Single-cell transcriptome analysis upon ECM-remodeling meningioma cells.

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.

A Dual-Responsive Liquid Crystal Elastomer for Multi-Level Encryption and Transient Information Display.

Information security has gained increasing attention in the past decade, leading to the development of advanced materials for anti-counterfeiting, encryption and instantaneous information display. However, it remains challenging to achieve high information security with simple encryption procedures and low-energy stimuli. Herein, a series of strain/temperature-responsive liquid crystal elastomers (LCEs) are developed to achieve dual-modal, multi-level information encryption and real-time, rewritable transient information display. The as-prepared polydomain LCEs can change from an opaque state to a transparent state under strain or temperature stimuli, with the transition strains or temperatures highly dependent on the concentration of long-chain flexible spacers. Information encrypted by different LCE inks can be decrypted under specific strains or temperatures, leading to multi-level protection of information security. Furthermore, with the combination of the phase transition of polydomain LCEs and the photothermal effect of multi-walled carbon nanotubes (MWCNTs), we achieved a repeatable transient information display by using near-infrared (NIR) light as a pen for writing. This study provides new insight into the development of advanced encryption materials with versatility and high security for broad applications.

Investigation and Analysis of Blood Biochemical Indexes and Molecular Biology of Methylmalonic Acidemia.

BACKGROUND: To compare MMA-related gene mutations in MMA children and the population in Qingdao, discuss the blood propionyl carnitine (C3), free carnitine (C0) methionine (MET), the mutual ratio and division difference in normal group, carrier group, and MMA group to analyze the relationship between some hotspot mutations and biochemical indicators. METHODS: In total 3,700 newborns testing negative in tandem mass spectrometry (MS/MS) were selected at random and submitted for testing 8 pathogenic sites in MMACHC and 10 in MMUT. The gene mutations in 84 cases with detected mutation genes and 42 diagnosed children were compared. The levels and concentration distribution of C3, C0, MET, C3/C2, C3/C0, C3/MET in the blood samples of three groups were analyzed as well as the difference of biochemical indicators in newborns with hotspot mutations (c.609A>G, c.482G>A, and c.658-660delAAG). RESULTS: All 8 pathogenic mutations in MMACHC in the population were detected and were basically consistent with the mutation types and frequency order in MMA group. The first three were c.609G>A, c.482G>A, and c.658_660delAAG. There were more types of mutation sites detected in MMA group than carrier group. Five out of 10 MMUT gene mutations were detected in the population, and 9 MMUT gene mutation sites were detected in MMA group. The findings in the two groups and the preset sites were not completely consistent. C3, C0, C3/C2, C3/C0, C3/MET in MMA group were higher than carrier and normal groups, and the difference was statistically significant; the MET in MMA group was lower than carrier and normal groups, and the difference was statistical¬ly significant. Based on the three sets of data distribution graphs, C3, C3/C2, C3/C0, and C3/MET were well distinguished. There were differences in the average C3 and C0 levels between carrier and normal groups, but with an obvious cross distribution in the graphs, and no difference in other indicators. In contrast to non-carrier group, C0, C3, C3/C0, C3/C2, and C3/MET concentration levels were higher in 609A>G mutation group, while MET level was lower, with statistical significance; in c.482G>A mutation group, C3, C3/C0, C3/C2, and C3/MET concentration levels were lower than non-carrier group, while MET level was higher, with statistical significance; in c.658-660delAAG mutation group, C0, C3, C3/C0, C3/C2, MET, and C3/MET concentration levels were not statistically different in contrast to other groups. CONCLUSIONS: The top three mutations in MMA children in Qingdao area are c.609A>G, c.482G>A, c.658-660del AAG mutations in MMAHC; C3, C3/C2, C3/C0 can be used as specific prompt indicators for MMA screening; C3, C3/C2, C3/C0, C3/MET can be used as specific prompt indicators for combined MMA screening; abnormalities in biochemical indicators in hotspot mutation group intuitively explains c.609A>G mutation and early-onset MMA. c.482G>A mutation links with late-onset MMA.

Direct Writing Large-Area Multi-Layer Ultrasmooth Films by an All-Solution Process: Toward High-Performance QLEDs.

