An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty.

The high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti-stenosis drug-eluting stents face challenges due to their limited functions and long-term safety concerns, significantly compromising their therapeutic effect. Herein, a stent-free anti-stenosis drug coating (denoted as Cur-NO-Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor-peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur-NO-Gel has the capability to release NO upon ß-galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur-NO-Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur-NO-Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.

NIR-II fluorescence and PA imaging guided activation of STING pathway in photothermal therapy for boosting cancer immunotherapy by theranostic thermosensitive liposomes.

Photothermal immunotherapy has shown great potential for efficient cancer treatment. However, the immunosuppressive tumor microenvironment forms a heavy barrier for photothermal-induced anti-tumor immunity by inhibiting dendritic cell (DC) maturation and cytotoxic T cell response. Moreover, the lack of reliable spatiotemporal imaging modalities makes photothermal immunotherapy difficult to guide tumor ablation and monitor therapeutic outcomes in real time. Herein, we designed a theranostic thermosensitive liposome (PLDD) as a versatile nanoplatform to boost the adaptive anti-tumor immunity of photothermal immunotherapy and to achieve multiple bioimaging modalities in a real-time manner. PLDD contains two major functional components: a multifunctional photothermal agent (DTTB) and an immune potentiator STING pathway agonist (DMXAA). Upon irradiation, the heat generated by DTTB induced the immunogenic cell death (ICD) of the tumor and dissociated the structure of thermosensitive liposome to release DMXAA, which ultimately activated the STING pathway and promoted the ICD-induced immune response by increasing DC cell maturation and T cell recruitment. Moreover, the DTTB in PLDD displayed excellent second near-infrared (NIR-II) fluorescence and photoacoustic (PA) dual-modal imaging, which provided omnibearing information on the tumor and guided the subsequent therapeutic operation. Therefore, this versatile PLDD with light-triggered promotion of anti-tumor immunity and multiple spatiotemporal imaging profiles holds great potential for the future development of cancer immunotherapy.

PCSK9 Inhibition: From Current Advances to Evolving Future.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson's disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.

Extracellular vesicles in pancreatic cancer immune escape: Emerging roles and mechanisms.

Pancreatic cancer (PC) is the most lethal malignancy worldwide due to its delayed diagnosis and limited treatment options. Despite great progress in clinical trials of immunotherapies for various cancers, their effectiveness in PC is very low, indicating that immune evasion is still a major obstacle to immunotherapy in PC. However, the mechanism of immune escape in PC is not fully understood, which substantially restricts the development of immunotherapy. As an important component of intercellular communication networks, extracellular vesicles (EVs) have attracted increasing attention in relation to immune escape. This review aims to provide a better understanding of the roles of EVs in tumor immune escape and the potential to expand their application in cancer immunotherapy. The relationship between PC and the tumor immune microenvironment is briefly introduced. Then, the mechanism by which EVs are involved in immune regulation is summarized, and the latest progress in determining the role of EVs in regulating PC immune escape is highlighted.

Engineered extracellular vesicles and their mimetics for cancer immunotherapy.

Extracellular vesicles (EVs) are heterogeneous membranous vesicles secreted by living cells that are involved in many physiological and pathological processes as intermediaries for intercellular communication and molecular transfer. Recent studies have shown that EVs can regulate the occurrence and development of tumors by transferring proteins, lipids and nucleic acids to immune cells as signaling molecules. As a new diagnostic biomarker and drug delivery system, EVs have broad application prospects in immunotherapy. In addition, the breakthrough of nanotechnology has promoted the development and exploration of engineered EVs for immune-targeted therapy. Herein, we review the uniqueness of EVs in immune regulation and the engineering strategies used for immunotherapy and highlight the logic of their design through typical examples. The present situation and challenges of clinical transformation are discussed, and the development prospects of EVs in immunotherapy are proposed. The goal of this review is to provide new insights into the design of immune-regulatory EVs and expand their application in cancer immunotherapy.

Homogeneous Polyporus Polysaccharide Inhibit Bladder Cancer by Resetting Tumor-Associated Macrophages Toward M1 Through NF-κB/NLRP3 Signaling.

