Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin.

The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.

Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy.

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.

Complex genetic architecture underlying the plasticity of maize agronomic traits.

Phenotypic plasticity is the ability of a given genotype to produce multiple phenotypes in response to changing environmental conditions. Understanding the genetic basis of phenotypic plasticity and establishing a predictive model is highly relevant to future agriculture under a changing climate. Here we report findings on the genetic basis of phenotypic plasticity for 23 complex traits using a diverse maize population planted at five sites with distinct environmental conditions. We found that latitude-related environmental factors were the main drivers of across-site variation in flowering time traits but not in plant architecture or yield traits. For the 23 traits, we detected 109 quantitative trait loci (QTLs), 29 for mean values, 66 for plasticity, and 14 for both parameters, and 80% of the QTLs interacted with latitude. The effects of several QTLs changed in magnitude or sign, driving variation in phenotypic plasticity. We experimentally validated one plastic gene, ZmTPS14.1, whose effect was likely mediated by the compensation effect of ZmSPL6 from a downstream pathway. By integrating genetic diversity, environmental variation, and their interaction into a joint model, we could provide site-specific predictions with increased accuracy by as much as 9.9%, 2.2%, and 2.6% for days to tassel, plant height, and ear weight, respectively. This study revealed a complex genetic architecture involving multiple alleles, pleiotropy, and genotype-by-environment interaction that underlies variation in the mean and plasticity of maize complex traits. It provides novel insights into the dynamic genetic architecture of agronomic traits in response to changing environments, paving a practical way toward precision agriculture.

Acute coronary syndrome with severe atherosclerotic and hyperthyroidism: A case report.

BACKGROUND: Acute coronary syndrome (ACS) encompasses a spectrum of cardiovascular emergencies arising from the obstruction of coronary artery blood flow and acute myocardial ischemia. Recent studies have revealed that thyroid function is closely related to ACS. However, only a few reports of thyrotoxicosis-induced ACS with severe atherosclerosis have been reported. CASE SUMMARY: A 33-year-old man, who had a history of hyperthyroidism without taking any antithyroid drugs and no history of coronary heart disease, experienced neck pain with occasional heart palpitations starting 3 mo prior that were aggravated after an activity. As the symptoms worsened at 21 d prior, he went to a hospital for treatment. The electrocardiogram examination showed a multilead ST segment elevation and pathological Q waves. Based on these findings and his symptoms, the patient was diagnosed with a suspected myocardial infarction and transferred to our hospital on July 2, 2020. He was diagnosed with a rare case of ACS due to coronary artery atherosclerosis in the anterior descending artery complicated by hyperthyroidism. A paclitaxel-coated drug balloon was used for treatment to avoid the use of metal stents, thus reducing the time of antiplatelet therapy and facilitating the continued treatment of hyperthyroidism. The 9-mo follow-up showed favorable results. CONCLUSION: This case highlights that atherosclerosis is a cause of ACS that cannot be ignored even in a patient with hyperthyroidism.

TTR Gly83Arg Mutation: Beyond Familial Vitreous Amyloidosis.

BACKGROUND: Gly83Arg variation is a type of TTR mutation specific to the Chinese population. Patients of hereditary transthyretin amyloidosis (ATTR) with Gly83Arg variation predominantly present with blurred vision and most of these cases are reported by ophthalmologists. There is currently no systematic assessment of extraocular features of ATTR with Gly83Arg variation. METHODS: Six patients and two asymptomatic carriers with molecularly confirmed Gly83Arg variation of ATTR from three unrelated families were identified by sequencing the TTR gene. The clinical, electrophysiological, ultrasonic, and pathological data were collected and analyzed. RESULTS: This study included six patients and two carriers with TTR Gly83Arg mutation, all of whom came from the Han nationality of China. The average age of onset for the six patients was 39 years, and the course of disease ranged from 5 to 19 years. All the patients started with blurred vision, which was diagnosed as vitreous opacity (VO). Most of the patients developed sensory-motor polyneuropathies over years or even more than a decade (4-15 years) after VO. However, the heterogeneity of peripheral neuropathies among these patients remained large between families. Autonomic impairment also occurred after VO, with varying degrees of abnormalities seen in the associated autonomic assessments. None of the patients had any symptoms of cardiac impairment, but abnormal results were found in examinations. A combined biopsy of the sural nerve and muscle was also performed. Nerve pathology revealed the moderately reduced myelinated nerve fiber density and muscle pathology showed predominant neurogenic impairment accompanied by possible myogenic impairment. CONCLUSIONS: This is a detailed account of Gly83Arg mutation-related ATTR, focusing on the extraocular presentations of this special variant in Chinese. Clinical features of this variant are early-onset, ocular involvement predominance, neurological, and cardiac involvement along with the disease, and relatively long survival.

High-Throughput CRISPR/Cas9 Mutagenesis Streamlines Trait Gene Identification in Maize.

Maize (Zea mays) is one of the most important crops in the world. However, few agronomically important maize genes have been cloned and used for trait improvement, due to its complex genome and genetic architecture. Here, we integrated multiplexed CRISPR/Cas9-based high-throughput targeted mutagenesis with genetic mapping and genomic approaches to successfully target 743 candidate genes corresponding to traits relevant for agronomy and nutrition. After low-cost barcode-based deep sequencing, 412 edited sequences covering 118 genes were precisely identified from individuals showing clear phenotypic changes. The profiles of the associated gene-editing events were similar to those identified in human cell lines and consequently are predictable using an existing algorithm originally designed for human studies. We observed unexpected but frequent homology-directed repair through endogenous templates that was likely caused by spatial contact between distinct chromosomes. Based on the characterization and interpretation of gene function from several examples, we demonstrate that the integration of forward and reverse genetics via a targeted mutagenesis library promises rapid validation of important agronomic genes for crops with complex genomes. Beyond specific findings, this study also guides further optimization of high-throughput CRISPR experiments in plants.