Plug-and-play smart transistor bio-chips implementing point-of-care diagnosis of AMI with modified CRISPR/Cas12a system.

The point-of-care diagnosis of acute myocardial infarction (AMI), an extremely lethal disease with only a few hours of golden rescue time, is significant and urgently required. Here, we describe a plug-and-play carbon nanotube field effect transistor (CNT-FET) bio-chip supported with a smart portable readout for ultrasensitive and on-site testing of cardiac troponin I (cTnI), which is one of the most specific and valuable biomarkers of AMI. A modified clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system, featuring the G-triplex structured reporter, was first combined with the CNT-FET to realize non-nucleic acid detection. Such a unique CNT-FET biosensor achieved the high sensitivity (LOD: 0.33 fg/mL), which is expected to give timely warning in the early stage of myocardial injury. In addition, a bilayer gate dielectric consisting of Y2O3/HfO2, employed into the passivation process, enabled the high environmental stability and repeatability of CNT-FET. More importantly, the homemade compact chip readout forged a field-deployable cTnI analytical tool, realizing "plasma-to-answer" performance for AMI patients in point-of-care testing scenarios. The developed technology holds promise to help doctors make clinical decisions faster, especially in remote areas.

Functionalized carbon nanotube field-effect transistor biosensor for highly sensitive detection of exosomal protein.

Since the exosomal protein level is related to many diseases, sensitive detection of exosomal protein is highly desirable. Here, we describe a polymer-sorted high-purity semiconducting carbon nanotubes (CNTs) films-based field-effect transistor (FET) biosensor for ultrasensitive and label-free detection of MUC1, a transmembrane protein highly expressed in breast cancer exosomes. Polymer-sorted semiconducting CNTs hold advantages including high purity (>99%), high CNT concentration, and short processing time (<1 h), but they are difficult to be stably functionalized with biomolecules because of lacking hanging bonds on their surface. To solve this issue, poly-lysine (PLL) was employed to modify the CNT films after they were deposited on the sensing channel surface of the fabricated FET chip. To specifically recognize the exosomal protein, sulfhydryl aptamer probes were immobilized on the gold nanoparticles (AuNPs) surface that was assembled on PLL substrate. The aptamer-modified CNT FET was capable of sensitively and selectively detecting exosomal MUC1 as high as 0.34 fg/mL. Moreover, the CNT FET biosensor was able to recognize breast cancer patients from healthy individuals by comparing the expression level of exosomal MUC1. The developed CNT FET biosensor is expected to be a novel assay for early diagnosis of cancer.

Nanosensor-Driven Detection of Neuron-Derived Exosomal Aß42 with Graphene Electrolyte-Gated Transistor for Alzheimer's Disease Diagnosis.

Blood-based tests have sparked tremendous attention in non-invasive early diagnosis of Alzheimer's disease (AD), a most prevalent neurodegenerative malady worldwide. Despite significant progress in the methodologies for detecting AD core biomarkers such as Aß42 from serum/plasma, there remains cautious optimism going forward due to its controversial diagnostic value and disease relevance. Here, a graphene electrolyte-gated transistor biosensor is reported for the detection of serum neuron-derived exosomal Aß42 (NDE-Aß42), which is an emerging, compelling trove of blood biomarker for AD. Assisted by the antifouling strategy with the dual-blocking process, the noise against complex biological background was considerably reduced, forging an impressive sensitivity gain with a limit of detection of 447 ag/mL. An accurate detection of SH-SY5Y-derived exosomal Aß42 was also achieved with highly conformable enzyme-linked immunosorbent assay results. Importantly, the clinical analysis for 27 subjects revealed the immense diagnostic value of NDE-Aß42, which can outclass that of serum Aß42. The developed electronic assay demonstrates, for the first time, nanosensor-driven NDE-Aß42 detection, which enables a reliable discrimination of AD patients from non-AD individuals and even the differential diagnosis between AD and vascular dementia patients, with an accuracy of 100% and a Youden index of 1. This NDE-Aß42 biosensor defines a robust approach for blood-based confident AD ascertain.

