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Background Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear. Methods The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro. Results In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice. Conclusions Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases.

Anthracyclines are potent chemotherapeutics, but their clinical application is constrained by dose‐dependent cardiotoxicity, in which ferroptosis plays a critical role. Here, EBBP (Estrogen‐responsive B Box Protein) is identified as a key cardioprotective regulator in anthracycline‐induced cardiotoxicity. Transcriptomic profiling of doxorubicin (DOX)‐treated hearts reveals significant EBBP upregulation. Cardiac‐specific overexpression of EBBP protects against myocardial injury and dysfunction by reducing DOX‐induced ferroptosis. Conversely, EBBP silencing exacerbates DOX‐induced cardiac damage, an effect reversed by ferroptosis inhibitor ferrostatin‐1 (Fer‐1). The molecular targets of EBBP are subsequently identified through bulk RNA sequencing, molecular docking analysis, co‐immunoprecipitation experiments, and ubiquitination assays. Mechanistically, EBBP interacts with GRP78 to promote its K63‐linked ubiquitination, disrupting the inhibitory GRP78‐PERK interaction and activating PERK‐mediated integrated stress response (ISR). This signaling cascade ultimately leads to the activation of downstream effectors ATF4 and Nrf2, which coordinately upregulates the SLC7A11/GSH/GPX4 axis and restores iron homeostasis. Importantly, pharmacological inhibition of PERK abolishes the protective effects of EBBP against myocardial injury and ferroptosis. Overall, our findings identify EBBP as a novel suppressor of ferroptosis in anthracycline‐induced cardiotoxicity via the PERK‐mediated ISR, thereby underscoring its therapeutic potential for preventing anthracycline‐induced cardiomyopathy. EBBP expression is significantly upregulated in DOX‐treated cardiomyocytes. Mechanistically, EBBP interacts with GRP78 to mediate K63‐linked ubiquitination, thereby attenuating the inhibitory GRP78‐PERK interaction and triggering activation of the PERK‐mediated integrated stress response (ISR). This signaling cascade culminates in the activation of downstream effectors ATF4 and Nrf2, which transcriptionally upregulate the SLC7A11‐GSH‐GPX4 antioxidant axis and concurrently alleviate iron overload.

Capturing different pluripotent state stem cells from epiblast in vitro helps understand embryonic development and provides invaluable cell sources for basic research and regenerative medicine. Sheep are not only one of the most important livestock species in agriculture but also serve as an ideal preclinical model for studying human disease. Single‐cell transcriptome analysis of sheep preimplantation embryos from embryonic day (E) 1 to E14 is performed to investigate the pluripotency changes of epiblast and elucidate the pluripotent regulation signaling. By combination of growth factors or inhibitors of JAK/STAT3, FGF, WNT, and TGF‐β pathways in the culture medium, sheep formative and primed pluripotent stem cells (sfPSCs and spPSCs) are established respectively. The newly derived PSCs could maintain over 100 passages and differentiate into three germ layers. In addition, sfPSCs and spPSCs exhibit different molecular features, and sfPSCs have the ability of contribution to ICM and can be used as donor cells for producing cloned embryos efficiently. A cross‐species comparison of early embryo development in mouse, pig and sheep illustrates the conservation of the epiblast naïve to primed state transition process and the divergence of the developmental events time points, the specific gene expression patterns and pluripotent regulation signaling. These studies are expected to improve our understanding of mammal early embryo development and present a reference for defining pluripotency. This study performs a comprehensive single‐cell transcriptome analysis of sheep embryos from embryonic (E) day 1 to E14 to elucidate the mechanism of early lineage specification and the pluripotency changes (naïve, formative, and primed) of epiblast. Based on scRNA‐Seq data, culture conditions are identified and sheep stable formative and primed pluripotent stem cells (sfPSCs and spPSCs) are derived in vitro for long‐term culture. This work provides valuable data resources to investigate sheep early embryo development and broaden our understanding of livestock PSCs.

To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c-Src, and p85α were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85α, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release.

Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P<0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P<0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P<0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P<0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.

Modal crosstalk is the main bottleneck in MMF-enabled optical datacenter networks with direct detection. A novel time-slicing-based crosstalk-mitigated MDM scheme is first proposed, then theoretically analyzed and experimentally demonstrated.

