Composite patch with negative Poisson's ratio mimicking cardiac mechanical properties: Design, experiment and simulation.

Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical pursuit. Currently used traditional block-shaped or mesh patches, typically incorporating a positive Poisson's ratio, often fall short of matching the deformation characteristics of cardiac tissue satisfactorily, thus often diminishing their repairing capability. By introducing auxeticity into the cardiac patches, this study is trying to present a beneficial approach to address these shortcomings of the traditional patches.

Hydrogels composite optimized for low resistance and loading-unloading hysteresis for flexible biosensors.

With the advancement of wearable and implantable medical devices, hydrogel flexible bioelectronic devices have attracted significant interest due to exhibiting tissue-like mechanical compliance, biocompatibility, and low electrical resistance. In this study, the development and comprehensive performance evaluation of poly(acrylic acid)/ N,N'-bis(acryloyl) cystamine/ 1-butyl-3-ethenylimidazol-1-ium:bromide (PAA/NB/IL) hydrogels designed for flexible sensor applications are introduced. Engineered through a combination of physical and chemical cross-linking strategies, these hydrogels exhibit strong mechanical properties, high biocompatibility, and effective sensing capabilities.

Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1.

SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides.

H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells.

The H7N9 influenza virus emerged in China in 2013, causing more than 1560 human infections, 39% of which were fatal. A 'cytokine storm' in the lungs of H7N9 patients has been linked to a poor prognosis and death; however, the underlying mechanism that triggers the cytokine storm is unknown. Here, we found that efficient replication of the H7N9 virus in mouse lungs activates gasdermin E (GSDME)-mediated pyroptosis in alveolar epithelial cells, and that the released cytosolic contents then trigger a cytokine storm.

IL-27 signaling negatively regulates FcɛRI-mediated mast cell activation and allergic response.

IL-27 is a member of the IL-12 family, exerting both anti- and pro-inflammatory activity in a cell-dependent and disease context-specific manner. Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in mast cell degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. Here, we show that the activation of mast cells is negatively regulated by IL-27 signaling.

Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response.

Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 () and transforming growth factor-β-activated kinase 1-binding protein 2 (), two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4 (TLR4) signaling pathway. We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation, and as a pro-inflammatory mediator by down-regulating SOCS1 in the later stage.

LRCH1 deficiency enhances LAT signalosome formation and CD8 T cell responses against tumors and pathogens.

CD8 T cells play pivotal roles in eradicating pathogens and tumor cells. T cell receptor (TCR) signaling is vital for the optimal activation of CD8 T cells. Upon TCR engagement, the transmembrane adapter protein LAT (linker for activation of T cells) recruits other key signaling molecules and forms the "LAT signalosome" for downstream signal transduction.

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection.

Targeting 7-Dehydrocholesterol Reductase Integrates Cholesterol Metabolism and IRF3 Activation to Eliminate Infection.

Recent work suggests that cholesterol metabolism impacts innate immune responses against infection. However, the key enzymes or the natural products and mechanisms involved are not well elucidated. Here, we have shown that upon DNA and RNA viral infection, macrophages reduced 7-dehydrocholesterol reductase (DHCR7) expression.

Rapid Evolution of H7N9 Highly Pathogenic Viruses that Emerged in China in 2017.

H7N9 low pathogenic influenza viruses emerged in China in 2013 and mutated to highly pathogenic strains in 2017, resulting in human infections and disease in chickens. To control spread, a bivalent H5/H7 inactivated vaccine was introduced in poultry in September 2017. To monitor virus evolution and vaccine efficacy, we collected 53,884 poultry samples across China from February 2017 to January 2018.

H7N9 virulent mutants detected in chickens in China pose an increased threat to humans.

Certain low pathogenic avian influenza viruses can mutate to highly pathogenic viruses when they circulate in domestic poultry, at which point they can cause devastating poultry diseases and severe economic damage. The H7N9 influenza viruses that emerged in 2013 in China had caused severe human infections and deaths. However, these viruses were nonlethal in poultry.

E3 ligase FBXW7 is critical for RIG-I stabilization during antiviral responses.

Viruses can escape from host recognition by degradation of RIG-I or interference with the RIG-I signalling to establish persistent infections. However, the mechanisms by which host cells stabilize RIG-I protein for avoiding its degradation are largely unknown. We report here that, upon virus infection, the E3 ubiquitin ligase FBXW7 translocates from the nucleus into the cytoplasm and stabilizes RIG-I.

Inhibition of ERα/ERK/P62 cascades induces "autophagic switch" in the estrogen receptor-positive breast cancer cells exposed to gemcitabine.

Several clinical trials revealed that estrogen receptor (ER) status had relevance to the response of mammary malignancy to chemotherapy. Autophagy has emerged as an important cellular mechanism of tumor cells in response to anticancer therapy. The aim of this study is to investigate whether gemcitabine induces autophagy, and more importantly, whether such autophagy is functional relevant to the therapeutic effects of gemcitabine in breast cancer cells in relation to the ER status.

MicroRNA-223 Promotes Type I Interferon Production in Antiviral Innate Immunity by Targeting Forkhead Box Protein O3 (FOXO3).

Effective recognition of viral infection and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs. Previous reports have shown that some microRNAs are induced during virus infection and participate in the regulation of the innate antiviral response. However, whether the type I IFN response is regulated by miR-223 is still unknown.

The cytoprotective role of gemcitabine-induced autophagy associated with apoptosis inhibition in triple-negative MDA-MB-231 breast cancer cells.

Triple-negative breast cancer (TNBC), which is estrogen receptor (ER)-negative, progesterone receptor‑negative and is also negative for HER2 expression, remains a great clinical challenge due to its strong resistance to chemotherapy at the late stage of treatment and relatively unfavorable prognosis. Gemcitabine has been approved by the FDA/SFDA for use as a first-line therapeutic drug against advanced or metastatic breast cancer. Therefore, the clarification of the mechanisms underlying gemcitabine-acquired resistance is of particular importance for the optimal management of TNBC.