MTHFR and MTRR gene polymorphisms in patients with chronic hepatitis B virus infections in Zigong, Sichuan Province.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a severe disease affecting the physical and economic well-being of patients. The relationship between polymorphisms in the MTHFR gene and disease progression following HBV infection remains a controversial topic. AIM: To study MTHFR and MTRR gene polymorphisms in patients with chronic HBV infections in Zigong, Sichuan Province. SUBJECTS AND METHODS: One hundred and ninety-one patients with chronic HBV infections were divided into three groups: the chronic hepatitis B (CHB) group (n = 71), the hepatitis B-induced liver cirrhosis (LC) group (n = 56), and the hepatitis B-related primary liver cancer (PLC) group (n = 64). The gene polymorphisms were detected using the PCR-melt curve method and analysed. RESULTS: The distributions of MTHFR C677T (CC: 41.2% vs. 41.8%; CT: 50% vs. 45.5%; TT: 8.8% vs. 12.7%; p = 0.714), MTHFR A1298C (AA: 70.6% vs. 72.7%; AC: 26.5% vs. 25.5%; CC: 2.9% vs. 1.8%; p = 1.000), and MTRR A66G (AA: 58.1% vs. 65.5%; AG: 39.0% vs. 29.1%; 2.9% vs. 5.5%; p = 0.353) genetic polymorphisms did not vary between male and female patients from Zigong. In addition, there were no differences in the distributions of MTHFR C677T (CC: 43.4% vs. 38.8%; CT: 49.1% vs. 48.2%; TT: 7.5% vs. 12.9%; p = 0.444), MTHFR A1298C (AA: 76.4% vs. 64.7%; AC: 20.8% vs. 32.9%; CC: 2.8% vs. 2.4%; p = 0.155), and MTRR A66G (AA: 62.3% vs. 57.6%; AG: 34.0% vs. 38.8%; 3.8% vs. 3.5%; p = 0.353) genetic polymorphisms between the patients <60 and >60 years of age. The distributions of MTHFR C677T (CHB vs. LC, p = 0.888; CHB vs. PLC, p = 0.661; PLC vs. LC, p = 0.926), MTHFR A1298C (CHB vs. LC, p = 0.12; CHB vs. PLC, p = 0.263; PLC vs. LC, p = 0.550), and MTRR A66G (CHB vs. LC, p = 0.955; CHB vs. PLC, p = 0.645; PLC vs. LC, p = 0.355) gene polymorphisms were comparable between the CHB, LC, and PLC groups. CONCLUSION: The distributions of MTHFR and MRRR genetic polymorphisms in the population with HBV infections in Zigong, Sichuan Province did not differ in age and sex. The MTHFR and MRRR genetic polymorphisms were comparable between the CHB, LC, and PLC groups.

Label-Free Imaging of Cell Apoptosis by a Light-Addressable Electrochemical Sensor.

Label-free electrochemical visualization of cancer cell apoptosis is essential for cancer therapies. In this work, we proposed a noninvasive imaging method using a light-addressable electrochemical sensor (LAES) for label-free imaging of drug-induced tumor cell apoptosis. The dynamic AC photocurrent changes on MCF-7 human breast adenocarcinoma cells after inducing by tamoxifen were imaged. And the reasons for photocurrent changes on the cells were explored by monitoring the changes in the ζ potentials of cells and Faradic impedance. The results demonstrated that the AC photocurrent on apoptotic MCF-7 cells increased, and the apoptosis degree of each cell was heterogeneous. Moreover, the AC photocurrent increase was attributed to the increased cell membrane permeability and the increased gap between the cell basal surface and the substrate caused by cell apoptosis. This study provides a brand new approach for label-free visualizing cell apoptosis heterogeneity, which has great potential in apoptosis-associated drug screening or drug efficacy evaluation.

Scanning Electrochemical Photometric Sensors for Label-Free Single-Cell Imaging and Quantitative Absorption Analysis.

A new photoelectrochemical imaging method termed scanning electrochemical photometric sensor (SEPS) is proposed in this work. It was derived from light-addressable potentiometric sensor (LAPS) and scanning photoinduced impedance microscopy (SPIM) using a front-side laser illumination at a field-effect structure. When the laser beam scans across the sensor substrate, local photocurrent changes at inversion due to the light absorption of analytes can be recorded. It will be shown that SEPS could be used for label-free living cell imaging with micro-resolution as well as real-time quantitative absorption analysis, which would broaden the applications of traditional LAPS/SPIM from potentiometric/impedance measurements to local optical analysis.

