Stabilization of Ferroelectric Hf0.5Zr0.5O2 Epitaxial Films via Monolayer Reconstruction Driven by Interfacial Redox Reaction

The binary fluorite oxide Hf0.5Zr0.5O2 tends to grab a significant amount of notice due to the distinct and superior ferroelectricity found in its metastable phase. Stabilizing the metastable ferroelectric phase and delineating the underlying growth mechanism, however, are still challenging. Recent discoveries of metastable ferroelectric Hf0.5Zr0.5O2 epitaxially grown on structurally dissimilar perovskite oxides have triggered intensive investigations on the ferroelectricity in materials that are nonpolar in bulk form. Nonetheless, the growth mechanism for the unique fluorite/perovskite heterostructures has yet to be fully explored. Here we show that the metastable ferroelectric Hf0.5Zr0.5O2 films can be stabilized even on a one-unit-cell-thick perovskite La0.67Sr0.33MnO3 buffer layer. In collaboration with scanning transmittance electron microscopy (STEM) based characterizations, we show that monolayer reconstruction driven by interfacial redox reactions plays a vital role in the formation of a unique heterointerface between the two structurally dissimilar oxides, providing the template monolayer that facilitates the epitaxial growth of the metastable HZO films. Our findings offer significant insights into the stabilization mechanism of the ferroelectric Hf0.5Zr0.5O2, and this mechanism could be extended for exploring functional metastable phases of various metal oxides

From Protein Building Blocks to Functional Materials

Proteins are the fundamental building blocks for high performance materials in nature. Such materials fulfil structural roles, as in the case of silk and collagen, and can generate active structures including the cytoskeleton. Attention is increasingly turning to this versatile class of molecules for the synthesis of next generation green functional materials for a range of applications. Protein nanofibrils are a fundamental supramolecular unit from which many macroscopic protein materials are formed. In this review, we focus on the multiscale assembly of such protein nanofibrils formed from naturally occurring proteins into new supramolecular architectures and discuss how they can form the basis of material systems ranging from bulk gels, films, fibers, micro/nanogels, condensates and active materials. We review current and emerging approaches to process and assemble these building blocks in a manner which is different to their natural evolutionarily selected role, but allows the generation of tailored functionality, with a focus on microfluidic approaches. We finally discuss opportunities and challenges for this class of materials, including applications that can be involved in this material system which consists of fully natural, biocompatible and biodegradable feedstocks yet has the potential to generate materials with performance and versatility rivalling that of the best synthetic polymers

Unraveling TIMP1: a multifaceted biomarker in colorectal cancer

Background: The pathogenic genes of colorectal cancer (CRC) have not yet been fully elucidated, and there is currently a lack of effective therapeutic targets. This study used bioinformatics methods to explore and experimentally validate the most valuable biomarkers for colorectal cancer and further investigate their potential as targets.Methods: We analyzed differentially expressed genes (DEGs) based on the Gene Expression Omnibus (GEO) dataset and screened out hub genes. ROC curve and univariate Cox analysis of The Cancer Genome Atlas (TCGA) dataset revealed the most diagnostically and prognostically valuable genes. Immunohistochemistry (IHC) experiments were then conducted to validate the expression level of these selected genes in colorectal cancer. Gene set enrichment analysis (GSEA) was performed to evaluate the enriched signaling pathways associated with the gene. Using the CIBERSORT algorithm in R software, we analyzed the immune infiltrating cell abundance in both high and low gene expression groups and examined the gene’s correlation with immune cells and immune checkpoints. Additionally, we performed drug sensitivity analysis utilizing the DepMap database, and explored the correlation between gene expression levels and ferroptosis based on the The Cancer Genome Atlas dataset.Results: The study identified a total of 159 DEGs, including 7 hub genes: SPP1, MMP1, CXCL8, CXCL1, TIMP1, MMP3, and CXCL10. Further analysis revealed TIMP1 as the most valuable diagnostic and prognostic biomarker for colorectal cancer, with IHC experiments verifying its high expression. Additionally, GSEA results showed that the high TIMP1 expression group was involved in many cancer signaling pathways. Analysis of the TCGA database revealed a positive correlation between TIMP1 expression and infiltration of macrophages (M0, M1, M2) and neutrophils, as well as the expression of immune checkpoint genes, including CTLA-4 and HAVCR2. Drug sensitivity analysis, conducted using the DepMap database, revealed that colorectal cancer cell lines exhibiting elevated levels of TIMP1 expression were more responsive to certain drugs, such as CC-90003, Pitavastatin, Atuveciclib, and CT7001, compared to those with low levels of TIMP1. Furthermore, TIMP1 expression was positively correlated with that of ferroptosis-related genes, such as GPX4 and HSPA5.Conclusion: TIMP1 can be used as a biomarker for colorectal cancer and is associated with the immunological microenvironment, drug sensitivity, and ferroptosis inhibition in this disease

Liquid–Liquid Phase‐Separated Systems from Reversible Gel–Sol Transition of Protein Microgels

