenience,it should be able to provide assistance in clinical work to screen relatively young MCI patients who may progress to AD.

Shear stress and ROS-responsive biomimetic micelles for atherosclerosis via ROS consumption.

Reactive oxygen species (ROS) are well-known important initiating factors required for atherosclerosis formation, which leads to endothelial dysfunction and plaque formation. Most of the existing antithrombotic therapies use ROS-responsive drug delivery systems, which have a certain therapeutic effect but cannot eliminate excess ROS. Therefore, the atherosclerosis cannot be treated from the source. Moreover, nanoparticles are easily cleared by the immune system during blood circulation, which is not conducive to long-term circulation. In this study, we developed an intelligent response system that could simultaneously respond to ROS and the shear stress microenvironment of atherosclerotic plaques. This system was formed by red blood cells (RBCs) and simvastatin-loaded micelles (SV MC). The micelles consisted of poly(glycidyl methacrylate)-polypropylene sulfide (PGED-PPS). The hydrophobic PPS could react with excess ROS to become hydrophilic, which forced the micelle rupture, resulting in drug release. Most importantly, PPS could also significantly deplete the ROS level, realizing the synergistic treatment of atherosclerosis with drugs and materials. The positively charged SV MC and negatively charged RBCs were self-assembled through electrostatic adsorption to obtain SV MC@RBCs. The SV MC@RBCs could respond to the high shear stress at the atherosclerotic plaque, and the shear stress induced SV MC desorption from the RBC surface. Using biomimetic methods to evade the SV MC@RBCs elimination by the immune system and to reduce the ROS plays a vital role in improving atherosclerosis treatment. The results of in vitro and in vivo experiments showed that SV MC@RBCs could effectively treat atherosclerosis. Moreover, not only does the SV MC@RBCs system avoid the risk of bleeding, but it also has excellent in vivo safety. The study results indicate that the SV MC@RBCs system is a promising therapeutic nanomedicine for treating ROS-related diseases.

Identification of a Transcription Factor Signature That Can Predict Breast Cancer Survival.

BACKGROUND: The expression pattern of transcription factors (TFs) can be used to develop potential prognostic biomarkers for cancer. In this study, we aimed to identify and validate a TF signature for predicting disease-free survival (DFS) of breast cancer (BRCA) patients. METHODS: Lasso and the Cox regression analyses were applied to construct a TF signature based on a gene expression dataset from TCGA. The prognosis value of the TF signature was investigated in the TCGA database, and its reliability was further validated in 3 independent datasets from Gene Expression Omnibus (GEO). The prognosis performance of the TF signature was compared with 4 previously published gene signatures. To investigate the association between the TF signature and hallmarks of cancer, Gene Set Enrichment Analysis (GSEA) was carried out. The correlations of the TF signature and the levels of immune infiltration were also investigated. RESULTS: An 11-TF prognostic signature was constructed with good survival prediction performance for BRCA patients. By using the risk score model based on the 11-TF signature, BRCA patients were stratified into low- and high-risk groups and showed good and poor disease-free survival (DFS), respectively. The risk score was an independent prediction indicator when adjusting for other clinicopathological factors. Furthermore, the 11-TF signature had a better survival prediction performance compared to 4 previously published gene signatures. Moreover, the risk score was a cancer hallmark. Finally, a high-risk score was associated with higher infiltration of M0 and M2 macrophages and was associated with a lower infiltration of resting memory CD4+ T cells and CD8+ T cells. CONCLUSION: The findings in this study identified and validated a novel prognostic TF signature, which is an independent biomarker for the prediction of DFS in BRCA patients.