Optimizing event-based neural networks on digital neuromorphic architecture: a comprehensive design space exploration.

Neuromorphic processors promise low-latency and energy-efficient processing by adopting novel brain-inspired design methodologies. Yet, current neuromorphic solutions still struggle to rival conventional deep learning accelerators' performance and area efficiency in practical applications. Event-driven data-flow processing and near/in-memory computing are the two dominant design trends of neuromorphic processors. However, there remain challenges in reducing the overhead of event-driven processing and increasing the mapping efficiency of near/in-memory computing, which directly impacts the performance and area efficiency. In this work, we discuss these challenges and present our exploration of optimizing event-based neural network inference on SENECA, a scalable and flexible neuromorphic architecture. To address the overhead of event-driven processing, we perform comprehensive design space exploration and propose spike-grouping to reduce the total energy and latency. Furthermore, we introduce the event-driven depth-first convolution to increase area efficiency and latency in convolutional neural networks (CNNs) on the neuromorphic processor. We benchmarked our optimized solution on keyword spotting, sensor fusion, digit recognition and high resolution object detection tasks. Compared with other state-of-the-art large-scale neuromorphic processors, our proposed optimizations result in a 6× to 300× improvement in energy efficiency, a 3× to 15× improvement in latency, and a 3× to 100× improvement in area efficiency. Our optimizations for event-based neural networks can be potentially generalized to a wide range of event-based neuromorphic processors.

Novel hemoperfusion adsorbents based on collagen for efficient bilirubin removal - A thought from yellow skin of patients with hyperbilirubinemia.

Hemoperfusion is a well-developed method for removing bilirubin from patients with hyperbilirubinemia. The performance of adsorbents is crucial during the process. However, most adsorbents used for bilirubin removal are not suitable for clinical applications, because they either have poor adsorption performance or limited biocompatibility. Patients with hyperbilirubinemia usually have distinctive yellow skin, indicating that collagen, a primary component of the skin, may be an effective material for absorbing bilirubin from the blood. Based on this idea, we designed and synthesized collagen (Col) and collagen-polyethyleneimine (Col-PEI) microspheres and employed them as hemoperfusion adsorbents for bilirubin removal. The microspheres have an efficient adsorption rate, higher bilirubin adsorption capacity, and competitive adsorption of bilirubin in the bilirubin/bovine serum albumin (BSA) solution. The maximum adsorption capacities of Col and Col-PEI microspheres for bilirubin are 150.2 mg/g and 258.4 mg/g, respectively, which are higher than those of most traditional polymer microspheres. Additionally, the microspheres exhibit excellent blood compatibility originating from collagen. Our study provides a new collagen-based strategy for the hemoperfusion treatment of hyperbilirubinemia.

A novel recyclable hemoperfusion adsorbent based on TiO2 nanotube arrays for the selective removal of ß2-microglobulin.

Prolonged and excessive accumulation of ß2-microglobulin (ß2m) in the blood can lead to various kidney-related and other diseases. Currently, the most effective method of removing ß2m from the blood is hemoperfusion. Although some traditional hemoperfusion adsorbents such as cellulose and polystyrene microspheres have been used for the removal of ß2m, their selectivity still needs improvement. Immunosorbents have been developed to address this issue, but high cost and limited application are concerns. TiO2 nanotube arrays (TNTAs) have shown great potential in adsorption-related biomedical applications. In this study, we designed and developed a novel TNTA-based hemoperfusion adsorbent for the removal of ß2m, which has demonstrated good biocompatibility, selectivity, and reusability. We investigated the ß2m adsorption capacities of TNTAs with different pore sizes. The results indicate that TNTAs with a pore size matching the size of ß2m exhibit higher adsorption capacity while also having lower adsorption capacity for albumin, showing the importance of pore size on the selectivity of adsorbents. Additionally, green regeneration of TNTAs is achieved via the photocatalytic activity originating from TiO2. Even after five cycles, the adsorption capacity of TNTAs remained above 70%. Our work demonstrates that inorganic materials with ordered pores are capable to be candidates for hemoperfusion, possessing advantages over traditional organic materials such as high stability, security, and low cost.

