Ti3C2T x -AuNP based paper substrates for label-free SERS detection of bacteria and multimodal antibacterials.

Bacterial infections have become a serious global health problem due to the misuse of antibiotics which causes the emergence of antibiotic-resistant strains. Photothermal therapy (PTT) has been widely studied in recent years as a method to combat the development of bacterial resistance. However, PPT may cause damage to the human body due to excessive laser power. Therefore, it is important and urgent to develop a multifunctional platform that can sensitively detect bacteria and effectively inhibit or kill bacteria at low laser power. Herein, a novel multifunctional paper substrate of Ti3C2T x -AuNP was successfully synthesized by a self-assembly and freeze-drying method for bacterial detection and photothermal sterilization at low laser power. The typical Gram-negative Escherichia coli (E. coli) and the Gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) were used as models to perform label-free, rapid and sensitive detection of bacteria based on the surface-enhanced Raman spectroscopy (SERS) method with detection limits as low as 105 CFU mL-1 and 5 × 105 CFU mL-1, respectively, demonstrating the paper substrate's ability to detect bacteria with sensitivity and accuracy. The paper substrate of Ti3C2T x -AuNP exhibits significant antibacterial effects when irradiated with 808 nm light at a low laser power of only 300 mW cm-2 and a short irradiation time of 5 minutes, and the germicidal rates for E. coli and MRSA were 99.94% and 92.71%, respectively. At the same time, the paper substrate of Ti3C2T x -AuNP also produces a variety of reactive oxygen species under 808 nm laser irradiation, resulting in photodynamic therapy (PDT). Accordingly, this paper substrate of Ti3C2T x -AuNP can not only sensitively detect bacteria, but also has photothermal and photodynamic sterilization, providing a promising countermeasure for the clinical treatment of diseases caused by multidrug-resistant bacteria.

Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis.

OBJECTIVES: Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels. METHODS: PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups. RESULTS: Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval). CONCLUSIONS: Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.

Nb2C MXene self-assembled Au nanoparticles simultaneously based on electromagnetic enhancement and charge transfer for surface enhanced Raman scattering.

Recent years, two-dimensional transition metal carbonitrides (MXene) have attracted much attention in the field of surface-enhanced Raman scattering (SERS). However, the relatively low enhancement of MXene is a major challenge. Herein, Nb2C-Au NPs nanocomposites were prepared by electrostatic self-assembly method, which have a synergistically conjugated SERS effect. The EM hot spots of Nb2C-Au NPs are significantly enlarged and expanded, while the surface Fermi level is decreased. This synergistic effect could improve the SERS performance of the system. Consequently, for the dye molecules CV and MeB, the detection limits reach 10-10 M and 10-9 M, respectively, while for biomolecule adenine, the detection limit is as low as 5 × 10-8 M. The results also show the good concentration-dependent linearity, uniformity, reproducibility and stability of SERS substrate. Nb2C-Au NPs could be a fast, sensitive and stable SERS platform for label-free and non-destructive detection. This work may expand the application of MXene based materials in the field of SERS.

Self-Assembled MXene-Au Multifunctional Nanomaterials with Various Shapes for Label-free SERS Detection of Pathogenic Bacteria and Photothermal Sterilization.

Early diagnosis of pathogenic bacteria and treatment are essential to prevent further infection. Photothermal therapy (PTT) is a promising sterilization method with advantages of minimal invasiveness and high efficiency. The effect of PTT depends on the performance of photothermal materials. Herein, Ti3C2-Au nanomaterials were prepared by the electrostatic self-assembly method, and the absorption characteristics were modulated by changing the morphology of Ti3C2-Au to achieve high photothermal conversion efficiency and sensitive label-free SERS bacterial detection. The results showed that the prepared Ti3C2-Au had better SERS performance than Au and achieved direct and sensitive detection of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Under 808 nm laser irradiation, the photothermal conversion efficiency of Ti3C2-Au nanobipyramids (NBPs) was increased to 50.41% compared with the other two composites. The bactericidal rates of Ti3C2-Au NBPs against E. coli and S. aureus were 95.11 and 99.80% in 8 min, respectively, and the killing rates of nine other bacteria were all above 95%, showing broad-spectrum antibacterial properties. Cell viability studies showed that the Ti3C2-Au NBP had significantly improved biocompatibility compared with the Au NBP and was suitable for biological applications. It can simultaneously realize sensitive bacterial detection and photothermal sterilization and is important for the detection and inhibition of pathogenic bacteria.

