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"Lu, Yongxiang"
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Nobiletin protects against myocardial injury and myocardial apoptosis following coronary microembolization via activating PI3K/Akt pathway in rats
It has been found that use of drugs which upregulate the PI3K/Akt pathway can effectively reduce cardiomyocyte apoptosis which has been induced by coronary microembolization (CME). However, whether this functional protein is able to be modified through pretreatment via nobiletin (NOB) in models of CME has not yet been investigated. Therefore, this study set out to explore the cardioprotective effect of NOB on rats with myocardial injuries induced by CME and also explored the potential mechanism which underlies this cardioprotective effect. The study used 40 Sprague-Dawley (SD) rats, which were randomized into four groups: the sham, CME, CME+NOB, and CME+NOB+LY294002 (LY) groups. Twelve hours after surgery, levels of microinfarct, serum c-troponin I (cTnI), cardiac function, apoptotic index, and oxidative stress [superoxide dismutase (SOD) and malondialdehyde (MDA)] were measured for rats in each group. Western blot analysis was performed to detect any protein involved in the PI3K/Akt pathway. Nobiletin improved cardiac dysfunction which had been induced by CME, decreased serum level of cTnI and MDA, and increased serum SOD activities. In addition, nobiletin inhibited myocardial apoptosis, which may be connected to downregulated apoptotic index, upregulated Bcl-2, and cleaved caspase-3 and Bax, while it increased protein levels in phosphorylated Akt. However, when nobiletin was co-administered with LY294002, a PI3K (phosphatidylinositol 3-kinase)/Akt inhibitor, all of the previously mentioned effects were blocked. Nobiletin is able to inhibit cardiomyocyte apoptosis and can consequently attenuate CME-induced myocardial injuries. These functions are realized through the activation of the PI3K/Akt signaling pathway as well as by reducing oxidative stress.
Journal Article
Synergistic Mechanisms and Operational Parameter Optimization of Excavation–Muck Removal Systems in AGF Shaft Sinking
Shaft sinking in soft, water-rich strata frequently suffers from low cutting efficiency, cycle-time mismatches between excavation and muck removal, and weak system-level coordination. To elucidate the synergistic mechanisms governing excavation–muck removal interactions and to realize end-to-end performance gains, we investigate the East Ventilation Shaft of the Xinjie Taigemiao mining district as a representative artificial ground freezing (AGF) project. First, drawing on the mechanics of frozen ground and field monitoring, we establish a relationship model linking advance rate, drum rotational speed, cutting depth, and muck production, thereby clarifying why lower rotational speeds, moderate cutting depths, and rational traction reduce energy consumption and mitigate disturbances to the frozen wall. Next, for muck handling, we build a full-process discrete element method (DEM) model, integrate design-of-experiments with response-surface optimization to identify key factors, calibrate contact models, and select collection geometries. The results show that a graded-angle collecting structure improves pile concentration and discharge compliance; combined with a tiered chain-bucket–vertical belt–twin-skip configuration, it delivers matched cycle times and stable “gather–convey–hoist” operation. Finally, two-stage full-scale tests jointly validate excavation and muck removal, demonstrating that the proposed synergy model and optimized parameters sustain continuous, efficient performance across operating conditions. The study provides a reusable mechanistic framework and parameterization blueprint for AGF shaft design and construction.
Journal Article
Empagliflozin Preserves Cardiomyocyte Structural Homeostasis via the Stabilization of the Integrin α5–Desmocollin-2 Adhesion Axis in Sepsis-Induced Cardiomyopathy
Sepsis-induced cardiomyopathy is a life-threatening complication lacking targeted therapies. While empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, confers robust cardioprotection, its specific efficacy in treating sepsis-induced cardiomyopathy and the Empa mechanisms remain poorly defined, limiting its targeted therapeutic use. In this study, we investigated Empa’s effects and its novel mechanisms in a murine lipopolysaccharide (LPS)-induced model of septic cardiomyopathy. Empa pre-treatment effectively prevented LPS-induced cardiac dysfunction, preserving ejection fraction and mitigating myocardial injury (assessed by histology and ELISA) and fibrosis. Transcriptomic analysis revealed that Empa’s protective effects were profoundly linked to the preservation of cardiomyocyte cytoskeletal pathways, alongside its anti-inflammatory actions. The results indicate that LPS induced a pathological dissociation of the matrix protein Integrin α5 (ITGA5) from the cell–cell adhesion protein Desmocollin-2 (DSC2), a structural disruption completely abrogated by Empa in vivo. This ITGA5-DSC2 stabilization was further confirmed to be a cardiomyocyte-intrinsic effect, recapitulated in vitro in both neonatal mouse cardiomyocytes and human AC16 cells. Building on this mechanistic insight, a computational design was successfully employed to develop 13 novel helical protein binders specifically targeting the ITGA5, yielding candidates with favorable structural properties as potential therapeutic leads. These findings establish the cardiomyocyte structural homeostasis via the ITGA5-DSC2 adhesion axis as a novel, key SGLT2-independent mechanism for empagliflozin’s cardioprotection, revealing promising new therapeutic approaches for sepsis-induced cardiomyopathy.