Photoelectrochemical Imaging System for the Mapping of Cell Surface Charges.

The surface charge of cells affects cell signaling, cell metabolic processes, adherence to surfaces, and cell proliferation. Our understanding of the role of membrane charges is limited due to the inability to observe changes without interfering, chemically or physically, with the cell or its membrane. Here, we report that a photoelectrochemical imaging system (PEIS) based on label-free ac-photocurrent measurements at indium tin oxide (ITO) coated glass substrates can be used to map the basal surface charge of single live cells under physiological conditions. Cells were cultured on the ITO substrate. Photocurrent images were generated by scanning a focused, modulated laser beam across the back of the ITO coated glass substrate under an applied bias voltage. The photocurrent was shown to be sensitive to the negative surface charge of the substrate facing, basal side of a single living cell-an area not accessible to other electrochemical or electrophysiological imaging techniques. The PEIS was used to monitor the lysis of mesenchymal stem cells.

Peptide Cross-Linked Poly(2-oxazoline) as a Sensor Material for the Detection of Proteases with a Quartz Crystal Microbalance.

Inflammatory conditions are frequently accompanied by increased levels of active proteases, and there is rising interest in methods for their detection to monitor inflammation in a point of care setting. In this work, new sensor materials for disposable single-step protease biosensors based on poly(2-oxazoline) hydrogels cross-linked with a protease-specific cleavable peptide are described. The performance of the sensor material was assessed targeting the detection of matrix metalloproteinase-9 (MMP-9), a protease that has been shown to be an indicator of inflammation in multiple sclerosis and other inflammatory conditions. Films of the hydrogel were formed on gold-coated quartz crystals using thiol-ene click chemistry, and the cross-link density was optimized. The degradation rate of the hydrogel was monitored using a quartz crystal microbalance (QCM) and showed a strong dependence on the MMP-9 concentration. A concentration range of 0-160 nM of MMP-9 was investigated, and a lower limit of detection of 10 nM MMP-9 was determined.

Peptide Cross-Linked Poly (Ethylene Glycol) Hydrogel Films as Biosensor Coatings for the Detection of Collagenase.

Peptide cross-linked poly(ethylene glycol) hydrogel has been widely used for drug delivery and tissue engineering. However, the use of this material as a biosensor for the detection of collagenase has not been explored. Proteases play a key role in the pathology of diseases such as rheumatoid arthritis and osteoarthritis. The detection of this class of enzyme using the degradable hydrogel film format is promising as a point-of-care device for disease monitoring. In this study, a protease biosensor was developed based on the degradation of a peptide cross-linked poly(ethylene glycol) hydrogel film and demonstrated for the detection of collagenase. The hydrogel was deposited on gold-coated quartz crystals, and their degradation in the presence of collagenase was monitored using a quartz crystal microbalance (QCM). The biosensor was shown to respond to concentrations between 2 and 2000 nM in less than 10 min with a lower detection limit of 2 nM.

Light-Addressable Potentiometric Sensors Using ZnO Nanorods as the Sensor Substrate for Bioanalytical Applications.

Light-addressable potentiometric sensors (LAPS) are of great interest in bioimaging applications such as the monitoring of concentrations in microfluidic channels or the investigation of metabolic and signaling events in living cells. By measuring the photocurrents at electrolyte-insulator-semiconductor (EIS) and electrolyte-semiconductor structures, LAPS can produce spatiotemporal images of chemical or biological analytes, electrical potentials and impedance. However, its commercial applications are often restricted by their limited AC photocurrents and resolution of LAPS images. Herein, for the first time, the use of 1D semiconducting oxides in the form of ZnO nanorods for LAPS imaging is explored to solve this issue. A significantly increased AC photocurrent with enhanced image resolution has been achieved based on ZnO nanorods, with a photocurrent of 45.7 ± 0.1 nA at a light intensity of 0.05 mW, a lateral resolution as low as 3.0 µm as demonstrated by images of a PMMA dot on ZnO nanorods and a pH sensitivity of 53 mV/pH. The suitability of the device for bioanalysis and bioimaging was demonstrated by monitoring the degradation of a thin poly(ester amide) film with the enzyme α-chymotrypsin using LAPS. This simple and robust route to fabricate LAPS substrates with excellent performance would provide tremendous opportunities for bioimaging.