A Multifunctional Nanocarrier System for Highly Efficient and Targeted Delivery of Ketamine to NMDAR Sites for Improved Treatment of Depression.

Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)-ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC-RM@HA-MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA-loaded NPs (AC-RM@HA-MS-KA) are constructed with a multilayer core-shell structure. KA-loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC-membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang-2-Con-G, AC) to achieve specific targeting. One peptide (Ang-2) is acted as a guide to facilitate the crossing of the blood-brain barrier (BBB), while the other (Con-G) is functioned as a ligand for the targeted delivery of KA to the N-methyl-D-aspartate receptor sites. Animal experiments reveal that AC-RM@HA-MS-KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.

Genetic engineering of bacteriophages: Key concepts, strategies, and applications.

Bacteriophages are the most abundant biological entity in the world and hold a tremendous amount of unexplored genetic information. Since their discovery, phages have drawn a great deal of attention from researchers despite their small size. The development of advanced strategies to modify their genomes and produce engineered phages with desired traits has opened new avenues for their applications. This review presents advanced strategies for developing engineered phages and their potential antibacterial applications in phage therapy, disruption of biofilm, delivery of antimicrobials, use of endolysin as an antibacterial agent, and altering the phage host range. Similarly, engineered phages find applications in eukaryotes as a shuttle for delivering genes and drugs to the targeted cells, and are used in the development of vaccines and facilitating tissue engineering. The use of phage display-based specific peptides for vaccine development, diagnostic tools, and targeted drug delivery is also discussed in this review. The engineered phage-mediated industrial food processing and biocontrol, advanced wastewater treatment, phage-based nano-medicines, and their use as a bio-recognition element for the detection of bacterial pathogens are also part of this review. The genetic engineering approaches hold great potential to accelerate translational phages and research. Overall, this review provides a deep understanding of the ingenious knowledge of phage engineering to move them beyond their innate ability for potential applications.

Colorimetric platform based on synergistic effect between bacteriophage and AuPt nanozyme for determination of Yersinia pseudotuberculosis.

The development of a novel colorimetric method is reported, using vB_YepM_ZN18 phages along with AuPt nanozyme for the sensitive detection of Y. pseudotuberculosis. The phage used in this work has been extracted from hospital sewer water and is highly specific toward Y. pseudotuberculosis. The synthesized AuPt NPs possess peroxidase-like activity, which is suitable in the development of nanozyme based detection system. Furthermore, phages@MB and AuPt@phages are added into the bacterial samples for co-incubation, forming an intercalated complex. The magnetic separation and absorbance analysis of enzymatic reaction are carried out for the detection of targeted bacteria. The proposed method has a limit of detection of 14 CFU/mL, a wide linear range from 2.50 × 101 ~ 2.50 × 107 CFU/mL and the assay completion time is 40 min. Benefitting from the outperformance of this sensor, we have successfully employed the developed sensing platform for the detection of Y. pseudotuberculosis in food industry and hospital specimens.

Progressive interstitial lung disease in hypomyopathic dermatomyositis in the COVID-19 pandemic: A case report.