Considering the robust and stable nature of the active layers, advancing the power conversion efficiency (PCE) has long been the priority for all‐polymer solar cells (all‐PSCs). Despite the recent surge of PCE, the photovoltaic parameters of the state‐of‐the‐art all‐PSC still lag those of the polymer:small molecule‐based devices. To compete with the counterparts, judicious modulation of the morphology and thus the device electrical properties are needed. It is difficult to improve all the parameters concurrently for the all‐PSCs with advanced efficiency, and one increase is typically accompanied by the drop of the other(s). In this work, with the aids of the solvent additive (1‐chloronaphthalene) and the n‐type polymer additive (N2200), we can fine‐tune the morphology of the active layer and demonstrate a 16.04% efficient all‐PSC based on the PM6:PY‐IT active layer. The grazing incidence wide‐angle X‐ray scattering measurements show that the shape of the crystallites can be altered, and the reshaped crystallites lead to enhanced and more balanced charge transport, reduced recombination, and suppressed energy loss, which lead to concurrently improved and device efficiency and stability. N2200 was utilized as a polymer acceptor in PM6:PY‐IT system and produced 16.04% power conversion efficiency for this typical all‐polymer solar cell, by suitably working with 1‐chloronaphthalene. Besides, the operation stabilities (T80) of binary additive processed devices are the best among state‐of‐the‐art polymerized small molecular acceptor‐based all‐polymer solar cells.

HighlightsA novel fluoro-methoxylated end group for Y-series acceptors is produced, and asymmetric substitution strategy is applied as a step-by-step optimization.19.24% power conversion efficiency is achieved for industrially compatible solvent ortho-xylene processed organic solar cells.Underlying morphological and photo-physical variation is revealed for device performance difference brought by solvent selection, which could set up a template for future research on similar topics.With plenty of popular and effective ternary organic solar cells (OSCs) construction strategies proposed and applied, its power conversion efficiencies (PCEs) have come to a new level of over 19% in single-junction devices. However, previous studies are heavily based in chloroform (CF) leaving behind substantial knowledge deficiencies in understanding the influence of solvent choice when introducing a third component. Herein, we present a case where a newly designed asymmetric small molecular acceptor using fluoro-methoxylated end-group modification strategy, named BTP-BO-3FO with enlarged bandgap, brings different morphological evolution and performance improvement effect on host system PM6:BTP-eC9, processed by CF and ortho-xylene (o-XY). With detailed analyses supported by a series of experiments, the best PCE of 19.24% for green solvent-processed OSCs is found to be a fruit of finely tuned crystalline ordering and general aggregation motif, which furthermore nourishes a favorable charge generation and recombination behavior. Likewise, over 19% PCE can be achieved by replacing spin-coating with blade coating for active layer deposition. This work focuses on understanding the commonly met yet frequently ignored issues when building ternary blends to demonstrate cutting-edge device performance, hence, will be instructive to other ternary OSC works in the future.

The uptake pathways of nanoplastics by edible plants have recently been qualitatively investigated. There is an urgent need to accurately quantify nanoplastics accumulation in plants. Polystyrene (PS) particles with a diameter of 200 nm were doped with the europium chelate Eu–β-diketonate (PS-Eu), which was used to quantify PS-Eu particles uptake by wheat (Triticum aestivum) and lettuce (Lactuca sativa), grown hydroponically and in sandy soil using inductively coupled plasma mass spectrometry. PS-Eu particles accumulated mainly in the roots, while transport to the shoots was limited (for example, <3% for 5,000 μg PS particles per litre exposure). Visualization of PS-Eu particles in the roots and shoots was performed with time-gated luminescence through the time-resolved fluorescence of the Eu chelate. The presence of PS-Eu particles in the plant was further confirmed by scanning electron microscopy. Doping with lanthanide chelates provides a versatile strategy for elucidating the interactions between nanoplastics and plants.The uptake and transfer of nanoplastics in the roots and shoots of lettuce and wheat were quantified by doping polystyrene nanoparticles with Eu–β-diketonate and using inductively coupled plasma mass spectrometry, time-gated luminescence and scanning electron microscopy.

Based on upper echelon theory, we employ machine learning to explore how CEO characteristics influence corporate violations using a large-scale dataset of listed firms in China for the period 2010–2020. Comparing ten machine learning methods, we find that eXtreme Gradient Boosting (XGBoost) outperforms the other models in predicting corporate violations. An interpretable model combining XGBoost and SHapley Additive exPlanations (SHAP) indicates that CEO characteristics play a central role in predicting corporate violations. Tenure has the strongest predictive power and is negatively associated with corporate violations, followed by marketing experience, education, duality (i.e., simultaneously holding the position of chairperson), and research and development experience. In contrast, shareholdings, age, and pay are positively related to corporate violations. We also analyze violation severity and violation type, confirming the role of tenure in predicting more severe and intentional violations. Overall, our findings contribute to preventing corporate violations, improving corporate governance, and maintaining order in the financial market.