Cation Bimetallic MOF Anchored Carbon Fiber for Highly Efficient Microwave Absorption.

Carbon fiber (CF) is a potential microwave absorption (MA) material due to the strong dielectric loss. Nevertheless, owing to the high conductivity, poor impedance matching of carbon-based  materials results in limited MA performance. How to solve this problem and achieve excellent MA performance remains a principal challenge. Herein, taking full advantage of CF and excellent impedance matching of bimetallic metal-organic frameworks (MOF) derivatives layer, an excellent microwave absorber based on micron-scale 1D CF and NiCoMOF (CF@NiCoMOF-800) is developed. After adjusting the oxygen vacancies of the bimetallic MOF, the resultant microwave absorber presented excellent MA properties including the minimum reflection loss (RLmin ) of -80.63 dB and wide effective absorption bandwidth (EAB) of 8.01 GHz when its mass percent is only 5 wt.% and the thickness is 2.59 mm. Simultaneously, the mechanical properties of the epoxy resin (EP)-based coating with this microwave absorber are effectively improved. The hardness (H), elastic modulus (E), bending strength, and compressive strength of CF@NiCoMOF-800/EP coating are 334 MPa, 5.56 GPa, 82.2 MPa, and 135.8 MPa, which is 38%, 15%, 106% and 53% higher than EP coating. This work provides a promising solution for carbon materials achieving excellent MA properties and mechanical properties.

Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

Systematic optimization and evaluation of culture conditions for the construction of circulating tumor cell clusters using breast cancer cell lines.

BACKGROUND: Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. METHODS: The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. RESULTS: We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. CONCLUSIONS: The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.

Metagenomic and metabolomic analysis showing the adverse risk-benefit trade-off of the ketogenic diet.

BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.

A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

METTL3, a primary methyltransferase catalyzing the RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition. However, current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of the RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysis in vivo indicated that RSM3 induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced upon RSM3 treatment, accompanied by increased METTL3 degradation, and reduced global RNA methylation levels in two in vivo tumor models. This peptide inhibitor thus exploits a mechanism distinct from other small-molecule competitive inhibitors to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.

Identification of Potential Indicators for Survival in Patients with Thyroid Cancer Based on Expression of FAM3 Members.

Thyroid cancer (THCA) is a common head and neck malignancy. The family with sequence similarity 3 (FAM3) is a cytokine-like gene family with four members, which is presumed to participate in the development of many cancer types. However, the expression patterns of FAM3s in THCA and their prognostic values, have not yet been established. We investigated differential expressions of FAM3 mRNA and protein in THCA, then validated the findings for FAM3B by immunohistochemistry. We also investigated survival data with respect to FAM3 expression patterns in patients with THCA. FAM3s information regarding their relationships with clinical pathological parameters were obtained and FAM3 mutations were assessed. KEGG and GO pathway regarding FAM3C were obtained using online databases. To investigate potential correlations between FAM3s and immune cell infiltration, we investigated the roles of FAM3s in immune cells of patients with THCA. The mRNA expression of FAM3C were significantly elevated in THCA tissues; high expression levels of FAM3C protein were also observed in THCA tissues. A significant association between the pathological stage and the expression of FAM3C was found in patients with THCA. Patients with THCA who had high mRNA expression levels of FAM3C exhibited significantly more favorable prognosis, compared with patients who had low mRNA expression levels of FAM3C. Overall, FAM3C may play vital roles in the pathogenesis and development of THCA, and these findings constitute novel insights for biomarkers of immunotherapeutic targeted agents and may aid in the identification of prognostic biomarkers for THCA.

Secreted frizzled-related protein 5: A promising therapeutic target for metabolic diseases via regulation of Wnt signaling.

Metabolic diseases pose a significant global health challenge, characterized by an imbalance in metabolism and resulting in various complications. Secreted frizzled-related protein 5 (SFRP5), an adipokine known for its anti-inflammatory properties, has gained attention as a promising therapeutic target for metabolic diseases. SFRP5 acts as a key regulator in the Wnt signaling pathway, exerting its influence on critical cellular functions including proliferation, differentiation, and migration. Its significance extends to the realm of adipose tissue biology, where it plays a central role in regulating inflammation, insulin resistance, adipogenesis, lipid metabolism, glucose homeostasis, and energy balance. By inhibiting Wnt signaling, SFRP5 facilitates adipocyte growth, promotes lipid accumulation, and contributes to a decrease in oxidative metabolism. Lifestyle interventions and pharmacological treatments have shown promise in increasing SFRP5 levels and protecting against metabolic abnormalities. SFRP5 is a pivotal player in metabolic diseases and presents itself as a promising therapeutic target. An overview of SFRP5 and its involvement in metabolic disorders and metabolism is provided in this comprehensive review. By elucidating these aspects, valuable insights can be gained to foster the development of effective strategies in combating metabolic diseases.

Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.

As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant ß-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.

Immune infiltration and diagnostic value of immune-related genes in periodontitis using bioinformatics analysis.

BACKGROUND AND OBJECTIVES: Periodontitis, which is a chronic inflammatory periodontal disease resulting in destroyed periodontal tissue, is the leading cause of tooth loss in adults. Many studies have found that inflammatory immune responses are involved in the risk of periodontal tissue damage. Therefore, we analyzed the association between immunity and periodontitis using bioinformatics methods to further understand this disease. MATERIALS AND METHODS: First, the expression profiles of periodontitis and healthy samples were downloaded from the GEO database, including a training dataset GSE16134 and an external validation dataset GSE10334. Then, differentially expressed genes were identified using the limma package. Subsequently, immune cell infiltration was calculated by using the CIBERSORT algorithm. We further identified genes linking periodontitis and immunity from the ImmPort and DisGeNet databases. In addition, some of them were selected to construct a diagnostic model via a logistic stepwise regression analysis. RESULTS AND CONCLUSIONS: Two hundred sixty differentially expressed genes were identified and found to be involved in responses to bacterial and immune-related processes. Subsequently, immune cell infiltration analysis demonstrates significant differences in the abundance of most immune cells between periodontitis and healthy samples, especially in plasma cells. These results suggested that immunity doses play a non-negligible role in periodontitis. Twenty-one genes linking periodontitis and immunity were further identified. And nine hub genes of them were identified that may be key genes involved in the development of periodontitis. Gene ontology analyses showed that these genes are involved in response to molecules of bacterial origin, cell chemotaxis, and response to chemokines. In addition, three genes of them were selected to construct a diagnostic model. And its good diagnostic performance was demonstrated by the receiver operating characteristic curves, with an area under the curve of 0.9424 for the training dataset and 0.9244 for the external validation dataset.

Thioredoxin reductase as a novel biomarker for the diagnosis and efficacy prediction of gastrointestinal malignancy: a large-scale, retrospective study.

BACKGROUND: Our aim was to investigate the rationality and accuracy of plasma TrxR activity as an efficient tool in the early diagnosis of gastrointestinal malignancy, and whether TrxR can be used to evaluate the therapeutic efficacy of gastrointestinal malignancy. METHODS: We enrolled a total of 5091 cases, including 3736 cases in gastrointestinal malignancy, 964 in benign diseases, and 391 cases in healthy controls. We also performed receiver operating characteristic (ROC) analysis to evaluate diagnostic efficiency of TrxR. Finally, we detected pre- and post-treatment level of TrxR and common tumor markers. RESULTS: The plasma TrxR level in patients with gastrointestinal malignancy [8.4 (6.9, 9.7) U/mL] was higher than that in patients with benign disease [5.8 (4.6, 6.9) U/mL] and healthy control [3.5 (1.4, 5.4) U/mL]. Plasma TrxR showed a significant diagnostic advantage with an AUC of 0.897, compared with conventional tumor markers. In addition, the combination of TrxR and conventional tumor markers can further improve the diagnostic efficiency. We derived the optimal cut-off value of plasma TrxR as a diagnostic marker of gastrointestinal malignancy according to Youden index of 6.15 U/mL. After measuring the change trend of TrxR activity and conventional tumor markers before and after anti-tumor treatments, we found that their change trend was generally consistent, and the plasma TrxR activity was significantly decreased in patients treated with chemotherapy, targeted therapy and immunotherapy. CONCLUSIONS: Our findings recommend that plasma TrxR activity could be monitored as an efficient tool for the early diagnosis of gastrointestinal malignancy and as a feasible tool to evaluate the therapeutic effect.

Association between proteinuria and adverse pregnancy outcomes: a retrospective cohort study.