Bladder cancer(BC)is one of the most common urinary system tumors, which characterized by a high incidence. Polyporus polysaccharide is the main active component of polyporus, which is clinically used in the treatment of bladder cancer, but the mechanism is not clear. In previous study, we isolated homogeneous polyporus polysaccharide(HPP) with high purity from polyporus. The goal of this study was to assess the polarization of macrophages induced by HPP in the bladder tumor microenvironment and explored its anti-bladder cancer mechanism through BBN bladder cancer rat model and Tumor associated macrophages(TAM). The results suggested that HPP regulates TAM polarization to improve the tumor inflammatory microenvironment, possibly through the NF-κB/NLRP3 signaling pathway. Our results suggested that HPP may be a potential therapeutic agent for bladder tumors.

Designer Functional Nanomedicine for Myocardial Repair by Regulating the Inflammatory Microenvironment.

Acute myocardial infarction is a major global health problem, and the repair of damaged myocardium is still a major challenge. Myocardial injury triggers an inflammatory response: immune cells infiltrate into the myocardium while activating myofibroblasts and vascular endothelial cells, promoting tissue repair and scar formation. Fragments released by cardiomyocytes become endogenous "danger signals", which are recognized by cardiac pattern recognition receptors, activate resident cardiac immune cells, release thrombin factors and inflammatory mediators, and trigger severe inflammatory responses. Inflammatory signaling plays an important role in the dilation and fibrosis remodeling of the infarcted heart, and is a key event driving the pathogenesis of post-infarct heart failure. At present, there is no effective way to reverse the inflammatory microenvironment in injured myocardium, so it is urgent to find new therapeutic and diagnostic strategies. Nanomedicine, the application of nanoparticles for the prevention, treatment, and imaging of disease, has produced a number of promising applications. This review discusses the treatment and challenges of myocardial injury and describes the advantages of functional nanoparticles in regulating the myocardial inflammatory microenvironment and overcoming side effects. In addition, the role of inflammatory signals in regulating the repair and remodeling of infarcted hearts is discussed, and specific therapeutic targets are identified to provide new therapeutic ideas for the treatment of myocardial injury.

Therapeutic Applications of Extracellular Vesicles for Myocardial Repair.

Cardiovascular disease is the leading cause of human death worldwide. Drug thrombolysis, percutaneous coronary intervention, coronary artery bypass grafting and other methods are used to restore blood perfusion for coronary artery stenosis and blockage. The treatments listed prolong lifespan, however, rate of mortality ultimately remains the same. This is due to the irreversible damage sustained by myocardium, in which millions of heart cells are lost during myocardial infarction. The lack of pragmatic methods of myocardial restoration remains the greatest challenge for effective treatment. Exosomes are small extracellular vesicles (EVs) actively secreted by all cell types that act as effective transmitters of biological signals which contribute to both reparative and pathological processes within the heart. Exosomes have become the focus of many researchers as a novel drug delivery system due to the advantages of low toxicity, little immunogenicity and good permeability. In this review, we discuss the progress and challenges of EVs in myocardial repair, and review the recent development of extracellular vesicle-loading systems based on their unique nanostructures and physiological functions, as well as the application of engineering modifications in the diagnosis and treatment of myocardial repair.

Danlou Tablets Inhibit Atherosclerosis in Apolipoprotein E-Deficient Mice by Inducing Macrophage Autophagy: The Role of the PI3K-Akt-mTOR Pathway.

Atherosclerosis (AS) is a type of chronic vascular disease, and its etiology is not yet fully understood. AS is characterized by lipid deposition, atherosclerotic plaque formation, vascular stenosis or even complete blockage of the blood vessel wall. Clinical studies have shown that Danlou tablets (DLTs) can improve the heart function, quality of life, and prognosis of patients with coronary heart disease and myocardial infarction. However, its mechanism of action remains unknown. Our study revealed that DLTs ameliorated ApoE-/-AS mouse aortic atherosclerotic plaques [hematoxylin-eosin (HE) staining and small animal ultrasound] and reduced CD68+ macrophage infiltration, the expression of the inflammatory factor interferon-gamma (IFN-γ), vascular smooth muscle α-actin, and serum lipid levels. In vitro, in the macrophage foaming model, DLTs partially restored the activity of RAW264.7 cells, reduced the uptake of lipid droplets, and inhibited lipid droplet accumulation and apoptosis within BMDMs. We also found that Torin1, an autophagy agonist, reduced intracellular lipid deposition in BMDMs, as did DLTs. Moreover, DLTs upregulated the expression of the autophagy-related protein LC3II and decreased p62 accumulation in RAW264.7 cells. DLTs also inhibited the phosphorylation of p-PI3K, p-Akt, and p-mTOR, leading to upregulated autophagy in RAW264.7 cells. In summary, our results suggested that DLTs can promote autophagy in macrophages by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing foam cell formation and improving atherosclerosis.