BACKGROUND: Clinically amyopathic dermatomyositis (CADM) is characterized by typical skin lesions with no (amyopathic) or subclinical (hypomyopathic) evidence of muscle involvement. Patients with CADM may also develop rapidly progressive interstitial lung disease (ILD), and have a poor prognosis. However, the diagnosis of rapidly progressive ILD faces a challenge during the severe acute respiratory syndrome coronavirus 2 pandemic. Severe acute respiratory syndrome and ground-glass attenuation on a chest computed tomography scan are the presenting features in both conditions. CASE PRESENTATION: A 45-year-old woman with amyopathic dermatomyositis had acute onset of fever and dyspnea in February 2020. She had abnormal lung findings on CT scan. Polymerase chain reaction testing for SARS-CoV-2 was not available at that time. Chest CT revealed non-specific manifestations that could be either the signs of ILD or SARS-CoV-2 infection. Antiviral therapy was initiated with oseltamivir. Three days later, she had erythema on face, palm, and back. The ratio of lactate dehydrogenase (LDH) isoenzyme 3 to total LDH was elevated. The ratio of LDH isoenzyme 1 to total LDH was declined. Therefore, she was transferred to the rheumatology ward for further treatment. However, she died from respiratory failure 2 weeks later. CONCLUSIONS: We speculate that the altered LDH isoenzyme pattern may be an early biomarker for co-occurrence of CADM and ILD.

Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome.

Small molecules encoded by biosynthetic pathways mediate cross-species interactions and harbor untapped potential, which has provided valuable compounds for medicine and biotechnology. Since studying biosynthetic gene clusters in their native context is often difficult, alternative efforts rely on heterologous expression, which is limited by host-specific metabolic capacity and regulation. Here, we describe a computational-experimental technology to redesign genes and their regulatory regions with hybrid elements for cross-species expression in Gram-negative and -positive bacteria and eukaryotes, decoupling biosynthetic capacity from host-range constraints to activate silenced pathways. These synthetic genetic elements enabled the discovery of a class of microbiome-derived nucleotide metabolites-tyrocitabines-from Lactobacillus iners. Tyrocitabines feature a remarkable orthoester-phosphate, inhibit translational activity, and invoke unexpected biosynthetic machinery, including a class of "Amadori synthases" and "abortive" tRNA synthetases. Our approach establishes a general strategy for the redesign, expression, mobilization, and characterization of genetic elements in diverse organisms and communities.

Small proline-rich protein 1A promotes lung adenocarcinoma progression and indicates unfavorable clinical outcomes.

Small proline-rich protein 1A (SPRR1A) plays a critical role in regulating squamous cell differentiation. SPRR1A overexpression was reported to be closely related to the progression of some tumors, such as gastric cancer and colon cancer. However, the function of SPRR1A in lung adenocarcinoma (LUAD) has not been elucidated. Here, we first examined the expression pattern of SPRR1A in LUAD tissues, which indicated that the SPRR1A expression level was significantly elevated in LUAD tissues compared with normal lung tissues. High expression of SPRR1A was closely related to larger tumor size. LUAD patients with higher SPRR1A expression had poorer overall survival and SPRR1A was identified as an independent unfavorable prognosis factor. In addition, the effects of SPRR1A on lung cancer cells were tested through cellular experiments and the result demonstrated that knockdown of SPRR1A can suppress the proliferation and invasion capacities of tumor cells, while overexpressing SPRR1A exerted opposite effects. Finally, our findings were substantiated by the data obtained from in vivo xenografts using a mice model. In conclusion, LUAD patients with higher SPRR1A expression were more predisposed to poorer clinical outcomes and unfavorable prognoses, indicating the potential role of SPRR1A as a novel clinical biomarker and therapeutic target.

Boosting the Electrochemical Performance of PI-5-CA/C-SWCNT Nanohybrid for Sensitive Detection of E. coli O157:H7 From the Real Sample.

Redox activity is an important indicator for evaluating electrochemical biosensors. In this work, we have successfully polymerized indole-5-carboxylic acid into poly-5-carboxyindole nanomaterials (PI-5-CA), using its superior redox activity, and introduced carboxylated single-walled carbon nanotubes (C-SWCNTs) to synthesize a composite material. Finally, a synthesized composite material was used for the modification of the glass carbon electrode to fabricate the PI-5-CA/C-SWCNTs/GCE-based immunosensor and was successfully applied for the sensitive detection of E. coli O157:H7. The fabricated immunosensor exhibited an outstanding electrocatalytic activity toward the detection of E. coli O157:H7 with a remarkably lowest limit of detection (2.5 CFU/ml, LOD = 3 SD/k, n = 3) and has a wide linear range from 2.98×101 to 2.98×107 CFU/ml. Inspired from the excellent results, the fabricated electrode was applied for the detection of bacteria from real samples (water samples) with a good recovery rate (98.13-107.69%) as well as an excellent stability and specificity. Owing to its simple preparation, excellent performance, and detection time within 30 min, our proposed immunosensor will open a new horizon in different fields for the sensitive detection of bacteria from real samples.