Proteinuria during pregnancy is closely related to the occurrence of adverse pregnancy outcomes. One hundred and forty-two women with proteinuria during pregnancy and followed between January 2018 and December 2020 were evaluated. Based on the 24-h proteinuria value, they were divided as mild (n = 76, 300-1000 mg/day), moderate (n = 39, 1000-3500 mg/day) and severe (n = 27, >3500 mg/day) proteinuria. The rates of prematurity, low birth weight and neonatal asphyxia were significantly higher in the severe proteinuria group than in the mild and moderate groups, while the rates of foetal growth restriction and neonatal intensive care unit admission were significantly higher in the severe compared with the mild proteinuria group (all p < .05). Logistic regression analysis showed that moderate proteinuria (OR = 97.2, 95%CI: 7.1-1334.2, p = .001) and severe proteinuria (OR = 34.0, 95%CI: 1.6-711.0, p = .023) were associated with adverse perinatal outcomes. Compared with mild proteinuria, moderate and severe proteinuria are associated with adverse pregnancy outcomes in perinatal infants.Impact StatementWhat is already known on this subject? The production of proteinuria is closely related to the filtration function of the glomerulus, the reabsorption and secretion function of the renal tubules. For women with normal renal function before pregnancy, such physiological changes are less likely to cause adverse symptoms; however, for women with chronic kidney disease before pregnancy, especially those with significantly impaired renal function, the kidneys often cannot compensate for these physiological changes, which can lead to serious complications for both mother and infant.What do the results of this study add? In our study, logistic regression analysis showed that the severity of proteinuria was independently associated with adverse perinatal outcomes. The ROC curve showed that 24-h proteinuria had a predictive value for adverse perinatal outcomes. Therefore, for patients with urine protein quantification ≥0.3 g/24 h, regular 24-h urine protein quantification during pregnancy could help predict adverse perinatal outcomes and improve prognosis.What are the implications of these findings for clinical practice and/or further research? Proteinuria quantification can be used as one of the factors predicting adverse pregnancy outcomes. Thus, monitoring of urinary protein quantification in women during pregnancy should be strengthened for early detection of renal impairment, then interventions be used to improve maternal and infant outcomes.

Prognostic risk assessment model and drug sensitivity analysis of colon adenocarcinoma (COAD) based on immune-related lncRNA pairs.

PURPOSE: The aim of this study was to identify and screen long non-coding RNA (lncRNA) associated with immune genes in colon cancer, construct immune-related lncRNA pairs, establish a prognostic risk assessment model for colon adenocarcinoma (COAD), and explore prognostic factors and drug sensitivity. METHOD: Our method was based on data from The Cancer Genome Atlas (TCGA). To begin, we obtained all pertinent demographic and clinical information on 385 patients with COAD. All lncRNAs significantly related to immune genes and with differential expression were identified to construct immune lncRNA pairs. Subsequently, least absolute shrinkage and selection operator and Cox models were used to screen out prognostic-related immune lncRNAs for the establishment of a prognostic risk scoring formula. Finally, We analysed the functional differences between subgroups and screened the drugs, and establish an individual prediction nomogram model. RESULTS: Our final analysis confirmed eight lncRNA pairs to construct prognostic risk assessment model. Results showed that the high-risk and low-risk groups had significant differences (training (n = 249): p < 0.001, validation (n = 114): p = 0.022). The prognostic model was certified as an independent prognosis model. Compared with the common clinicopathological indicators, the prognostic model had better predictive efficiency (area under the curve (AUC) = 0.805). Finally, We have analysed highly differentiated cellular pathways such as mucosal immune response, identified 9 differential immune cells, 10 sensitive drugs, and establish an individual prediction nomogram model (C-index = 0.820). CONCLUSION: Our study verified that the eight lncRNA pairs mentioned can be used as biomarkers to predict the prognosis of COAD patients. Identified cells, drugs may have an positive effect on colon cancer prognosis.

Comprehensive Analysis of Tumor Immune Microenvironment and Prognosis of m6A-Related IncRNAs in Lung Adenocarcinoma.