Effects of Inflammatory Response Genes on the Immune Microenvironment in Colorectal Cancer.

Background: The close relationship between colorectal cancer and inflammation has been widely reported. However, the relationship between colorectal cancer and inflammation at the genetic level is not fully understood. Method: From a genetic perspective, this study explored the relationship between inflammation-related genes and the immune microenvironment in colorectal cancer. We identified prognostic genes, namely CX3CL1, CCL22, SERPINE1, LTB4R, XCL1, GAL, TIMP1, ADIPOQ, and CRH, by using univariate and multivariate regression analyses. A risk scoring model for inflammatory response was established, and patients in The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were divided into two groups: high risk group and low risk group. Results: The analysis showed that the prognosis of the two groups was significantly different, and the low-risk group had a higher survival rate and longer survival time. Pathways related to apoptosis, inflammatory response, and hypoxia were significantly enriched as shown via Gene Set Enrichment Analysis (GSEA). Activated dendritic cell infiltration was found in both the TCGA and GEO databases, and the CCL21 gene played a significant role in the process of activated dendritic cell infiltration. CCL21 gene was also positively correlated with inflammatory response, and the gene expression and risk score were significantly different between the two groups. Conclusion: In summary, inflammatory response has a direct impact on patients with colorectal cancer in the prognosis and immune infiltration and further research studies on the inflammatory response can help in advancing the development of immunotherapy for colorectal cancer.

Effects of Inflammation on the Immune Microenvironment in Gastric Cancer.

BACKGROUND: Chronic inflammation and immune cell dysfunction in the tumor microenvironment are key factors in the development and progression of gastric tumors. However, inflammation-related genes associated with gastric cancer prognosis and their relationship with the expression of immune genes are not fully understood. METHOD: In this study, we established an inflammatory response model score called "Riskscore", based on differentially expressed genes in gastric cancer. We used Survival and Survminer packages in R to analyze patient survival and prognosis in risk groups. The survival curve was plotted using the Kaplan-Meier method, and the log-rank test was used to assess statistical significance, and we performed the ROC analysis using the R language package to analyze the 1-, 3-, and 5-year survival of patients in the GEO and TCGA databases. Single-factor and multi-factor prognostic analyses were carried out for age, sex, T, N, M, and risk score. Pathway enrichment analysis indicated immune factor-related pathway enrichment in both patient groups. Next, we screened for important genes that are involved in immune cell regulation. Finally, we created a correlation curve to explore the correlation between Riskscore and the expression of these genes. RESULTS: The prognosis was significantly different between high- and low-risk groups, and the survival rate and survival time of the high-risk group were lower than those of the low-risk group. we found that the pathways related to apoptosis, hypoxia, and immunity were most enriched in the risk groups. we found two common tumor-infiltrating immune cell types (i.e., follicular helper T cells and resting dendritic cells) between the two risk groups and identified 10 genes that regulate these cells. Additionally, we found that these 10 genes are positively associated with the two risk groups. CONCLUSION: Finally, a risk model of the inflammatory response in gastric cancer was established, and the inflammation-related genes used to construct the model were found to be directly related to immune infiltration. This model can improve the gastric cancer prognosis prediction. Our findings contribute to the development of immunotherapy for the treatment of gastric cancer patients.

Helicobacter pylori Infection-Related Long Non-Coding RNA Signatures Predict the Prognostic Status for Gastric Cancer Patients.