Journal Article
Identification of Protein Markers for Chronic Ischemic Heart Disease Through Integrated Analysis of the Human Plasma Proteome and Genome-Wide Association Data
Background: Chronic ischemic heart disease (CIHD) is characterized by persistent myocardial ischemic due to long-term reduced coronary blood flow. In the past, we mainly relied on surgical intervention or drug therapy to alleviate symptoms, but effective targeted treatments were scarce. Proteomics serves as a key tool to identify novel therapeutic targets. Methods: This study performed a bidirectional Mendelian randomization (MR) analysis by integrating genome-wide association study (GWAS) data on CIHD (10,894,596 single-nucleotide polymorphisms) with plasma proteomic data encompassing 4907 proteins. We conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify pathways linked to candidate protein biomarkers, searched the National Genomics Data Center (NGDC) database for existing evidence of their association with CIHD, and evaluated druggability through multi-dimensional analysis integrating the DSIGDB, ChEMBL, and clinical trial databases. Results: After eliminating the reverse effect, ultimately identifying 28 protein markers, including 16 risk-associated and 12 protective proteins. We also investigated their roles in the pathways related to CIHD. Meanwhile, the search confirmed that five of them were newly discovered protein markers. Ultimately, through evaluation, three priority therapeutic targets (CXCL12, PLAU, CD14) were identified for development. Conclusions: This study identified some biomarkers related to CIHD and analyzed the possible pathways involved. It also provided some new insights into the identification of the target and druggability.
Journal Article
Progranulin’s Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease
Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality globally, prompting the investigation of novel therapeutic targets. Progranulin (PGRN), a glycoprotein initially associated with neurodegenerative disorders, has emerged as a critical protective agent in cardiovascular health. Recent studies indicate that PGRN exerts its protective effects through various mechanisms, including the modulation of inflammatory pathways, enhancement of mitochondrial function, and promotion of vascular integrity. By engaging with key signaling pathways, such as PI3K/Akt, NF-κB and Wnt/β-catenin, PGRN mitigates oxidative stress and fosters an environment conducive to cardiac repair following ischemic injury. Furthermore, PGRN’s role in lipid metabolism and vascular smooth muscle cell behavior highlights its complexity in influencing atherogenesis and vascular homeostasis. This review synthesizes current knowledge regarding PGRN’s protective mechanisms in CVD, emphasizing its potential as a therapeutic target and paving the way for innovative approaches to prevent and treat cardiovascular diseases, ultimately improving patient outcomes in this critical area of public health.
Journal Article
Effect of phenyllactic acid on silage fermentation and bacterial community of reed canary grass on the Qinghai Tibetan Plateau
Background
This study aimed to investigate the effect of phenyllactic acid as an additive on silage fermentation and bacterial community of reed canary grass (RCG,
Phalaris arundinacea
L.) on the Qinghai Tibetan Plateau. At the heading stage, RCG was harvested, chopped and ensiled in small bag silos. The silage was treated without (control, 1.0 g/mL sterile water, on a fresh matter basis (FM)) or with phenyllactic acid (PLA, 3 mg/mL, FM), antimicrobial additive (PSB, a mixture of potassium sorbate and sodium benzoate, 2%, FM), lactic acid bacteria inoculant (LABi,
L. plantarum
+
L. curvatus
, 1 × 10
6
cfu/g, FM) and PLA + LABi, and then stored in a dark room at the ambient temperature (5 ~ 15 °C) for 60 days.
Results
Compared with control, PLA decreased lactic acid, acetic acid and ammonia-N contents, and subsequently increased CP content of RCG silage. PLA enhanced the growth of lactic acid bacteria and reduced the count of yeasts (
P
< 0.05) in RCG silage, with reduced bacterial richness index (Chao1), observed operational taxonomic units and diversity index (Simpson). In relative to control, moreover, PLA and PLA + LABi increased the relative abundance of
Lactococcus
in RCG silage by 27.73 and 16.93%, respectively.
Conclusions
Therefore, phenyllactic acid at ensiling improved nutritional quality of RCG silage by advancing the disappearance of yeasts and the dominance of
Lactococcus
.
Journal Article
A review of passive self-sensing tag
Purpose
Radio frequency identification tags for passive sensing have attracted wide attention in the area of Internet of Things (IoT). Among them, some tags can sense the property change of objects without an integrated sensor, which is a new trend of passive sensing based on tag. The purpose of this paper is to review recent research on passive self-sensing tags (PSSTs).
Design/methodology/approach
The PSSTs reported in the past decade are classified in terms of sensing mode, composition and the ways of power supply. This paper presents operation principles of PSSTs and analyzes the characteristics of them. Moreover, the paper focuses on summarizing the latest sensing parameters of PSSTs and their matching equipment. Finally, some potential applications and challenges faced by this emerging technique are discussed.
Findings
PSST is suitable for long-term and large-scale monitoring compared to conventional sensors because it gets rid of the limitation of battery and has relatively low cost. Also, the static information of objects stored in different PSSTs can be identified by a single reader without touch.
Originality/value
This paper provides a detailed and timely review of the rapidly growing research in PSST.
Journal Article