Lung cancer is a fatal disease with high morbidity and mortality. As a major type of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) has come into the focus of the biological and clinical research. Nevertheless, potential functions of N6-methyladenosine (m6A) methylation-related long non-coding RNAs (lncRNAs) in the tumor immune microenvironment (TIME) remain unclear. Here, we analyzed RNA-seq data of 522 samples from the TCGA-LUAD project. Based on integrative analyses of lncRNA, immune, and clinical profiles, we developed a computational method to determine the characteristics of lncRNAs as an indicators of immune cell infiltration in LUAD patients. Subsequently, we investigated the influence of m6A-related lncRNAs on prognosis and immunotherapy in patients with LUAD. We identified 24 m6A-related lncRNAs that were related to LUAD prognosis and clustered in two molecular subtypes (clusters 1 and 2). Our results suggest that cluster 1 was significantly related to downregulation of PD-L1, enhancement of immune cell infiltration, and good prognosis. Furthermore, p53 and mTOR pathways were enriched in cluster 1, whereas in the cluster 2, PPAR was uncommonly enriched. Patients with LUAD who had lower risk scores exhibited higher immunoscores and lower expression levels of programmed cell death-ligand 1, compared with patients who had higher risk scores. Finally, m6A-related lncRNAs were implicated in the TIME; our findings indicate that these lncRNAs are critical within the TIME in LUAD. These signatures are promising as potential targets for improved LUAD immunotherapy.

PDGF-BB-derived supramolecular hydrogel for promoting skin wound healing.

Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from ß-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing.

RBM38 in cancer: role and mechanism.

Cancer is the second leading cause of death globally. Abnormity in gene expression regulation characterizes the trajectory of tumor development and progression. RNA-binding proteins (RBPs) are widely dysregulated, and thus implicated, in numerous human cancers. RBPs mainly regulate gene expression post-transcriptionally, but emerging studies suggest that many RBPs can impact transcription by acting on chromatin as transcription factors (TFs) or cofactors. Here, we review the evidence that RBM38, an intensively studied RBP, frequently plays a tumor-suppressive role in multiple human cancer types. Genetic studies in mice deficient in RBM38 on different p53 status also establish RBM38 as a tumor suppressor (TS). By uncovering a spectrum of transcripts bound by RBM38, we discuss the diversity in its mechanisms of action in distinct biological contexts. Examination of the genomic features and expression pattern of RBM38 in human tissues reveals that it is generally lost but rarely mutated, in cancers. By assessing future trends in the study of RBM38 in cancer, we signify the possibility of targeting RBM38 and its related pathways as therapeutic strategies against cancer.

The drugs screened by OncoVeeTM-Mini-PDX have significantly benefited the patient with HER2-positive advanced gastric cancer.

INTRODUCTION: At present, the prognosis of HER2-positive advanced gastric cancer is extremely poor, and some patients fail to benefit from first-line Herceptin treatment, thus facing difficulties in choosing second-line drugs. CASE REPORT: Here, we report a 61-year-old male patient with HER2-positive advanced gastric cancer who is primarily resistant to Herceptin and has poor therapeutic effect. MANAGEMENT & OUTCOME: Afterwards, the OncoVeeTM-MiniPDX-guided anticancer method was used to screen drugs for second-line treatment, which resulted in liquefaction and necrosis of the patient's lesions and improved liver function indicators, as well as rapid relief of the patient's clinical symptoms. DISCUSSION: In the treatment of the Herceptin-resistant patient with advanced gastric cancer, OncoVeeTM-MiniPDX method screened drugs and brought clinical benefits.

Prevalence of Toxoplasma gondii infection in chickens in China during 1993-2021: a systematic review and meta-analysis.

Toxoplasma gondii is an important intracellular parasitic protozoan with a variety of hosts, including chickens, which poses a potential threat to public health. However, little is known regarding overall T. gondii infection in chickens in China. Herein, the prevalence and risk factors associated with T. gondii infection in chickens in China were investigated using a meta-analysis. Forty studies regarding the prevalence of T. gondii in chickens in China from 1993 to 2021 were identified using five databases (PubMed, Science Direct, CNKI, Wang Fang, and VIP). Quantitative and potential sources were analyzed through subgroup analysis and meta-regression in R v3.5.2. The overall prevalence of T. gondii in chickens in China was 13.4% (95% confidence interval (CI): 10.9-16.0). In the region subgroup, the lowest prevalence was presented in Northwestern China (6.0%, 95% CI: 3.2-9.5; P < 0.001). Seasonally, T. gondii prevalence was the highest in spring (17.9%, 95% CI: 7.7-30.9; P = 0.007). Among detection methods, the prevalence in the ELISA subgroup was the highest (22.8%, 95% CI: 17.1-29.1; P < 0.001). According to the farming mode, the prevalence of T. gondii in free-range chickens (19.5%, 95% CI: 15.4-23.9) was significantly higher than that in chickens raised by intensive farming (7.4%, 95% CI: 5.1-10.2; P < 0.001). We also estimated the relationships between region, sampling year, chicken age, chicken application, gender, sample classification, study quality, and T. gondii prevalence in chickens in China. Our study showed that region, season, and farming model played important roles in T. gondii infection of chickens. Integrated control measures should be undertaken to reduce the losses caused by T. gondii infection to the chicken industry.