Tandem Cas13a/crRNA-Mediated CRISPR-FET Biosensor: A One-for-All Check Station for Virus without Amplification.

The path toward field-effect transistor (FET) application from laboratory to clinic has delivered a compelling push in the biomedical domain, yet ultrasensitive and timely pathogen identification without PCR remains a long-lasting challenge. Herein, we create a generic check station termed "CRISPR-FET", first incorporating the CRISPR/Cas13a system within the FET modality, for accelerated and unamplified detection of viral RNA. Unlike conventional FETs bearing target-specific receptors, this sensor holds three unique advancements: (i) an ingenious sensing mechanism is used, which converts the signal of a large-sized analyte into an on-chip cleavage response of an immobilized CRISPR reporter, enabling signal generation events to occur all within the Debye length; (ii) the multipurpose inspection of the CoV ORF1ab, CoV N gene, and HCV RNA unveils the potential for "one-for-all" scalable FET-based molecular diagnostics; and (iii) it is shown that Cas13a-crRNAs targeting different sites of the viral genome can be deployed in tandem to amplify the FET response, empowering the detection limit down to 1.56 aM, which is a world-record level of sensitivity in the FET for direct viral gene sensing. Notably, a brilliant clinical applicability was made in distinguishing HCV-infected patients from normal controls. Overall, this study sheds new insights into FET-based nucleic acid sensing technology and invokes a vision for its possible future roles in diagnosis of various viral diseases.

A better overall survival (OS) for total (ipsilateral) retroperitoneal lipectomy than standard complete resection in patients with retroperitoneal liposarcoma: a comparative multi-institutional study.

Background: Complete resection (CR) serves as the standard of surgical treatment for retroperitoneal liposarcoma (RPLS). Unfortunately, even at referral centers, recurrence rates are high, and CR may not address multifocal diseases, which are a common phenomenon in RPLS. We sought to retrospectively compare the clinical outcomes of RPLS patients treated with total (ipsilateral) retroperitoneal lipectomy (TRL) and CR. Because TRL remove potentially multifocal tumors in the fat, patients may have a better prognosis than CR. Methods: Patients with primary/first-recurrent RPLS who had been treated at 5 referral centers were recruited from December 2014 to June 2018. Multivariable Cox regression analyses were conducted to determine the effects of demographic, operative, and clinicopathological variables on the following primary endpoints: local recurrence (LR), local recurrence-free survival (LRFS), and overall survival (OS). Results: A total of 134 patients were enrolled in this retrospective study, 53 of whom underwent TRL, and 81 of whom underwent CR. The 2 groups were comparable in terms of age, gender, presentation (primary vs. first-recurrent RPLS), number of tumors (unifocal vs. multifocal) at presentation, and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade. The TRL group had higher levels of preoperative hemoglobin (Hb) (13 vs. 12.5 g/dL; P=0.008) and a lower amount of intraoperative blood loss (400 vs. 500 mL; P=0.034), but there were no significant differences in the length of hospital stay (23 vs. 22 d; P=0.47) or complications (32 vs. 30; P=0.82) between the 2 groups. In a subset of patients with multifocal tumors at initial presentation, OS was more prolonged in those treated with TRL than those treated with CR (P=0.0272). Based on the multivariable analysis, primary liposarcoma and a low FNCLCC grade were associated with decreased LR and improved OS. Conclusions: TRL is a safe procedure that positively affects the OS of patients with multifocal RPLS. This novel strategy deserves further investigation in prospective studies.

Ultrasensitive detection of exosomal miRNA with PMO-graphene quantum dots-functionalized field-effect transistor biosensor.