LAPS and SPIM Imaging Using ITO-Coated Glass as the Substrate Material.

Light-addressable potentiometric sensors (LAPS) and scanning photo-induced impedance microscopy (SPIM) use photocurrent measurements for spatiotemporal imaging of ion concentrations, electrical potentials, and impedance. In this work, ITO-coated glass was confirmed to produce photocurrents at anodic potentials with 405 nm diode laser illumination. Therefore, it was developed as a low cost and robust substrate material for LAPS and SPIM imaging compared to traditional expensive ultrathin Si substrates. ITO showed good ac photocurrent and pH response without surface modification and insulator. Local photocurrents were produced by scanning a focused laser beam across the sample, which proved the light addressability of ITO-coated glass. With a high-impedance PMMA dot deposited onto the ITO as a model system, a lateral resolution of about 2.3 µm was achieved.

Copper Contamination of Self-Assembled Organic Monolayer Modified Silicon Surfaces Following a "Click" Reaction Characterized with LAPS and SPIM.

A copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) reaction combined with microcontact printing was used successfully to pattern alkyne-terminated self-assembled organic monolayer-modified silicon surfaces. Despite the absence of a copper peak in X-ray photoelectron spectra, copper contamination was found and visualized using light-addressable potentiometric sensors (LAPS) and scanning photo-induced impedance microscopy (SPIM) after the "click"-modified silicon surfaces were rinsed with hydrochloric acid (HCl) solution, which was frequently used to remove copper residues in the past. Even cleaning with an ethylenediaminetetraacetic acid (EDTA) solution did not remove the copper residue completely. Different strategies for avoiding copper contamination, including the use of bulky chelators for the copper(I) catalyst and rinsing with different reagents, were tested. Only cleaning of the silicon surfaces with an EDTA solution containing trifluoroacetic acid (TFA) after the click modification proved to be an effective method as confirmed by LAPS and SPIM results, which showed the expected potential shift due to the surface charge introduced by functional groups in the monolayer and allowed, for the first time, imaging the impedance of an organic monolayer.

Phytochemical profiling in single plant cell by high performance liquid chromatography-mass spectrometry.

Phytochemicals are essential secondary plant metabolites which play important roles in the areas of plant biochemistry, pharmacy and medical science because of their significant bioactivities. Conventional analysis of phytochemicals in plants needs a complex combination of different extraction and separation steps. Here a simple and universal method for profiling phytochemicals in a single plant cell was demonstrated based on high performance liquid chromatography-mass spectrometry. Single purple and colorless cell samples (about 15 µm in size) found in the outer layer of a young stem of Forsythia suspensa, just inside the cuticles were collected and transferred by glass micropipettes from cell monolayers. At least 30 peaks were separated and detected, and 24 of these peaks were identified. Apart from several common plant metabolites in high abundance, like polysaccharides and amino acids, 9 phytochemicals that have special bioactivities in this plant and in medical treatment were successfully detected. Phytochemical differences between these two kinds of cells were also distinguished which was applied to investigate the heterogeneity of cells from different parts of plants and the dependency of important plant bioprocesses on phytochemical changes.

Methylene blue as a G-quadruplex binding probe for label-free homogeneous electrochemical biosensing.

Herein, G-quadruplex sequence was found to significantly decrease the diffusion current of methylene blue (MB) in homogeneous solution for the first time. Electrochemical methods combined with circular dichroism spectroscopy and UV-vis spectroscopy were utilized to systematically explore the interaction between MB and an artificial G-quadruplex sequence, EAD2. The interaction of MB and EAD2 (the binding constant, K ≈ 1.3 × 10(6) M(-1)) was stronger than that of MB and double-stranded DNA (dsDNA) (K ≈ 2.2 × 10(5) M(-1)), and the binding stoichiometry (n) of EAD2/MB complex was calculated to be 1.0 according to the electrochemical titration curve combined with Scatchard analysis. MB was proved to stabilize the G-quadruplex structure of EAD2 and showed a competitive binding to G-quadruplex in the presence of hemin. EAD2 might mainly interact with MB, a positive ligand of G-quadruplex, through the end-stacking with π-system of the guanine quartet, which was quite different from the binding mechanism of dsDNA with MB by intercalation. A novel signal read-out mode based on the strong affinity between G-quadruplex and MB coupling with aptamer/G-quadruplex hairpin structure was successfully implemented in cocaine detection with high specificity. G-quadruplex/MB complex will function as a promising electrochemical indicator for constructing homogeneous label-free electrochemical biosensors, especially in the field of simple, rapid, and noninvasive biochemical assays.