Redox-Regulated Conformational Change of Disulfide-Rich Assembling Peptides.

Disulfide bond formation is a common mechanism for regulating conformational changes in proteins during oxidative folding. Despite extensive studies of the use of multiple disulfide bonds to constrain peptide conformation, few studies have explored their usage in developing self-assembling peptides. Herein, we report that a thiol-rich peptide could fold into an amphiphilic ß-hairpin conformation through the formation of two hetero-disulfide bonds upon oxidation, subsequently self-assembling into a mechanically rigid hydrogel. Breaking disulfide bonds under reductive condition, the hydrogel exhibited a transition from hydrogel to solution. Molecular simulation revealed that intermolecular interaction between two tryptophan residues was indispensable for hydrogelation. This work is the first case of the use of multiple disulfide bonds to control conformational change and self-assembly, and provides a cell-compatible hydrogel material for potential biomedical application.

Copper coating formed by micro-arc oxidation on pure Mg improved antibacterial activity, osteogenesis, and angiogenesis in vivo and in vitro.

Micro-arc oxidation (MAO) was used to improve the resistance of pure magnesium (Mg). Copper (Cu), a good antibacterial, angiogenic, and osteogenic element, was added by reaction in a Cu-containing electrolyte to improve the osteogenic and pro-angiogenic activities of Mg. The surface microstructures of the resulting MAO were evaluated by a scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) mapping. The release of Cu ions was detected by ICP-OES. The antibacterial activity of films with different concentrations of Cu ions was assessed against Staphylococcus aureus (S. aureus). The osteogenesis of films was confirmed by cell morphology and proliferation, ALP activity, alizarin red staining, and osteogenic-related gene expression in the MC3T3-E1 cell line. The angiogenesis of the films was tested in human umbilical vein endothelial cells (HUVECs) by cell migration, tube formation, and VEGF quantification in vitro, and by a chicken embryo chorioallantoic membrane (CAM) assay in vivo. The results showed that the microporous structure was shaped by MAO, and the Cu group was denser and more uniform. The Cu coating showed effective antibacterial activity against S. aureus while also enhancing osteogenesis and angiogenesis in vitro. According to the CAM assay, the Cu group showed not only biocompatibility but also a significant angiogenic response, which was consistent with in vitro studies. The findings indicate that a Cu coating on Mg-MAO enhances osteogenesis and angiogenesis.

ROR2 promotes the epithelial-mesenchymal transition by regulating MAPK/p38 signaling pathway in breast cancer.

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a tyrosine-protein kinase receptor highly implicated in the growth plate and cartilage development, which may be involved in epithelial-mesenchymal transition (EMT) in breast cancer (BC) cells. Although ROR2 is known to promote the migration of BC cells, the detailed mechanism of this event is still not clear. Here, we found that ROR2 expression was significantly increased in BC lymphatic metastatic tissue as well as BC samples compared to normal adjacent breast tissues. A higher expression of ROR2 in MDA-MB-231 and a lower expression of ROR2 in MCF-7 cells were observed. MDA-MB-231-siROR2 cells with ROR2 knockdown inhibited MDA-MB-231 cell invasion, migration, and clonal formation, while MCF-7-OvROR2 cells with overexpression showed the opposite results. The underlying mechanisms involved in ROR2-induced EMT in MDA-MB-231 and MCF-7 cells were further investigated. ROR2 may activate EMT progression in BC cells by altering MAPK kinase 3/6 (MKK3/6) expression. The expressions of transforming growth factor-ß, matrix metalloproteinase-2 (MMP-2), and MMP-9, which were related to tumor cell invasion activities, were notably increased in MCF-7-OvROR2 cells. The EMT markers, including snail, N-cadherin, tissue inhibitor of metalloproteinases-1, and vimentin, were significantly upregulated in MCF-7-OvROR2 cells. On the contrary, E-cadherin was obviously reduced expressed in MCF-7-OvROR2 cells. ROR2 may regulate the malignant phenotype of BC cells possibly via activation of mitogen-activated protein kinase (MAPK)/p38 signaling pathway. Collectively, ROR2 promotes BC carcinogenesis by mediating the MAPK/p38 pathway, which is independent of Wnt5α.