Compared with the conventional DNA probe immobilization on the planar surface, nanoparticles-based DNA probes enable more RNA molecules to be anchored to the sensor surface, thereby improving the detection sensitivity. In this work, we report phosphorodiamidate morpholino oligomers (PMO)-graphene quantum dots (GQDs)-functionalized reduced graphene oxide (RGO) field effect transistor (FET) biosensors for ultrasensitive detection of exosomal microRNAs. After the RGO FET sensor was fabricated, polylysine (PLL) film was deposited onto the RGO surface. GQDs-PMO hybrid was prepared and covalently bound to PLL surface, enabling detection of exosomal microRNAs (miRNAs). The method achieved a detection limit as low as 85 aM and high specificity. Furthermore, the FET sensor was able to detect exosomal miRNAs in plasma samples and distinguish breast cancer samples from healthy samples. Compared with other methods, we use GQDs to further improve the sensitivity of FET, making it a potential tool for early diagnosis of breast cancer.

Carbon Nanotube Field-Effect Transistor Biosensor for Ultrasensitive and Label-Free Detection of Breast Cancer Exosomal miRNA21.

Tumor-derived exosomal miRNAs may have important functions in the onset and progression of cancers and are potential biomarkers for early diagnosis and prognosis monitoring. Yet, simple, sensitive, and label-free detection of exosomal miRNAs remains challenging. Herein, an ultrasensitive, label-free, and stable field-effect transistor (FET) biosensor based on a polymer-sorted high-purity semiconducting carbon nanotube (CNT) film is reported to detect exosomal miRNA. Different from conventional CNT FETs, the CNT FET biosensors employed a floating gate structure using an ultrathin Y2O3 as an insulating layer, and assembled Au nanoparticles (AuNPs) on Y2O3 as linkers to anchor probe molecules. A thiolated oligonucleotide probe was immobilized on the AuNP surface of the sensing area, after which miRNA21 was detectable by monitoring the current change before and after hybridization between the immobilized DNA probe and target miRNA. This method achieved both high sensitivity (LOD: 0.87 aM) and high specificity. Furthermore, the FET biosensor was employed to test clinical plasma samples, showing significant differences between healthy people and breast cancer patients. The CNT FET biosensor shows the potential applications in the clinical diagnosis of breast cancer.

Rapid and unamplified identification of COVID-19 with morpholino-modified graphene field-effect transistor nanosensor.

SARS-CoV-2 RNA is identified as a pivotal player to bolster energizing zones of COVID-19 detection. Herein, we develop a rapid and unamplified nanosensing platform for detection of SARS-CoV-2 RNA in human throat swab specimens. A gold nanoparticle (AuNP)-decorated graphene field-effect transistor (G-FET) sensor was fabricated, after which complementary phosphorodiamidate morpholino oligos (PMO) probe was immobilized on the AuNP surface. This sensor allowed for highly sensitive testing of SARS-CoV-2 RdRp as PMO does not have charges, leading to low background signal. Not only did the method present a low limit of detection in PBS (0.37 fM), throat swab (2.29 fM), and serum (3.99 fM), but also it achieved a rapid response to COVID-19 patients' samples within 2 min. The developed nanosensor was capable of analyzing RNA extracts from 30 real clinical samples. The results show that the sensor could differentiate the healthy people from infected people, which are in high agreement with RT-PCR results (Kappa index = 0.92). Furthermore, a well-defined distinction between SARS-CoV-2 RdRp and SARS-CoV RdRp was also made. Therefore, we believe that this work provides a satisfactory, attractive option for COVID-19 diagnosis.

Topological flat bands in twisted trilayer graphene.

Twisted trilayer graphene (TLG) may be the simplest realistic system so far, which has flat bands with nontrivial topology. Here, we give a comprehensive calculation about its band structures and the band topology, i.e., valley Chern number of the nearly flat bands, with the continuum model. With realistic parameters, the magic angle of twisted TLG is about 1.12°, at which two nearly flat bands appears. Unlike the twisted bilayer graphene, a small twist angle can induce a tiny gap at all the Dirac points, which can be enlarged further by a perpendicular electric field. The valley Chern numbers of the two nearly flat bands in the twisted TLG depends on the twist angle θ and the perpendicular electric field E⊥. Considering its topological flat bands, the twisted TLG should be an ideal experimental platform to study the strongly correlated physics in topologically nontrivial flat band systems. And, due to its reduced symmetry, the correlated states in twisted TLG should be quite different from that in twisted bilayer graphene and twisted double bilayer graphene.