With increasing the film area/layer, deteriorating in both smoothness and uniformity of thin-films frequently happen, which remains a barrier for making large-area quantum dot light-emitting diodes (QLEDs) by solution processes. Here, we demonstrated a facile all-solution process guided by the conical fiber array to write multi-layer ultrasmooth thin-films directly in centimeter scale. The side-by-side fibrous array helps to align surface tensions at the tri-phase contact line to facilitate large-area homogeneous deposition, which was verified by theoretical simulation. The Laplace pressure along individual conical fiber contributes to the steady liquid transfer. Thin-films with small roughness (<2.03 nm) and large-area (2×2 cm2 ) uniformity were prepared sequentially on the target substrate, leading to large-area high-performance QLEDs. The result offers new insights for fabricating large-area high-performance thin-film devices.

Characterization of the metabolites of GW1929 in rat by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

RATIONALE: GW1929 is a potent PPAR-γ activator. To fully understand its mechanism of action, it is necessary to study the in vitro and in vivo metabolism. METHODS: For in vitro metabolism, GW1929 was incubated with rat hepatocytes at 37°C for 2 h. For in vivo metabolism, rats were orally administered with GW1929 at a single dose of 10 mg/kg and plasma, urinary and fecal samples were collected at defined time points. All the samples were analyzed by the developed ultra-high-performance liquid chromatography combined with tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and product ions. RESULTS: A total of 17 metabolites, including seven glucuronide conjugates, were detected and structurally identified. M4 (hydroxylation), M13 (demethylation) and M14 (hydroxylation) were the most abundant metabolites. The metabolic pathways of GW1929 referred to hydroxylation, demethylation, deamination and glucuronidation. CONCLUSIONS: The present study provided new information on the in vitro and in vivo metabolic profiles of GW1929 which will be helpful for a better understanding of the mechanism of the elimination of GW1929.

MicroRNA-195 reverses the resistance to temozolomide through targeting cyclin E1 in glioma cells.

Glioma is the most common malignant tumor of the central nervous system with poor survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and recurrent glioma treatment with a relatively good efficacy, which exerts its antitumor effects mainly through cell death induced by DNA double-strand breaks in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits glioma patients' clinical outcome and is also an important cause of glioma replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1-phase/S-phase transition, DNA damage repair, and apoptosis of tumor cells. We found that miR-195 expression was significantly decreased in TMZ-resistant glioma cells induced with TMZ and correlated to the resistance index negatively. Also, the exogenous expression of miR-195 reversed TMZ resistance and induced the apoptosis of TMZ-resistant glioblastoma cells. Further bioinformatics analysis showed cyclin E1 (CCNE1) was a potential target gene of miR-195. Knockdown of CCNE1 partially reversed the effect of decreased miR-195 on TMZ resistance. The data from The Cancer Genome Atlas - Cancer Genome further suggested that hsa-miR-195 could negatively regulate the expression of CCNE1 in glioma. In conclusion, miR-195 reverses the resistance to TMZ by targeting CCNE1 in glioma cells and it could act as a potential target for treatment in glioma with TMZ resistance.

A Self-Healing and Shape Memory Polymer that Functions at Body Temperature.

Dual-functional polymeric system combining shape memory with self-healing properties has attracted increasingly interests of researchers, as both of these properties are intelligent and promising characteristics. Moreover, shape memory polymer that functions at human body temperature (37 °C) are desirable because of their potential applications in biomedical field. Herein, we designed a polymer network with a permanent covalent crosslinking and abundant weak hydrogen bonds. The former introduces elasticity responsible and maintain the permanent shape, and the latter contributes to the temporary shape via network rearrangement. The obtained PDMS-COO-E polymer films exhibit excellent mechanical properties and the capability to efficiently self-heal for 6 h at room temperature. Furthermore, the samples turn from a viscous state into an elastic state at 37 °C. Therefore, this polymer has shape memory effects triggered by body temperature. This unique material will have a wide range of applications in many fields, containing wearable electronics, biomedical devices, and 4D printing.

Effects of glycyrrhizin on the pharmacokinetics of puerarin in rats.