Therapeutic Applications of Functional Nanomaterials for Prostatitis.

Prostatitis is a common disease in adult males, with characteristics of a poor treatment response and easy recurrence, which seriously affects the patient's quality of life. The prostate is located deep in the pelvic cavity, and thus a traditional infusion or other treatment methods are unable to easily act directly on the prostate, leading to poor therapeutic effects. Therefore, the development of new diagnostic and treatment strategies has become a research hotspot in the field of prostatitis treatment. In recent years, nanomaterials have been widely used in the diagnosis and treatment of various infectious diseases. Nanotechnology is a promising tool for 1) the accurate diagnosis of diseases; 2) improving the targeting of drug delivery systems; 3) intelligent, controlled drug release; and 4) multimode collaborative treatment, which is expected to be applied in the diagnosis and treatment of prostatitis. Nanotechnology is attracting attention in the diagnosis, prevention and treatment of prostatitis. However, as a new research area, systematic reviews on the application of nanomaterials in the diagnosis and treatment of prostatitis are still lacking. In this mini-review, we will highlight the treatment approaches for and challenges associated with prostatitis and describe the advantages of functional nanoparticles in improving treatment effectiveness and overcoming side effects.

FDTD Simulation: Simultaneous Measurement of the Refractive Index and the Pressure Using Microdisk Resonator with Two Whispering-Gallery Modes.

In this paper, an approach to measure both the refractive index (RI) and the pressure simultaneously using two Whispering-Gallery Modes (WGMs) in a microdisk resonator is theoretically proposed. Due to the difference in the energy distribution of the first and second order WGMs, the sensitivity of two modes toward the variation of RI and pressure applied to the device show differences. An RI sensitivity of 29.07 nm/RIU and pressure sensitivity of 0.576 pm/kPa for WGM (1,36), and an RI sensitivity of 38.68 nm/RIU and a pressure sensitivity of 0.589 pm/kPa for WGM (2,28) are obtained through the 3D finite-difference time-domain (3D-FDTD) simulation. Dual parametric sensing can be achieved by solving the second-order inverse sensitivity matrix. Therefore, strain-optical coupling behavior is effectively eliminated. The dual sensing scheme we proposed provides a novel approach to overcome the difficulty of multi-sensing applications based on the flexible photonic device.

The mitochondrial genome of Argyra pingwuensis (Diptera: Dolichopodidae).

The long-legged fly Argyra pingwuenesis Qilemoge, Wang et Yang (Genbank accession number: MK905737) belongs to the subfamily Diaphorinae of Dolichopodidae. The mitogenome of A. pingwuenesis was sequenced, the first representative of the mitogenome of the subfamily. The mitogenome is 15,859 bp long, consisting of 13 protein-coding genes, 2 rRNAs, and 22 transfer RNAs. All genes have the similar locations and strands with that of other published species of Dolichopodidae. The nucleotide composition biases toward A and T, which together made up 74.6% of the entirety. Bayesian inference analysis strongly supported the monophyly of Dolichopodidae. It suggested that subfamily Diaphorinae is the sister group of subfamily Rhaphiinae.

The mitochondrial genome of Suillia sp. (Diptera: Heleomyzidae).

The mitogenome of Suillia sp. was sequenced as the first representative of the family Heleomyzidae. The mitogenome is 15,660 bp totally, consisting of 13 protein-coding genes, 2 rRNAs, and 22 transfer RNAs. The nucleotide composition biases toward A and T is 75.1％ of the entirety. All PCGs start with ATN codons except COI and ND1 and end with TAA or incomplete stop codon. Phylogenetic analyses based on 9 dipteran species supported the relationship of Opomyzoidea + (Ephydroidea + (Lauxanioidea + (Sciomyzoidea + (Sphaeroceroidea + Tephritoidea)))).