Dual-Aptamer Modified Graphene Field-Effect Transistor Nanosensor for Label-Free and Specific Detection of Hepatocellular Carcinoma-Derived Microvesicles.

Cancerous microvesicles (MVs), which are heterogeneous membrane-bound nanovesicles shed from the surfaces of cancer cells into the extracellular environment, have been widely recognized as promising "biofingerprints" for various cancers. High-performance identification of cancerous MVs plays a vital role in the early diagnosis of cancer, yet it is still technically challenging. Herein, we report a gold nanoparticle (AuNP)-decorated, dual-aptamer modified reduced graphene oxide (RGO) field-effect transistor (AAP-GFET) nanosensor for the label-free, specific, and sensitive quantification of HepG2 cell-derived MVs (HepG2-MVs). After GFET chips were fabricated, AuNPs were then decorated on the RGO surface. For specific capture and detection of HepG2-MVs, both sulfhydrylated HepG2 cell specific TLS11a aptamer (AptTLS11a) and epithelial cell adhesion molecule aptamer (AptEpCAM) were immobilized on the AuNP surface through an Au-S bond. This developed nanosensor delivered a broad linear dynamic range from 6 × 105 to 6 × 109 particles/mL and achieved a high sensitivity of 84 particles/µL for HepG2-MVs detection. Moreover, this AAP-GFET platform was able to distinguish HepG2-MVs from other liver cancer-related serum proteins (such as AFP and CEA) and MVs derived from human normal cells and other cancer cells of lung, pancreas, and prostate, suggesting its excellent method specificity. Compared with those modified with a single type of aptamer alone (AptTLS11a or AptEpCAM), such an AAP-GFET nanosensor showed greatly enhanced signals, suggesting that the dual-aptamer-based bio-nano interface was uniquely designed and could realize more sensitive quantification of HepG2-MVs. Using this platform to detect HepG2-MVs in clinical blood samples, we found that there were significant differences between healthy controls and hepatocellular carcinoma (HCC) patients, indicating its great potential in early HCC diagnosis.

Microvesicle detection by a reduced graphene oxide field-effect transistor biosensor based on a membrane biotinylation strategy.

Unlike other extracellular vesicle (EV) subtypes such as exosomes, the lack of well-defined universal markers on the surface of microvesicles (MVs) has led to difficulty in the detection of the entire MV population. To design a universal MV detection method, we reported highly sensitive electrical detection of MVs using a reduced graphene oxide (RGO)-based field-effect transistor (FET) biosensor by the introduction of a membrane biotinylation strategy in this work. Biotinylated MVs (B-MVs) were obtained by supplying the culture medium with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethylene glycol)-2000] (DSPE-PEG-biotin) while cultivating the cells. Excellent biotinylation efficiency of MVs (92.6%) was then realized. A streptavidin (SA) probe was subsequently modified onto the channel surface of the as-fabricated RGO-based FET device, which was capable of specifically recognizing B-MVs due to the high affinity between SA and biotin in a 1 : 4 recognition format. The results showed that the RGO-based FET biosensor could detect B-MVs in a wide range from 105 particles per mL to 109 particles per mL with a low detection limit down to 20 particles per µL, which was the lowest value compared with other previously reported results. This platform also allowed distinguishing B-MVs from other unbiotinylated EV types such as MVs and exosomes, exhibiting excellent specificity. Moreover, this FET biosensor demonstrated the capability of detecting B-MVs derived from different cell lines including cancer cells and normal cells, indicating its versatility and potential applications in the biomedical field.

