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Breast cancer (BC) has become a severe threat to women, which has imposed excessive pressure on society. LncRNAs play a crucial role in the occurrence and development of BC. This study aimed to evaluate the lncRNA SIAH2 antisense RNA 1 (SIAH2-AS1) role in the development and progression of BC and explore the mechanism of SIAH2-AS1 related Wnt signaling pathway in BC. Malignant and paracancer normal breast tissue samples were obtained from patients who underwent surgery at the Second Affiliated Hospital of Zunyi Medical University. Subsequently, quantitative RT-PCR (qRT-PCR) was performed with these acquired tissue samples to evaluate the concentrations of SIAH2-AS1. Furthermore, CCK-8 assays, colony formation, wound healing, and transwell were performed to investigate the cell proliferation, migration, and invasion respectively. Western blotting was eventually performed for the investigation of proteins and EMT-related markers in the Wnt/β-catenin signaling pathway. The expression of SIAH2-AS1 was up-regulated in cancer tissues and cells. Cell proliferation, colony formation, invasiveness, and migration are significantly reduced by silencing SIAH2-AS1. Moreover, E-cadherin expression in BC cells was increased, whereas N-cadherin and vimentin expression was decreased, when SIAH2-AS1 was eliminated from the cells. Additionally, the Wnt/β-catenin signaling pathways cyclin D1 and C-myc proteins were also significantly downregulated in BC cells when SIAH2-AS1 was knocked out. Our study confirms that SIAH2-AS1 activates the Wnt/β-catenin pathway and has an oncogenic activity that promotes the prognosis of BC, suggesting that SIAH2-AS1 may be a potential drug target for BC. The development of small - molecule inhibitors capable of specifically targeting SIAH2 - AS1 to target and modify the SIAH2 - AS1 gene in cancer cells may offer a novel strategy for clinical treatment. Keywords: breast cancer; cell proliferation; cell migration; Long noncoding RNA; Wnt signaling pathway

Vascular calcification (VC), pathologically characterized by ectopic calcium-phosphate deposition, demonstrates a significant correlation with cardio-cerebrovascular morbidity and adverse clinical outcomes. Despite its clinical relevance, current interventions to prevent and treat VC progression remain limited in efficacy. Numerous studies have demonstrated that Repulsive Guidance Molecule A (RGMa) plays a pivotal role in cardio-cerebrovascular diseases. This investigation aimed to elucidate the role of RGMa in VC and to explore the underlying molecular mechanisms. This study systematically investigated the dynamic alterations in RGMa expression during VC progression through integrated in vitro and in vivo experimental models. The functional regulatory role of RGMa in VC pathogenesis and its molecular mechanistic basis were further elucidated via lentiviral short hairpin RNA (shRNA)-mediated RGMa knockdown and adeno-associated virus serotype 9 (AAV9)-delivered gene silencing, combined with pharmacological inhibition of AKT signaling using the selective inhibitor MK-2206. Alizarin Red S staining and calcium content assays demonstrated that VC and vascular smooth muscle cell (VSMC) calcification were successfully induced in vivo (via subcutaneous vitamin D3 overdose) and in vitro (through high-phosphate medium culture), respectively. Western blot (WB) and immunofluorescence (IF) analyses revealed a significant upregulation of RGMa expression in calcified VSMCs. We successfully constructed a VSMC-specific RGMa-targeting AAV, and RGMa knockdown effectively attenuated VC. These findings indicate that RGMa plays a pivotal role in VSMC calcification. Finally, we investigated whether RGMa exerts its effects via the AKT pathway. In the in vitro model, treatment with the AKT inhibitor MK-2206 suppressed osteogenic marker expression in high phosphate-treated VSMCs without reversing RGMa upregulation. This study indicates that RGMa may promote VC by modulating AKT activation, highlighting RGMa as a promising new molecular target for the treatment of VC.