1. Puerarin has been reported to possess a wide range of pharmacological activities. This study investigated the effects of glycyrrhizin on the pharmacokinetics of puerarin in rats. 2. The pharmacokinetics of orally administered puerarin (50 mg/kg) with or without glycyrrhizin pretreatment (100 mg/kg/day for 7 days) were investigated. The plasma concentration of puerarin was determined using a sensitive and reliable LC-MS/MS method. The pharmacokinetics profiles were calculated and compared. Additionally, a Caco-2 cell transwell model was used to investigate the potential mechanism of glycyrrhizin's effects on the pharmacokinetics of puerarin. 3. The results showed that when the rats were pretreated with glycyrrhizin, the maximum concentration (Cmax) of puerarin decreased from 761.25 ± 52.34 to 456.32 ± 34.75 ng/mL, and the area under the concentration-time curve from zero to infinity (AUC0-inf) also decreased from 4142.15 ± 558.51 to 2503.74 ± 447.57 µg·h/L. The oral clearance of puerarin increased significantly from 12.20 ± 1.53 to 20.47 ± 3.25 L/h/kg (p < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizin could increase the efflux ratio of puerarin from 1.88 to 3.14. 4. In conclusion, these results indicated that glycyrrhizin could affect the pharmacokinetics of puerarin, possibly by decreasing the systemic exposure of puerarin by inducing the activity of P-gp.

Combined Blockade of T Cell Immunoglobulin and Mucin Domain 3 and Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Results in Durable Therapeutic Efficacy in Mice with Intracranial Gliomas.

BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1. The CD4+, CD8+, and regulatory T cells in brain-infiltrating lymphocytes were analyzed using flow cytometry, and the effector function of T cells was assessed using ELISA. We performed a rechallenge by subcutaneous injection of GL261 cells in the "cured" (>90 days post-orthotopic tumor implantation) and naïve mice. RESULTS The mean survival time in the control, anti-Tim-3, anti-CEACAM1, and combined treatment groups was 29.8, 43.4, 42.3, and 86.0 days, respectively, with 80% of the mice in the combined group becoming long-term survivors showing immune memory against glioma cells. Infiltrating CD4+ and CD8+ T cells increased and immunosuppressive Tregs decreased with the combined therapy, which resulted in a markedly elevated ratio of CD4+ and CD8+ cells to Tregs. Additionally, plasma IFN-γ and TGF-ß levels were upregulated and downregulated, respectively. CONCLUSIONS Our data indicate that combined blockade of Tim-3 and CEACAM1 generates robust therapeutic efficacy in mice with intracranial tumors, and provides a promising option for GBM immunotherapy.

Delayed facial palsy after tympanomastoid surgery: A report of 15 cases.

OBJECTIVE: To analyze potential etiology and outcomes of delayed facial palsy (DFP) after tympanomastoid surgery. METHODS: Fifteen cases of DFP out of 1582 cases after tympanomastoid surgery were reviewed, and the potential causes and outcomes were analyzed. RESULTS: 9 out of 15 patients (60%) had fallopian canal dehiscence and facial nerve exposure in contrast to 323 of 1567 patients (20.6%) without DFP, with significant difference (P<0.01). Chorda tympani was cut or overstretched in 4 cases. There were two cases with herpes labialis and IgM antibody against varicella-zoster virus. All patients fully recovered within two months. CONCLUSION: Fallopian canal dehiscence and facial nerve exposure was a risk factor of DFP after tympanomastoid surgery, and chorda tympani injury and viral reactivation may be triggering factors of DFP. The outcomes DFP after tympanomastoid surgery were excellent.

Bardoxolone Methyl Prevents Mesenteric Fat Deposition and Inflammation in High-Fat Diet Mice.

Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue.

Hypothalamic ghrelin signalling mediates olanzapine-induced hyperphagia and weight gain in female rats.

Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from hyperphagia.

Common ground on immune infiltration landscape and diagnostic biomarkers in diabetes-complicated atherosclerosis: an integrated bioinformatics analysis.