Electrical and Label-Free Quantification of Exosomes with a Reduced Graphene Oxide Field Effect Transistor Biosensor.

Exosomes are small membrane-bound nanovesicles with a size of 50-150 nm which contain many functional biomolecules, such as nucleic acids and proteins. Due to their high homology with parental generation, they are of great significance in clinical diagnosis. At present, the quantitative detection of low concentrations of cancer-derived exosomes present in biofluids is still a great challenge. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a reduced graphene oxide (RGO) field effect transistor (FET) biosensor. An RGO FET biosensor modified with specific antibody CD63 in the sensing area was fabricated and was used for electrical and label-free quantification of exosomes. The method achieved a low limit of detection down to 33 particles/µL, which is lower than that of many other available methods. In addition, the FET biosensor was employed to detect exosomes in clinical serum samples, showing significant differences in detecting healthy people and prostate cancer (PCa) patients. Different from other technologies, this study provides a unique technology capable of directly quantifying exosomes without labeling, indicating its potential as a tool for early diagnosis of cancer.

Receptor-Mediated Field Effect Transistor Biosensor for Real-Time Monitoring of Glutamate Release from Primary Hippocampal Neurons.

Glutamate, one of the most important central excitatory neurotransmitters, plays crucial roles in nerve signal transduction and is implicated in several neurological disorders. However, no effective means has been developed for specific detection of glutamate released from primary cultured neurons. Here we present a reduced graphene oxide (RGO)-based field effect transistor (FET) biosensor functionalized with synthesized glutamate receptor for real-time monitoring of glutamate release from primary cultured rat hippocampus neurons. Metabotropic glutamate receptors (mGluR) was specifically synthesized and then immobilized on the RGO surface by 1-pyrenebutanoic acid succinimidyl ester (PASE) linker, after which target glutamate (pI = 3.22) could specifically bind to the synthesized mGluR in the neutral buffer, causing the charge density change. After the neurons were cultured on the sensing channel with a self-made liquid reservoir, the FET biosensor could discriminate glutamate in the femtomolar range in complete cell culture medium and generate encouraging results in real-time monitoring of glutamate release from primary rat hippocampus neurons. This work is the first report of specific and direct detection of glutamate molecules released from primary culture of differentiated central neurons, which may further help understand the nature of neuronal communication. Moreover, this work paves a way for the detection of electrochemically inactive small molecules released by cells.

A field effect transistor modified with reduced graphene oxide for immunodetection of Ebola virus.

The authors describe a field effect transistor (FET) based immunoassay for the detection of inactivated ebola virus (EBOV). An equine antibody against the EBOV glycoprotein was immobilized on the surface of the FET that was previously modified with reduced graphene oxide (RGO). The antibody against EBOV was immobilized on the modified FET, and the response to EBOV was measured as a function of the shift of Dirac voltage. The method can detect the EBOV over the concentration range from 2.4 × 10-12 g·mL-1 to 1.2 × 10-7 g·mL-1 and with a limit of detection as low as 2.4 pg·mL-1. The assay has satisfactory specificity and was applied to the quantitation of inactivated EBOV in spiked serum. Graphical abstract Schematic presentation of the field effect transistor (FET) modified with reduced graphene oxide (RGO) for Ebola Virus (EBOV) detection. Specific binding between EBOV and the anti-EBOV antibody (Ab) on the FET device leads to obvious current change.