BACKGROUND: Helicobacter pylori (H. pylori) is a type I biological carcinogen, which may cause about 75% of the total incidence of gastric cancer worldwide. H. pylori infection can induce and activate the cancer-promoting signaling pathway and affect the occurrence and outcome of gastric cancer through controlling the regulatory functions of long non-coding RNAs (lncRNAs). However, we have no understanding of the prognostic worth of lncRNAs for gastric cancer patients infected with H. pylori. METHOD: We screened differentially expressed lncRNAs using DESeq2 method among TCGA database. And we built the H. pylori infection-related lncRNAs regulatory patterns. Then, we constructed H. pylori infection-based lncRNAs prognostic signatures for gastric cancer patients together with H. pylori infection, via uni-variable and multi-variable COX regression analyses. Based on receiver operator characteristic curve (ROC) analysis, we evaluated the prediction effectiveness for this model. RESULTS: We identified 115 H. pylori infection-related genes were differentially expressed among H. pylori-infected gastric cancer tissues versus gastric cancer tissues. Functional enrichment analysis implies that H. pylori infection might interfere with the immune-related pathways among gastric cancer tissues. Then, we built H. pylori infection-related dys-regulated lncRNA regulatory networks. We also identified 13 differentially expressed lncRNAs were associated with prognosis for gastric cancer patients together with H. pylori infection. Kaplan-Meier analysis demonstrated that the lncRNA signatures were correlated with the poor prognosis. What is more, the AUC of the lncRNA signatures was 0.712. Also, this prognostic prediction model was superior to the traditional clinical characters. CONCLUSION: We successfully constructed a H. pylori-related lncRNA risk signature and nomogram associated with H. pylori-infected gastric cancer patients prognosis, and the signature and nomogram can predict the prognosis of these patients.

Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment.

Background: Imbalanced nutritional supply and demand in the tumor microenvironment often leads to hypoxia. The subtle interaction between hypoxia and immune cell behavior plays an important role in tumor occurrence and development. However, the functional relationship between hypoxia and the tumor microenvironment remains unclear. Therefore, we aimed to investigate the effect of hypoxia on the intestinal tumor microenvironment. Method: We extracted the names of hypoxia-related genes from the Gene Set Enrichment Analysis (GSEA) database and screened them for those associated with colorectal cancer prognosis, with the final list including ALDOB, GPC1, ALDOC, and SLC2A3. Using the sum of the expression levels of these four genes, provided by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the expression coefficients, we developed a hypoxia risk score model. Using the median risk score value, we divided the patients in the two databases into high- and low-risk groups. GSEA was used to compare the enrichment differences between the two groups. We used the CIBERSORT computational method to analyze immune cell infiltration. Finally, the correlation between these five genes and hypoxia was analyzed. Result: The prognosis of the two groups differed significantly, with a higher survival rate in the low-risk group than in the high-risk group. We found that the different risk groups were enriched by immune-related and inflammatory pathways. We identified activated M0 macrophages in TCGA and GEO databases and found that CCL2/4/5, and CSF1 contributed toward the increased infiltration rate of this immune cell type. Finally, we observed a positive correlation between the five candidate genes' expression and the risk of hypoxia, with significant differences in the level of expression of each of these genes between patient risk groups. Conclusion: Overall, our data suggest that hypoxia is associated with the prognosis and rate of immune cell infiltration in patients with colorectal cancer. This finding may improve immunotherapy for colorectal cancer.

Immunomodulatory and antioxidant effects of total flavonoids of Spatholobus suberectus Dunn on PCV2 infected mice.

Oxidative stress plays an important role in the pathogenesis of virus infection and antioxidants are becoming promising candidates as therapeutic agents. This study is designed to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on oxidative stress in mice induced by porcine circovirus type 2 (PCV2) infection. The PCV2 infection leads to significant decrease in thymus and spleen indices, elevation of xanthine oxidase (XOD) and myeloperoxidase (MPO) activities, reduction in GSH level and GSH to GSSG ratio and decline of superoxide dismutase (SOD) activity, indicating the formation of immunosuppression and oxidative stress. TFSD treatment recovered the alteration of viscera index, antioxidant content and activities of oxidative-associated enzymes to a level similar to control. Our findings suggested that PCV2 induced immunosuppression and oxidative stress in mice and TFSD might be able to protect animals from virus infection via regulation of immune function and inhibition of oxidative stress.

Effect of total flavonoids of Spatholobus suberectus Dunn on PCV2 induced oxidative stress in RAW264.7 cells.