Introduction: Type 2 diabetes mellitus (T2DM) is a major cause of atherosclerosis (AS). However, definitive evidence regarding the common molecular mechanisms underlying these two diseases are lacking. This study aimed to investigate the mechanisms underlying the association between T2DM and AS. Methods: The gene expression profiles of T2DM (GSE159984) and AS (GSE100927) were obtained from the Gene Expression Omnibus, after which overlapping differentially expressed gene identification, bioinformatics enrichment analyses, protein-protein interaction network construction, and core genes identification were performed. We confirmed the discriminatory capacity of core genes using receiver operating curve analysis. We further identified transcription factors using TRRUST database to build a transcription factor-mRNA regulatory network. Finally, the immune infiltration and the correlation between core genes and differential infiltrating immune cells were analyzed. Results: A total of 27 overlapping differentially expressed genes were identified under the two-stress conditions. Functional analyses revealed that immune responses and transcriptional regulation may be involved in the potential pathogenesis. After protein-protein interaction network deconstruction, external datasets, and qRT-PCR experimental validation, four core genes (IL1B, C1QA, CCR5, and MSR1) were identified. ROC analysis further showed the reliable value of these core genes. Four common differential infiltrating immune cells (B cells, CD4+ T cells, regulatory T cells, and M2 macrophages) between T2DM and AS datasets were selected based on immune cell infiltration. A significant correlation between core genes and common differential immune cells. Additionally, five transcription factors (RELA, NFκB1, JUN, YY1, and SPI1) regulating the transcription of core genes were mined using upstream gene regulator analysis. Discussion: In this study, common target genes and co-immune infiltration landscapes were identified between T2DM and AS. The relationship among five transcription factors, four core genes, and four immune cells profiles may be crucial to understanding T2DM complicated with AS pathogenesis and therapeutic direction.

The role of neuropeptide Y and aquaporin 4 in the pathogenesis of intestinal dysfunction caused by traumatic brain injury.

BACKGROUND: Although the exact incidence is unknown, traumatic brain injury (TBI) can lead to intestinal dysfunction. It has important influence on the early nutrition and prognosis of TBI patients. Experiments were designed to study the roles of neuropeptide Y (NPY) and aquaporin 4 (AQP4) in the pathogenesis of intestinal dysfunction caused by TBI and to find some new solutions for the treatment of intestinal dysfunction after TBI. METHODS: Forty adult male Wistar rats were randomly divided into control, mild trauma, moderate trauma, and severe trauma groups. TBI was induced by Feeney's impact method. Control animals were sham operated but not subjected to the impact test. All rats were killed 24 h after surgery. Blood samples were obtained from the abdominal aorta for enzyme-linked immunosorbent assay measurement of NPY concentrations. Jejunum segments 15 cm distal to the Treitz ligament were taken for analysis of NPY and AQP4 expression by polymerase chain reaction, Western blot, and immunohistochemistry. Pathologic changes in intestinal cell structure and ultrastructure were studied by light microscopy and transmission electron microscopy. RESULTS: The specimens from different groups showed different degrees of structural changes, ranging from swelling and degeneration of villous epithelial cells to extensive denudation and collapse of the villi. The more severe the trauma, the more serious the degree of intestinal mucosal injury. Intestinal smooth muscle also showed varying degrees of edema and structural disorder. Electron microscopy showed that intestinal mitochondria had varying degrees of swelling and the structure of mitochondrial crista was disordered and even fractured. Plasma concentrations of NPY and jejunal gene and protein expressions of NPY and AQP4 increased significantly following TBI (P < 0.05), with greater increases at higher levels of injury. Moreover, there were positive correlations between NPY and AQP4 (P < 0.05). CONCLUSIONS: Increasing grades of TBI caused increasing degrees of intestinal ischemia and edema, and thus caused increasingly severe intestinal dysfunction. AQP4 and NPY may be involved in the pathogenesis of intestinal dysfunction after TBI. Increased NPY levels may be responsible for intestinal ischemia and hypoxia, and AQP4 may play an important role in intestinal edema. Increased NPY levels may be one of the main causes for the increase in AQP4 after TBI.

Research Progress on Mechanism and Management of Adverse Drug Reactions of Anlotinib.

Anti-angiogenesis therapy plays a vital role in the treatment of tumors, with anlotinib as its representative targeted drug. Anlotinib is a novel oral tyrosine kinase inhibitor (TKI) with inhibitory effects on tumor growth tumor angiogenesis. In Phase III clinical trials, anlotinib demonstrated better overall survival and progression-free survival than placebo in patients with advanced non-small cell lung cancer (NSCLC), and was approved for the first time as a third-line treatment for refractory advanced NSCLC. Going far beyond that, anlotinib has shown encouraging results in a variety of malignancies, including medullary thyroid carcinoma, renal cell carcinoma, gastric cancer and esophageal squamous cell carcinoma. Nevertheless, anlotinib has been subject to some controversy in terms of adverse events due to its widespread use. In this review, the mechanism of action, pharmacokinetic characteristics, adverse reactions in clinical use and management of anlotinib were summarized.

ANXA2 is a potential biomarker for cancer prognosis and immune infiltration: A systematic pan-cancer analysis.