Effect of application of herbal medicine paste to "Tianshu" (ST25)on intestinal mobility and expression of vasoactive intestinal peptide and substance P in colonic myenteric plexus in rats with functional constipation / 针刺研究

OBJECTIVE: To observe the effect of acupoint application at bilateral "Tianshu" (ST25) on intestinal mobility and immunoactivity of vasoactive intestinal peptide (VIP) and substance P (SP) in colonic myenteric plexus of rats with functional constipation (FC), so as to analyze its mechanisms underlying improving FC. METHODS: Forty male SD rats were randomly divided into 4 groups, namely normal control, model, acupoint application and medication, with 10 rats in each group. The FC model was established by gavage of Loperamide Hydrochloride suspension fluid (0.5 mg/mL, 3 mg·kg-1·d-1) for 7 days. Herbal medicine paste (composed of Rheum Officinale, Sodium Sulfate, Mangnolia Officinalis, etc.) was applied to bilateral ST25 for 6 h, once daily for 4 weeks. Rats of the medication group were treated by gavage of Mosapride suspension fluid (0.15 mg/mL, 1.58 mg·kg-1·d-1) for 4 weeks. After the treatment, the rats were deprived of water for 12 hours, and then treated by gavage of 2 mL of activated carbon suspension, followed by recording the first black defecation time and the number of fecal particles and water content of feces within 6 h so as to assess the intestinal mobility. The immunoactivity and average surface density of VIP and SP positive granules in the colonic myenteric plexus were detected by immunohistochemistry. RESULTS: Compared with the normal control group, the first black defecation time was significantly prolonged, and the number and water content of fecal particles within 6 h, and the expression and the average surface density of VIP and SP were significantly reduced in the model group (P0.05). CONCLUSION: Acupoint application may improve the intestinal motility in FC rats, which may be asso-ciated with its effects in up-regulating the immunoactivity of VIP and SP in colonic myenteric plexus of the large intestine.

Molybdenum disulfide field-effect transistor biosensor for ultrasensitive detection of DNA by employing morpholino as probe.

This work reports on a molybdenum disulfide (MoS2) based field-effect transistor (FET) biosensor for ultrasensitive label-free detection of DNA via phosphorodiamidate morpholino oligos (PMO)-DNA hybridization. After the chip was fabricated and the sensing channel was modified with positive charges, the negatively charged MoS2 nanosheet was drop-casted onto the channel, enabling MoS2 to tightly bind to the sensing surface via electrostatic interactions. Meanwhile, DNA analogue, PMO, was immobilized on the MoS2 surface, and detection of PMO-DNA hybridization was conducted by the fabricated MoS2 FET biosensor. Due to the neutral character and high affinity of PMO, a limit of detection (LOD) down to 6 fM was obtained, which is lower than that of the previously reported MoS2 FET DNA biosensor based on DNA-DNA hybridization. In addition, the MoS2 FET biosensor also showed high sequence specificity capable of distinguishing the complementary DNA from one-base mismatched DNA, three-base mismatched DNA and noncomplementary DNA. Moreover, the unique FET biosensor was able to detect DNA in complex sample like serum, making the method potential in disease diagnostics.

Post-treatment with Ma-Huang-Tang ameliorates cold-warm-cycles induced rat lung injury.

Frequent and drastic ambient temperature variation may cause respiratory diseases such as common cold and pneumonia, the mechanism for which is not fully understood, however, due to lack of appropriate animal models. Ma-Huang-Tang (MHT) is widely used in China for treatment of respiratory diseases. The present study aimed to investigate the effect of MHT on temperature alternation induced rat lung injury and explore underlying mechanisms. Male Sprague-Dawley rats were exposed to a cold environment for 1 h and then shifted to a warm environment for 30 min. This cold and warm alteration cycled 4 times. Rats were administrated with MHT (1.87 g/kg) by gavage 6 h after cold-warm-cycles. Cold-warm-cycles induced pulmonary microcirculatory disorders, lung edema and injury, decrease in the expression of tight junction proteins, increase in VE-cadherin activation, increase in the expression and activation of Caveolin-1, Src and NF-κB, and NADPH oxidase subunits p47phox, p40phox and p67phox membrane translocation and inflammatory cytokines production. All alterations were significantly ameliorated by post-treatment with MHT. This study showed that rats subjected to cold-warm-cycles may be used as an animal model to investigate ambient temperature variation-induced lung injury, and suggested MHT as a potential strategy to combat lung injury induced by temperature variation.