CD16 inhibition increases host survival in a murine model of severe sepsis.

BACKGROUND: To investigate the therapeutic effect of monoclonal antibody (mAb)-induced CD16 (FcγRIII) inhibition in a murine model of high-grade (severe) sepsis. MATERIALS AND METHODS: In a prospective controlled animal study, 2 µg of CD16/32 (FcγRIII/FcγRII) or the same volume of normal saline was administered intraperitoneally to BALB/c FcγRII(-/-) mice at the time of cecal ligation and puncture (CLP) in a murine model of high-grade sepsis. Subcutaneous administration of CD16/32 (0.5 µg/24 h) or normal saline continued for 7 d. Survival was evaluated, and the underlying therapeutic mechanism of mAb-induced CD16 inhibition was investigated. RESULTS: CD16 expression was significantly increased on peripheral blood CD14(+) monocytes from mice with high-grade sepsis compared with non-septic control mice (1579.40 ± 217.75 versus 461.10 ± 36.13; P < 0.05). CD16/32 mAb treatment increased the survival of mice with high-grade sepsis (P < 0.05) and significantly decreased their elevated levels of serum tumor necrosis factor α (36.70 ± 9.97 versus 52.60 ± 10.69; P < 0.05) and interleukin 1ß (1149.40 ± 244.09 versus 2605.60 ± 353.74; P < 0.05) at 6 and 24 h after CLP, respectively. Moreover, CD16/32 mAb-treated mice with high-grade sepsis had fewer bacteria in their blood and peritoneal lavage than mice just treated with normal saline at 24 h after CLP (P < 0.05). CONCLUSIONS: CD16/32 mAb-induced CD16 inhibition increased the survival of mice with high-grade sepsis, which may have been because of the concomitant suppression of tumor necrosis factor α and interleukin 1ß as well as the enhancement of monocyte phagocytosis. Thus, targeted inhibition of CD16 can potentially improve the outcome of selected patients with severe sepsis.

One-step construction of multiplexed enzymatic biosensors using light-addressable electrochemistry on a single silicon photoelectrode.

The multiplexed detection of metabolites in parallel within a single biosensor plate is sufficiently valuable but also challenging. Herein, we combine the inherent light addressability of silicon with the high selectivity of enzymes, for the construction of multiplexed photoelectrochemical enzymatic biosensors. To conduct a stable electrochemistry and reagentless biosensing on silicon, a new strategy involving the immobilization of both redox mediators and enzymes using an amide bond-based hydrogel membrane was proposed. The membrane characterization results demonstrated a covalent coupling of ferrocene mediator to hydrogel, in which the mediator acted as not only a signal generator but also a renewable sacrifice agent. By adding corresponding enzymes on different spots of hydrogel membrane modified silicon and recording local photocurrents with a moveable light pointer, this biosensor setup was used successfully to detect multiple metabolites, such as lactate, glucose, and sarcosine, with good analytical performances. The limits of detection of glucose, sarcosine and lactate were found to be 179 µM, 16 µM, and 780 µM with the linear ranges of 0.5-2.5 mM, 0.3-1.5 mM, and 1.0-3.0 mM, respectively. We believe this proof-of-concept study provides a simple and rapid one-step immobilization approach for the fabrication of reagentless enzymatic assays with silicon-based light-addressable electrochemistry.

Acoustically Enhanced Triboelectric Stethoscope for Ultrasensitive Cardiac Sounds Sensing and Disease Diagnosis.