Background: Annexin A2 (ANXA2) belongs to the Annexin A family and plays a role in epithelial-mesenchymal transition, fibrinolysis, and other physiological processes. Annexin A2 has been extensively implicated in tumorigenesis and development in previous studies, but its precise role in pan-cancer remains largely unknown. Methods: We adopted bioinformatics methods to explore the oncogenic role of Annexin A2 using different databases, including the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) biobank, the Human Protein Atlas (HPA), the Gene Expression Profiling Interaction Analysis (GEPIA) and cBioPortal. We analyzed the differential expression of Annexin A2 in different tumors and its relationship with cancer prognosis, immune cell infiltration, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI) and mismatch repair (MMR). Furtherly, we conducted a Gene Set Enrichment Analysis (GSEA) to identify the Annexin A2-related pathways. Results: Annexin A2 expression was upregulated in most cancers, except in kidney chromophobe (KICH) and prostate adenocarcinoma (PRAD). Annexin A2 showed a good diagnostic efficacy in twelve types of cancer. The high expression of Annexin A2 was significantly associated with a reduced overall survival, disease-specific survival and progression-free interval in seven cancers. The Annexin A2 expression was variably associated with infiltration of 24 types of immune cells in 32 tumor microenvironments. In addition, Annexin A2 expression was differently associated with 47 immune checkpoints, immunoregulators, DNA methylation, tumor mutation burden, microsatellite instability and mismatch repair in pan-cancer. Gene Set Enrichment Analysis revealed that Annexin A2 was significantly correlated with immune-related pathways in fifteen cancers. Conclusion: Annexin A2 widely correlates with immune infiltration and may function as a promising prognostic biomarker in many tumors, showing its potential as a target for immunotherapy in pan-cancer.

Radiotherapy combined with anti-CEACAM1 immunotherapy to induce survival advantage in glioma.

BACKGROUND: We aimed to observe the effect of radiotherapy on the expression of immune checkpoint molecule CEACAM1 in patients with glioma and the therapeutical effect of radiotherapy combined with blockade of CEACAM1 in mice with intracranial gliomas. METHODS: The expression of CEACAM1 on T-lymphocytes in the peripheral blood of patients with glioma was detected before and after radiotherapy; GL261 murine glioma cells (stably transfected with the luciferase gene) were implanted in the right caudate nucleus of C57BL/6 mice, and tumour growth was observed using the small animal in vivo imaging system. Mice were divided into 4 groups: (1) the isotype control; (2) the radiotherapy; (3) the anti-CEACAM1 treatment; and (4) the combination therapy. The survival of mice after treatment was recorded; the expression of CEACAM1 on murine glioma cells was detected by immunohistochemistry before and after radiotherapy; flow cytometry was adopted to detect CD8+ T-cells (Treg) (CD4+FoxP3+CD25+) among mouse brain-infiltrating T-cells; serum levels of IFN-γ and IL-10 were detected by ELISA; proliferation and apoptosis were observed by immunohistochemistry; Retrospective RNA-seq data analysis was conducted in a cohort of 325 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 702 patients in The Cancer Genome Atlas (TCGA) database. RESULTS: The expression of CEACAM1 on CD4+ and CD8+ T-cells in the peripheral blood of patients with glioma was significantly higher 1 week after radiotherapy than before radiotherapy and was further increased 1 month after radiotherapy. Combined therapy notably inhibited the growth of intracranial tumours in mice and prolonged their survival time, with some mice being capable of surviving long-term (> 90 d). Immunohistochemistry revealed that the expression of CEACAM1 in murine glioma tissues after radiotherapy was elevated in a time-dependent manner. Flow cytometry analysis showed an increase in mouse brain-infiltrating CD8+ T-lymphocytes, a decrease in Treg cells, and an increase in CD8+ T/Treg cells after treatment. ELISA demonstrated the elevated levels of IFN and decreased levels of IL-10 in the serum of mice in the combination therapy group. CONCLUSIONS: Radiotherapy combined with CEACAM1 inhibitors resulted in strong and durable anti-tumour immune responses against murine glioma and long-term survival of some mice. Hence, this study is expected to offer new effective immunotherapy strategies against glioma.

Mapping current status and emerging trends in NETosis: A bibliometric study.