Detection of heart failure-related biomarker in whole blood with graphene field effect transistor biosensor.

Since brain natriuretic peptide (BNP) has become internationally recognized biomarkers in the diagnosis and prognosis of heart failure (HF), it is highly desirable to search for a novel sensing tool for detecting the patient's BNP level at the early stage. Here we report a platinum nanoparticles (PtNPs)-decorated reduced graphene oxide (rGO) field effect transistor (FET) biosensor coupled with a microfilter system for label-free and highly sensitive detection of BNP in whole blood. The PtNPs-decorated rGO FET sensor was obtained by drop-casting rGO onto the pre-fabricated FET chip and subsequently assembling PtNPs on the graphene surface. After anti-BNP was bound to the PtNPs surface, BNP was successfully detected by the anti-BNP immobilized FET biosensor. It was found that the developed FET biosensor was able to achieve a low detection limitation of 100fM. Moreover, BNP was successfully detected in human whole blood sample treated by a custom-made microfilter, suggesting the sensor's capability of working in a complex sample matrix. The developed FET biosensor provides a new sensing platform for protein detection, showing its potential applications in clinic sample.

Real-Time Monitoring of Nitric Oxide at Single-Cell Level with Porphyrin-Functionalized Graphene Field-Effect Transistor Biosensor.

An ultrasensitive and highly efficient assay for real-time monitoring of nitric oxide (NO) at single-cell level based on a reduced graphene oxide (RGO) and iron-porphyrin-functionalized graphene (FGPCs) field-effect transistor (FET) biosensor is reported. A layer-to-layer assembly of RGO and FGPCs on a prefabricated FET sensor surface through π-π stacking interaction allowed superior electrical conductivity caused by RGO, and highly catalytic specificity induced by metalloporphyrin, ensuring the ultrasensitive and highly specific detection of NO. The results demonstrated that the RGO/FGPCs FET biosensor was capable of real-time monitoring of NO in the range from 1 pM to 100 nM with the limit of detection as low as 1 pM in phosphate-buffered saline (PBS) and 10 pM in the cell medium, respectively. Moreover, the developed biosensor could be used for real-time monitoring of NO released from human umbilical vein endothelial cells (HUVECs) at single-cell level. Along with its miniaturized sizes, ultrasensitive characteristics, and fast response, the FET biosensor is promising as a new platform for potential biological and diagnostic applications.

Posttreatment with Ma-Xing-Shi-Gan-Tang, a Chinese medicine formula, ameliorates lipopolysaccharide-induced lung microvessel hyperpermeability and inflammatory reaction in rat.

OBJECTIVE: The aim of present study was to investigate the efficacy of MXSGT, a traditional Chinese medicine formula used for treatment of respiratory system diseases, in the LPS-induced rat ALI particularly with a focus on its effect on lung microvascular hyperpermeability and inflammatory reaction. METHODS: Male Sprague-Dawley rats were injected with LPS (7.5 mg/kg, 1.5 mg/mL) intraperitoneally. MXSGT (0.52 g or 2.61 g/kg) was given by gavage six hours after LPS injection. RESULTS: LPS stimulation resulted in a reduced survival rate, deteriorated vital signs, an increase in the number of leukocytes adhering to lung venules, the albumin leakage, the activity of MPO in lung tissues, the production of pro-inflammatory cytokines and lung perivascular edema. After LPS stimulation, western blot analysis revealed an increase in the expression of ICAM-1 and toll-like receptor 4, a decrease in tight junction proteins and an activation of cav-1, Src, and NF-κB. All the LPS-induced alterations were significantly attenuated by posttreatment with MXSGT. CONCLUSIONS: This study demonstrated MXSGT as a potential strategy for lung microvascular hyperpermeability and inflammatory reaction in ALI, and suggested that the beneficial role of MXSGT was correlated with toll-like receptor 4, Src, and NF-κB.