The aroma, taste, and flavour profiles of mango cultivars vary, directly influencing their marketability and consumer acceptance. In this study, we explored the effects of volatile organic compounds (VOCs) on the distinct aromas of two mango cultivars during storage using GC-IMS and HS-SPME-GC-MS combined with OPLS-DA analysis. Our findings revealed that the terpene and aldehyde contents were higher in the ‘Tainong’ mango cultivar, compared to the ‘Hongyu’ mango, while the ester content was lower. The aroma was attributed to the presence of terpinolene, 2-nonenal, delta-carene, and alpha-phellandrene in the early stages of storage, and later—between 5 and 11 days—to ethyl acetate, ethyl butyrate, and ethyl propanoate. Further analysis of characteristic VOCs using OPLS-DA demonstrated and explained the strong grassy aroma of the ‘Tainong’ mango, and the strong fruity and sweet aromas of the ‘Hongyu’ mango. Additionally, esters mainly accumulated during the later periods of storage, especially propyl butyrate, which was produced and accumulated when fruit quality deteriorated in the later storage period. Our study provides a theoretical basis for detecting mango VOCs during storage to determine the appropriate marketing time for the two mango cultivars and enables informed consumer choice.

With the rapid development of advanced technologies in the Internet of Things era, higher requirements are needed for next‐generation electronic devices. Fortunately, organic thin film transistors (OTFTs) provide an effective solution for electronic skin and flexible wearable devices due to their intrinsic features of mechanical flexibility, lightweight, simple fabrication process, and good biocompatibility. So far considerable efforts have been devoted to this research field. This article reviews recent advances in various promising and state‐of‐the‐art OTFTs as well as related integrated circuits with the main focuses on: (I) material categories of high‐mobility organic semiconductors for both individual transistors and integrated circuits; (II) effective device architectures and processing techniques for large‐area fabrication; (III) important performance metrics of organic integrated circuits and realization of digital and analog devices for future smart life; (IV) applicable analytical models and design flow to accelerate the circuit design. In addition, the emerging challenges of OTFT‐based integrated circuits, such as transistor uniformity and stability are also discussed, and the possible methods to solve these problems at both transistor and circuit levels are summarized. Organic thin film transistors (OTFTs) hold great potential for future smart life due to their intrinsic features of mechanical flexibility, lightweight, simple fabrication process, and good biocompatibility. This article reviews recent advances in various promising and state‐of‐the‐art OTFTs as well as related integrated circuits with the main focus on high‐performance material categories, device architectures and processing techniques, digital and analog devices, and analytical models and design flow. Additionally, the emerging challenges of OTFT‐based integrated circuits and possible solutions are also discussed.

Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments. Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue. Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis—multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2. Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.

Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmacological interventions. In this study, we conducted an integrative drug repurposing analysis utilizing three distinct approaches. Firstly, we analyzed skeletal muscle transcriptomic sequencing data in humans and mice using gene differential expression analysis, weighted gene co-expression analysis, and gene set enrichment analysis. Subsequently, we employed gene expression profile similarity assessment, hub gene expression reversal, and disease-related pathway enrichment to identify and repurpose candidate drugs, followed by the integration of findings with rank aggregation algorithms. Vorinostat, the top-ranking drug, was also validated in an in vitro study, which demonstrated its efficacy in promoting muscle fiber formation. Although still requiring further validation in animal models and human clinical trials, these results suggest a promising drug repurposing prospect in the treatment and prevention of sarcopenia.

Sunite sheep are well-adapted to the cold Mongolian steppe, exhibiting robust metabolic flexibility in which adipose tissue contributes significantly to energy homeostasis. Proteomics analysis of scapular fat in Sunite sheep during winter and summer identified 432 upregulated and 493 downregulated differentially expressed proteins (DEPs). These DEPs were notably enriched in essential biological functions such as energy metabolism, lipogenesis, and thermogenesis. Furthermore, they exhibited significant enrichment of signaling pathways such as oxidative phosphorylation and fatty acid metabolism. Meanwhile, the precursor protein of asprosin (ASP),profibrillin-1 (pFBN1), showed a marked decrease during winter. Given that ASP had been demonstrated to exert metabolic regulatory effects promoting lipid synthesis and suppressing thermogenesis in model animals, it was hypothesized that the seasonal downregulation of pFBN1 might drive adaptive thermogenesis through ASP. Therefore, this study focused on functional validation of the ASP-encoding gene FBN1 (fibrillin-1). In Adipose-Derived Mesenchymal Stem Cells (ADMSCs), FBN1 was specifically downregulated through overexpressing of its regulatory factor miR-29b-1. The results indicated that downregulation of the FBN1 led to the inhibition of adipogenesis in ADMSCs. This was reflected by a reduction in the number of lipid droplets, a decrease in the expression of adipogenesis marker genes, and a significant drop in triglyceride levels. Furthermore, the reduction in FBN1 levels enhanced the thermogenic function of differentiated adipocytes derived from ADMSCs, as evidenced by enhanced expression of thermogenic marker genes, along with a notable rise in both uncoupling protein 1 (UCP1) and non-esterified fatty acid (NEFA) levels.