Funder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269Funder: Newman FoundationFunder: BBSRC; Id: http://dx.doi.org/10.13039/501100000268Funder: Cambridge Trust; Id: http://dx.doi.org/10.13039/501100003343Funder: Jardine FoundationFunder: Trinity College CambridgeFunder: Trinity College Krishnan‐Ang StudentshipFunder: Honorary Trinity‐Henry Barlow ScholarshipFunder: China Scholarship Council; Id: http://dx.doi.org/10.13039/501100004543Funder: Herchel Smith FundsFunder: Wolfson College Cambridge Junior Research FellowshipAbstract: Liquid–liquid phase‐separated biomolecular systems are increasingly recognized as key components in the intracellular milieu where they provide spatial organization to the cytoplasm and the nucleoplasm. The widespread use of phase‐separated systems by nature has given rise to the inspiration of engineering such functional systems in the laboratory. In particular, reversible gelation of liquid–liquid phase‐separated systems could confer functional advantages to the generation of new soft materials. Such gelation processes of biomolecular condensates have been extensively studied due to their links with disease. However, the inverse process, the gel–sol transition, has been less explored. Here, a thermoresponsive gel–sol transition of an extracellular protein in microgel form is explored, resulting in an all‐aqueous liquid–liquid phase‐separated system with high homogeneity. During this gel–sol transition, elongated gelatin microgels are demonstrated to be converted to a spherical geometry due to interfacial tension becoming the dominant energetic contribution as elasticity diminishes. The phase‐separated system is further explored with respect to the diffusion of small particles for drug‐release scenarios. Together, this all‐aqueous system opens up a route toward size‐tunable and monodisperse synthetic biomolecular condensates and controlled liquid–liquid interfaces, offering possibilities for applications in bioengineering and biomedicine

Development of a monoclonal antibody to ITPRIPL1 for immunohistochemical diagnosis of non-small cell lung cancers: accuracy and correlation with CD8+ T cell infiltration

Introduction: Cancer biomarkers are substances or processes highly associated with the presence and progression of cancer, which are applicable for cancer screening, progression surveillance, and prognosis prediction in clinical practice. In our previous studies, we discovered that cancer cells upregulate inositol 1,4,5-triphosphate receptor-interacting protein-like 1 (ITPRIPL1), a natural CD3 ligand, to evade immune surveillance and promote tumor growth. We also developed a monoclonal ITPRIPL1 antibody with high sensitivity and specificity. Here, we explored the application of anti-ITPRIPL1 antibody for auxiliary diagnosis of non-small cell lung cancer (NSCLC).Methods: NSCLC patient tissue samples (n = 75) were collected and stained by anti-ITPRIPL1 or anti-CD8 antibodies. After excluding the flaked samples (n = 15), we evaluated the expression by intensity (0-3) and extent (0-100%) of staining to generate an h-score for each sample. The expression status was classified into negative (h-score < 20), low-positive (20-99), and high-positive (≥ 100). We compared the h-scores between the solid cancer tissue and stroma and analyzed the correlation between the h-scores of the ITPRIPL1 and CD8 expression in situ in adjacent tissue slices.Results: The data suggested ITPRIPL1 is widely overexpressed in NSCLC and positively correlates with tumor stages. We also found that ITPRIPL1 expression is negatively correlated with CD8 staining, which demonstrates that ITPRIPL1 overexpression is indicative of poorer immune infiltration and clinical prognosis. Therefore, we set 50 as the cutoff point of ITPRIPL1 expression H scores to differentiate normal and lung cancer tissues, which is of an excellent sensitivity and specificity score (100% within our sample collection).Discussion: These results highlight the potential of ITPRIPL1 as a proteomic immunohistochemical NSCLC biomarker with possible advantages over the existing NSCLC biomarkers, and the ITPRIPL1 antibody can be applied for accurate diagnosis and prognosis prediction

A Skin Lipidomics Study Reveals the Therapeutic Effects of Tanshinones in a Rat Model of Acne

Tanshinone (TAN), a class of bioactive components in traditional Chinese medicinal plant Salvia miltiorrhiza, has antibacterial and anti-inflammatory effects, can enhance blood circulation, remove blood stasis, and promote wound healing. For these reasons it has been developed as a drug to treat acne. The purpose of this study was to evaluate the therapeutic effects of TAN in rats with oleic acid-induced acne and to explore its possible mechanisms of action through the identification of potential lipid biomarkers. In this study, a rat model of acne was established by applying 0.5 ml of 80% oleic acid to rats’ back skin. The potential metabolites and targets involved in the anti-acne effects of TAN were predicted using lipidomics. The results indicate that TAN has therapeutic efficacy for acne, as supported by the results of the histological analyses and biochemical index assays for interleukin (IL)-8, IL-6, IL-β and tumor necrosis factor alpha. The orthogonal projection of latent structure discriminant analysis score was used to analyze the lipidomic profiles between control and acne rats. Ninety-six potential biomarkers were identified in the skin samples of the acne rats. These biomarkers were mainly related to glycerophospholipid and sphingolipid metabolism, and the regulation of their dysfunction is thought to be a possible therapeutic mechanism of action of TAN on acne