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Phenolic acids play an active role in protecting the intestinal barrier, the structural integrity and function of which are crucial for host health. In the present study, we aimed to identify phenolic compounds that protect the intestine and explore the underlying mechanisms. We performed an imaging-based, quantitative, high-content screening (using Caco-2 and LS174T incubated with lipopolysaccharide/palmitic acid, respectively) to identify phenolic acids that could improve the mucosal barrier. We found that chlorogenic acid (CGA), 5-caffeoylquinic acid, protocatechuic acid, and caffeic acid alleviated intestinal barrier disruption. Furthermore, CGA increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. Mechanistically, CGA inhibited the activation of myosin light chain kinase (MLCK) and Rho-associated kinase 1 (ROCK1) signals, thereby downregulating the expression of the downstream molecules phosphorylated myosin phosphatase target subunit 1 (p-MYPT1), MLCK, and phosphorylated myosin light chain (p-MLC), and upregulating the expression of tight junction proteins. In addition, CGA alleviated endoplasmic reticulum (ER) stress by inhibiting the expression levels of ER markers [glucose-regulated protein78 (GRP78) and C/EBP homologous protein (CHOP)] and the nuclear translocation of activating transcription factor 6 (ATF6), thereby promoting the expression of mucin [mucin 2 (Muc2), mucin 5AC (MUC5AC)] and secretory factor trefoil factor family 3 (TFF3) proteins. In summary, we identified four substances that can stabilise intestinal homeostasis. Of these, CGA protects the intestinal barrier by inhibiting ROCK/MLCK signalling pathways and relieving ER stress. These findings highlight the importance of rapidly screening potential active ingredients that benefit the intestinal barrier and provide a theoretical basis for enteral nutrition.

Designing amorphous/crystalline heterophase catalysts is still in the initial stage, and the study of amorphous/crystalline heterophase and carbon-free catalysts has not yet been realized. Herein, we report a unique amorphous/crystalline heterophase catalyst consisting of NiFe alloy nanoparticles (NPs) supported on Ti

The circadian rhythm of blood pressure (BP) is believed to be regulated by the clock system, which is closely linked to levels of angiotensin II (Ang II). This study aimed to investigate whether Ang II mediates the proliferation of vascular smooth muscle cells (VSMCs) through the interaction between the clock system and the mitogen-activated protein kinase (MAPK) signaling pathway. Primary rat aortic VSMCs were treated with Ang II, with or without MAPK inhibitors. VSMC proliferation, expression of clock genes, CYCLIN E, and MAPK pathways were assessed. Ang II treatment resulted in increased VSMC proliferation and rapid upregulation of clock gene Periods (Pers) expression. Compared to the non-diseased control (NC) group, VSMCs incubated with Ang II displayed a noticeable delay in the G1/S phase transition and downregulation of CYCLIN E upon silencing of Per1 and Per2 genes. Importantly, silencing Per1 or Per2 in VSMCs led to decreased expression of key MAPK pathway proteins, including RAS, phosphorylated mitogen-activated protein kinase (P-MEK), and phosphorylated extracellular signal-regulated protein kinase (P-ERK). Moreover, the MEK and ERK inhibitors, U0126 and SCH772986, significantly attenuated the Ang II-induced proliferation of VSMCs, as evidenced by an increased G1/S phase transition and decreased CYCLIN E expression. The MAPK pathway plays a critical role in regulating VSMC proliferation in response to Ang II stimulation. This regulation is controlled by the expression of circadian clock genes involved in the cell cycle. These findings provide novel insights for further research on diseases associated with abnormal VSMC proliferation.

Ultra-high-definition display technology is widely used in broadcasting, but there is a huge contradiction between its ultra-high-resolution content and short storage. Super-Resolution (SR) can effectively alleviate this contradiction. Recently, State-of-the-art image SR approaches leveraging Deep Convolutional Neural Networks (DCNNs) have demonstrated high-quality reconstruction performance. However, most of them suffer from large model parameters, which restricts their practical application. Besides, image SR for large scaling factors ( e.g. , $\times 8$ ) is a tricky issue when the parameters diminish. To remedy these issues, we propose the Lightweight Multi-scale Aggregation Network (LMAN) for the image SR, which works well for both small and large scaling factors with limited parameters. Specifically, we propose a Group-wise Multi-scale Block (GMB) in which a group convolution is exploited for extracting and fusing multi-scale features before a channel attention layer to obtain discriminative features. Additionally, we present a novel Hierarchical Spatial Attention (HSA) mechanism to jointly and adaptively fuse local and global hierarchical features for high-resolution image reconstruction. Extensive experiments illustrate that our LMAN achieves superior performance against state-of-the-art methods with similar parameters and in particular for large scaling factors such as $4\times $ and $8\times $ .