Ischemic stroke is a leading cause of death and disability worldwide, and the main goals of stroke treatment are to destroy the thrombus to recanalize blood vessels and protect tissue from ischemia/reperfusion injury. However, current recanalization therapies have serious limitations and there are few neuroprotection methods. Hence, an artificial nanoplatform loaded with anti‐Repulsive Guidance Molecule a monoclonal antibody (anti‐RGMa) and coated with microglia membrane (MiCM) is reported for stroke treatment, namely MiCM@PLGA/anti‐RGMa/Fe3O4@PFH (MiCM‐NPs). Tail vein injection of MiCM‐NPs targeted the ischemia‐damaged endothelial cells because of the MiCM, then superparamagnetic iron oxide (Fe3O4) and anti‐RGMa are released after external low‐intensity focused ultrasound (LIFU) exposure. The thrombus is destroyed by LIFU‐induced “liquid‐to‐gas” phase transition and cavitation of perfluorohexane (PFH) as well as Fe3O4 movements induced by an external magnetic field. Anti‐RGMa protected the ischemic region from ischemia/reperfusion injury. The nanoplatform enabled visualization of the thrombus by ultrasound/photoacoustic imaging when the clot is in an extracranial artery. Importantly, in vivo animal studies revealed good safety for MiCM‐NPs treatment. In conclusion, this nanoplatform shows promise as an ischemic stroke treatment strategy combining targeted delivery, recanalization, and neuroprotection. This research reports an artificial nanoplatform namely MiCM@PLGA/anti‐RGMa/Fe3O4@PFH: PFH as a core, loaded with anti‐RGMa and Fe3O4, coated with microglia membrane (MiCM) for stroke treatment. The nanoplatform targets the ischemia‐damaged endothelial cells of thrombus site because of MiCM, and Fe3O4 and anti‐RGMa are released after LIFU exposure. The thrombus is destroyed by PFH and Fe3O4. Anti‐RGMa protects the ischemic region.

Structural defects in the zona pellucida (ZP), caused by mutations in ZP genes, are a recognized cause of female infertility; however, their pathogenic mechanisms are not fully understood. Here, we investigated how two distinct ZP defects (complete absence and thinning) compromise fertility using Zp1 mut/mut and Zp2 mut/mut rat models. We found that ZP deficiency leads to stage-specific oocyte loss during early antral follicle development in vivo and arrests the maturation of fully grown oocytes in vitro, which also exhibit reduced diameter and mitochondrial dysfunction. From the secondary follicle stage onward, granulosa cells showed reduced proliferation, increased apoptosis, and impaired adhesion, culminating in a disorganized cumulus-oocyte complex morphology and disrupted steroidogenesis by the antral stage. Further analysis revealed that the specialized structures for oocyte-somatic cell interaction, namely transzonal projections and oocyte microvilli, were disorganized and reduced in number. This structural disruption was accompanied by a global perturbation of the bidirectional communication and physical adhesion network between the oocyte and its somatic niche, underscoring the ZP’s essential role in organizing this functional microenvironment. At the molecular level, single-cell transcriptomic and protein analyses demonstrated that ZP deficiency induces a thinning of the oocyte cortical actin layer and dysregulation of cytoskeletal dynamics. This was associated with an upregulation of actin-regulating proteins, including TPM4 and ACTN1, and the engagement of focal adhesion-related pathways. The observed cortical actin disorganization provides a plausible mechanistic link to the concurrent abnormalities in microvilli and cell-cell adhesion. Collectively, our results establish the ZP as a critical structural scaffold that ensures oocyte cortical integrity and coordinates the surrounding somatic cell niche. Its disruption leads to a progressive failure in oocyte-somatic cell interaction and support, ultimately resulting in oocyte developmental impairment and loss. This study provides detailed mechanistic insights into the pathogenesis of ZP-related female infertility (particularly empty follicle syndrome).