Electronic stethoscope used to detect cardiac sounds that contain essential clinical information is a primary tool for diagnosis of various cardiac disorders. However, the linear electromechanical constitutive relation makes conventional piezoelectric sensors rather ineffective to detect low-intensity, low-frequency heart acoustic signal without the assistance of complex filtering and amplification circuits. Herein, it is found that triboelectric sensor features superior advantages over piezoelectric one for microquantity sensing originated from the fast saturated constitutive characteristic. As a result, the triboelectric sensor shows ultrahigh sensitivity (1215 mV Pa-1) than the piezoelectric counterpart (21 mV Pa-1) in the sound pressure range of 50-80 dB under the same testing condition. By designing a trumpet-shaped auscultatory cavity with a power function cross-section to achieve acoustic energy converging and impedance matching, triboelectric stethoscope delivers 36 dB signal-to-noise ratio for human test (2.3 times of that for piezoelectric one). Further combining with machine learning, five cardiac states can be diagnosed at 97% accuracy. In general, the triboelectric sensor is distinctly unique in basic mechanism, provides a novel design concept for sensing micromechanical quantities, and presents significant potential for application in cardiac sounds sensing and disease diagnosis.

Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis.

Background: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis. Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan-Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit. Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress. Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.

Micropipet tip-based miniaturized electrochemical device combined with ultramicroelectrode and its application in immobilization-free enzyme biosensor.

In this study, a simple miniaturized microliter electrochemical device was constructed using a disposable micropipet tip and a reproducible carbon fiber ultramicroelectrode. The novel electrochemical device set the electrochemical reaction in a micropipet tip containing an ultramicroelectrode. We investigated the feasibility of the designed electrochemical device by cyclic voltammetric measurements of redox probe. Its application in an immobilization-free enzyme electrochemical biosensor was also evaluated. Horseradish peroxidase and glucose oxidase were selected to test sensor feasibility. Our results showed that the micropipet tip-based electrochemical device could detect low substrate or enzyme concentration or enzymatic reaction rate. The electrochemical device was applied to analyze the glucose content in human blood samples. With the advantages of low cost, easy operation, rapid detection and high reproducibility, this design provides a new approach in immobilization-free enzyme biosensor construction. Integrated with an ultramicroelectrode, our micropipet tip-based electrochemical device could replace most normal electrodes and electrochemical cells in common laboratories for electroanalysis.

Novel homogeneous label-free electrochemical aptasensor based on functional DNA hairpin for target detection.

We first developed a label-free and immobilization-free homogeneous electrochemical aptasensor, which combined a smart functional DNA hairpin and a designed miniaturized electrochemical device. Cocaine was chosen as a model target. The anticocaine aptamer and peroxidase-mimicking DNAzyme were integrated into one single-stranded DNA hairpin. Both aptamer and G-quadruplex were elaborately blocked by the stem region. The conformation switching induced by the affinity interaction between aptamer and cocaine released G-quadruplex part and turned on DNAzyme activity. The designed electrochemical device, constructed by a disposable micropipet tip and a reproducible carbon fiber ultramicroelectrode, was applied to the detection of homogeneous DNAzyme catalytic activity at the microliter level. The aptasensor realized the quantification of cocaine ranging from 1 to 500 µM with high specificity. The clever combination of the functional DNA hairpin and the novel device achieved an absolutely label-free electrochemical aptasensor, which showed excellent performance like low cost, easy operation, rapid detection, and high repeatability.

Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer.