BACKGROUND: This study was carried out to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on PCV2 induced oxidative stress in RAW264.7 cells. METHODS: Oxidative stress model was established in RAW264.7 cells by infecting with PCV2. Virus infected cells were then treated with various concentrations (25 mg/ml, 50 mg/ml and 100 mg/ml) of TFSD. The levels of oxidative stress related molecules (NO, ROS, GSH and GSSG) and activities of associated enzymes (SOD, MPO and XOD were analyzed using ultraviolet spectrophotometry, fluorescence method and commercialized detection kits. RESULTS: PCV2 infection induced significant increase of NO secretion, ROS generation, GSSG content, activities of both XOD and MPO, and dramatically decrease of GSH content and SOD activity in RAW264.7 cells (P < 0.05). After treating with TFSD, PCV2 induced alteration of oxidative stress related molecule levels and enzyme activities were recovered to a level similar to control. CONCLUSION: Our findings indicated that TFSD was able to regulate oxidative stress induced by PCV2 infection in RAW264.7 cells, which supports the ethnomedicinal use of this herb as an alternative or complementary therapeutic drug for reactive oxygen-associated pathologies.

Inter-device reliability of the NPi-100 pupillometer.

The purpose of this study was to explore the inter-device reliability of NPi-100 pupillometers (NeuroOptics, Inc.). The pupillary examination is a fundamental element of the neurological exam. Current evidence suggests that the traditional examination of the pupil with a hand held flashlight has limited inter-rater reliability. Automated pupillometers were developed to provide an objective scoring of pupil size and reactivity. However, there are no data examining inter-device reliability of automated pupil assessments. This study included 210 paired pupillometer measurements were obtained by 33 practitioners from 20 patients at risk for cerebral edema. There was no statistically significant difference between the mean maximum pupil size at rest, the minimum pupil size during light stimulation, and the mean pupil reactivity, for both the right and left eye, when assessed by two investigators, each with a different pupillometer. In addition, Cohen's Kappa assessments of pupil size and reactivity revealed an almost perfect agreement between the two pupillometers for the maximum pupil size, the minimum pupil size, and for pupil reactivity for both eyes. There is a high inter-device reliability of automated pupillary assessments by two practitioners examining the same patient using different NPi-100 pupillometers.

Interrater Reliability of Pupillary Assessments.

BACKGROUND: Subjective scoring of pupil reactivity is a fundamental element of the neurological examination for which the pupillometer provides an objective measure. METHODS: This single-blinded observational study examined interrater reliability of pupil exam findings between two practitioners and between practitioners and a pupillometer. RESULTS: From 2329 paired assessments, the interrater reliability between practitioners was only moderate for pupil size (k = 0.54), shape (k = 0.62), and reactivity (k = 0.40). Only 33.3% of pupils scored as non-reactive by practitioners were scored as non-reactive by pupillometry. CONCLUSIONS: Despite the strong emphasis placed on the traditional pupil examination, especially for patients with a neurological illness, there is limited interrater reliability for subjective scoring of pupillary assessments. Thus, the use of automated pupillometers should be examined as a potential method to increase the reliability of measuring of pupil reactivity.

Emergency and critical care management of acute ischaemic stroke.

Ischaemic stroke is a devastating condition that is the leading cause of disability in the USA. Over the last 2 decades, the focus of management has shifted from secondary stroke prevention to acute treatment. Coordinated care starts in the field with the emergency medical service providers and continues in the ambulance and the emergency department through to the intensive care unit. After diagnosis and stabilization, a major goal is reperfusion therapy with intravenous fibrinolytics. Neuroimaging research is focused on improving patient selection, expanding treatment windows, and increasing the safety of therapeutic intervention. The role of adjunctive intra-arterial and mechanical thrombectomy remains undefined, and methods to improve reperfusion using sonolysis and new-generation fibrinolytics are currently investigational. Treatment in the intensive care unit targets prevention of secondary brain injury through optimization of blood pressure, cerebral perfusion, glucose, and temperature management, ventilation, and oxygenation. The most feared complications include malignant cerebral edema and symptomatic hemorrhagic transformation. Decompressive craniectomy is life saving, but questions regarding patient selection and timing remain. Hyperosmolar agents are currently used to mitigate cerebral edema, but newer agents to prevent the formation of cerebral edema at the molecular level are being studied. We outline a practical approach to current emergency and intensive care management based on consensus guidelines and the best available evidence.