BACKGROUND: NETosis is a critical innate immune mechanism of neutrophils that contributes to the accelerated progression of autoimmune diseases, thrombosis, cancer, and coronavirus disease 2019 (COVID-19). This study qualitatively and quantitatively analyzed the relevant literature by bibliometric methods in order to provide a more comprehensive and objective view of the knowledge dynamics in the field. METHODS: The literature on NETosis was downloaded from the Web of Science Core Collection, analyzed with VOSviewer, CiteSpace, and Microsoft for co-authorship, co-occurrence, and co-citation analysis. RESULTS: In the field of NETosis, the United States was the most influential countries. Harvard University was the most active institutions. Mariana J. Kaplan and Brinkmann V were, respectively, the most prolific and most co-cited authors. Frontiers in Immunology, Journal of Immunology, Plos One, Blood, Science, Journal of Cell Biology, and Nature Medicine were the most influential journals. The top 15 keywords are associated with immunological and NETosis formation mechanisms. The keywords with the strongest burst detection were mainly related to COVID-19 (coronavirus, ACE2, SARS coronavirus, cytokine storm, pneumonia, neutrophil to lymphocyte ratio), and cancer (circulating tumor cell). CONCLUSION: Research on NETosis is currently booming. The mechanism of NETosis and its role in innate immunity, autoimmune diseases, especially systemic lupus erythematosus and rheumatoid arthritis, and thrombosis are the focus of research in the field of NETosis. A future study will concentrate on the function of NETosis in COVID-19 and recurrent metastasis of cancer.

A variable-stiffness and healable pneumatic actuator.

Pneumatic-powered actuators are receiving increasing attention due to their widespread applications. However, their inherent low stiffness makes them incompetent in tasks requiring high load capacity or high force output. On the other hand, soft pneumatic actuators are susceptible to damage caused by over-pressuring or punctures by sharp objects. In this work, we designed and synthesized a coordination adaptable network (PETMP-AIM-Cu) with high mechanical rigidity (Young's modulus of 1.9 GPa and elongation <2% before fracturing) as well as excellent variable stiffness property (soft-rigid switching ability σ as high as 3 268 000 when ΔT = 90 °C). Combining PETMP-AIM-Cu with a self-healing elastomer based on dynamic disulfide bonds (LP-PDMS), we fabricated a new pneumatic actuator which shows high load capacity at room temperature, but can also easily deform upon heating and thus can be actuated pneumatically. Benefiting from the excellent self-healing ability of PETMP-AIM-Cu and LP-PDMS, the entire pneumatic actuator can still be actuated after being cut and healed. Such a variable-stiffness and healable pneumatic actuator would be useful for complex environmental applications.

Whole genome methylation combined with RNA-seq reveals the protective effects of Gualou-Xiebai herb pair in foam cells through DNA methylation mediated PI3K-AKT signaling pathway.

DNA methylation, including aberrant hypomethylation and hypermethylation, plays a significant role in atherosclerosis (AS); therefore, targeting the unbalanced methylation in AS is a potential treatment strategy. Gualou-xiebai herb pair (GXHP), a classic herb combination, have been used for the treatment of atherosclerotic-associated diseases in traditional Chinese medicine. However, the effects and underlying mechanism of GXHP on AS remain nebulous. In this study, the CCK-8 method was applied to determine the non-toxic treatment concentrations for GXHP. The formation of foam cells played a critical role in AS, so the foam cells model was established after RAW264.7 cells were treated with ox-LDL. The contents of total cholesterol (TC) and free cholesterol (FC) were determined by Gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was used to check the expressions of inflammatory factors including IL-1ß, TNF-α, and VCAM-1. Methyl-capture sequencing (MC-seq) and RNA-seq were applied to observe the changes in genome-wide DNA methylation and gene expression, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze differentially methylated genes (DMGs) and differentially expressed genes (DEGs). The targeted signaling pathway was selected and verified using western blotting (WB). The results showed that the lipids and inflammatory factors in foam cells significantly increased. GXHP significantly reduced the expression of TC, FC, and inflammatory factors. MC-seq and RNA-seq showed that GXHP not only corrected the aberrant DNA hypermethylation, but also DNA hypomethylation, thus restored the aberrant DEGs in foam cells induced by ox-LDL. GXHP treatment may target the PI3K-Akt signaling pathway. GXHP reduced the protein levels of phosphorylated(p)-PI3K and p-AKT in foam cells. Our data suggest that treatment with GXHP showed protective effects against AS through the inhibition of DNA methylation mediated PI3K-AKT signaling pathway, suggesting GXHP as a novel methylation-based agent.