BACKGROUND: Hepatitis B virus (HBV) is closely related to the occurrence and development of primary liver cancer (PLC). The early diagnosis of PLC is difficult. The study explored the clinical application value of the HBV gene basal core promoter (BCP) region 1762/1764 combined with gamma-glutamyl transpeptidase (GGT) and its isozyme II (GGTII) in PLC. METHODS: From June 2017 to June 2021, 145 hepatitis B surface antigen-positive and HBV DNA-positive patients were enrolled in the Third People Hospital of Zigong. Of them, 67 were chronic hepatitis B (CHB) patients, 30 were liver cirrhosis patients, and 48 were patients with hepatitis B-associated PLC. The HBV BCP 1762/1764 mutation was detected through the amplification refractory mutation system fluorescence PCR method, and GGTII was detected using the double-antibody sandwich method. RESULTS: The results showed that the serum GGT activity, GGTII level, aspartate aminotransferase (AST) activity, AST/alanine aminotransferase (ALT) ratio, GGT/ALT ratio, and GGT/AST ratio were significantly different between the PLC and CHB groups. Statistically significant differences in serum GGT activity, AST activity, and GGT/ALT ratio were observed between the PLC and LC groups. The BCP 1762/1764 mutation rate between the PLC and CHB groups was statistically significant. The GGTII level in the early PLC (stage I + II) group and the advanced PLC (stage III + IV) group was higher than that in the N-PLC group. Serum GGT activity in the early PLC and advanced PLC groups was higher than that in the N-PLC group. The area under the curve of the receiver operator characteristic curve of GGT and GGTII for diagnosing PLC was 0.775 (95% confidence interval [CI] [0.697, 0.854]) and 0.608 (95% CI [0.512, 0.704]), respectively. The area under curve of GGT and GGTII for diagnosing early PLC was 0.732 (95% CI [0.620, 0.845]) and 0.579 (95% CI [0.452, 0.706]), respectively. CONCLUSION: HBV gene BCP 1762/1764 mutation, GGT, and GGTII may be related to PLC occurrence. The HBV gene BCP region 1762/1764 combined with GGT has certain clinical diagnostic values for PLC and early PLC. However, GGTII is not a good indicator of early PLC and is more relevant to advanced PLC.

GENIPOSIDE IMPROVES CLP-INDUCED SEPSIS MODEL PROGNOSIS BY UPREGULATING PPARγ TO MODULATE MONOCYTE PHENOTYPE AND CYTOKINE NETWORK.

ABSTRACT: Background : We explored the efficacy and main biological mechanism of geniposide intervention in sepsis. Methods : A sepsis model was established in male BALB/c mice through cecal ligation and puncture (CLP). Different doses of geniposide (20 or 40 mg/kg) were administered intravenously at 0 and/or 24 h after CLP surgery. The survival rate of different groups was observed. In addition, the expression levels of CD16 and major histocompatibility complex class II in monocytes were assessed using flow cytometry. The concentrations of TNF-α, IL-1ß, IL-6, and IL-10 in the serum were measured by ELISA. We also observed the biological effects of geniposide on CD16 and MHC-II expression levels in RAW264.7 cells, as well as the secretion of TNF-α, IL-1ß, IL-6, and IL-10 in the LPS-induced RAW264.7 cell model. The PPARγ levels were determined using western blot analysis. Results : Intravenous administration of 40 mg/kg of geniposide at 0 h after CLP significantly improved the survival outcomes in the septic mouse model, with no significant benefits from low dosing (20 mg/kg) or delayed administration (24 h). The effective dose of geniposide significantly decreased the serum cytokine TNF-α, IL-1ß, IL-6, and IL-10 concentrations in septic mice ( P < 0.05). Notably, in vitro assays showed that geniposide specifically increased the IL-10 level. Geniposide significantly reduced the CD16 expression ( P < 0.05) and increased MHC-II expression in monocytes ( P < 0.05). In addition, geniposide elevated the PPARγ level in monocytes ( P < 0.05). Conclusions : High-dose early-stage geniposide administration significantly improved the survival rate in a CLP mouse sepsis model by modulating the monocyte phenotype and regulating the cytokine network (IL-6/IL-10 levels). The pharmacological mechanism of geniposide action might be exerted primarily through PPARγ upregulation.

Carbonized polydopamine layer-protected silicon substrates for light-addressable electrochemical sensing and imaging.

The application of silicon (Si) substrate as photoelectrode in light-addressable electrochemistry (LAE) is severely limited due to its ease of surface oxidation. The resulted silicon oxide (SiOx) layer is electronically insulating and blocks charge transfer between the electrode and electrolyte. Keeping the Si from being oxidized is a key challenge for its practical use as a semiconductor electrode. In this work, we find that by developing a thin layer of polydopamine film on the surface of Si substrate, followed by carbonization at 550 °C, the natural oxidation of Si substrate can be successfully forestalled. When applied as an electrode, it is further found that the carbonized polydopamine (cPDA) layer can also prevent anodic oxidation of Si. The cPDA layer-modified Si substrate exhibits good photoelectrochemical performance and great stability, with no obvious signal decrease under ambient environment over 32 h. Our work here provides a new modification strategy for anti-oxidation of Si substrate and it is promising in the application of light-addressable electrochemical sensing and imaging.