Boosting electrocatalytic activity of carbon fiber@fusiform-like copper-nickel LDHs: Sensing of nitrate as biomarker for NOB detection.

Morphological evolution of layered double hydroxides (LDHs) with preferential crystal facets has appealed gigantic attention of research community. Herein, we prepare hierarchical hybrid material by structurally integrating fusiform-like CuNiAl LDHs petals on conductive backbone of CF (CF@CuNiAl LDHs) and investigate electrocatalytic behavior in nitrate reduction over a potential window of -0.7 V to +0.7 V. The CF@CuNiAl LDHs electrode exhibits remarkable electrocatalytic aptitude in nitrate sensing including broad linear ranges of 5 nM to 40 µM and 75 µM to 2.4 mM with lowest detection limit of 0.02 nM (S/N = 3). The sensor shows sensitivity of 830.5 ±â€¯1.84 µA mM1- cm2- and response time within 3 s. Owing to synergistic collaboration of improved electron transfer kinetics, specific fusiform-like morphology, presence of more catalytically active {111} facets and superb catalytic activity of LDHs, CF@CuNiAl LDHs electrode has outperformed as electrochemical sensor. Encouraged from incredible performance, CF@CuNiAl LDHs flexible electrode has been applied in real-time in-vitro detection of nitrite oxidizing bacteria (NOB) through the sensing of nitrate because NOB convert nitrite into nitrate by characteristic metabolic process to obtain their energy. Further, CF@CuNiAl LDHs based sensing podium has also been employed in in-vitro detection of nitrates from mineral water, tap water and Pepsi drink.

Light regulates stomatal development by modulating paracrine signaling from inner tissues.

Developmental outcomes are shaped by the interplay between intrinsic and external factors. The production of stomata-essential pores for gas exchange in plants-is extremely plastic and offers an excellent system to study this interplay at the cell lineage level. For plants, light is a key external cue, and it promotes stomatal development and the accumulation of the master stomatal regulator SPEECHLESS (SPCH). However, how light signals are relayed to influence SPCH remains unknown. Here, we show that the light-regulated transcription factor ELONGATED HYPOCOTYL 5 (HY5), a critical regulator for photomorphogenic growth, is present in inner mesophyll cells and directly binds and activates STOMAGEN. STOMAGEN, the mesophyll-derived secreted peptide, in turn stabilizes SPCH in the epidermis, leading to enhanced stomatal production. Our work identifies a molecular link between light signaling and stomatal development that spans two tissue layers and highlights how an environmental signaling factor may coordinate growth across tissue types.

Poly(indole-5-carboxylic acid)/reduced graphene oxide/gold nanoparticles/phage-based electrochemical biosensor for highly specific detection of Yersinia pseudotuberculosis.

Yersinia pseudotuberculosis is an enteric bacterium causing yersiniosis in humans. The existing Yersinia pseudotuberculosis detection methods are time-consuming, requiring a sample pretreatment step, and are unable to discriminate live/dead cells. The current work reports a phage-based electrochemical biosensor for rapid and specific detection of Yersinia pseudotuberculosis. The conductive poly(indole-5-carboxylic acid), reduced graphene oxide, and gold nanoparticles are applied for surface modification of the electrode. They possess ultra-high redox stability and retain 97.7% of current response after performing 50 consecutive cycles of cyclic voltammetry.The specific bacteriophages vB_YepM_ZN18 we isolated from hospital sewage water were immobilized on modified electrodes by Au-NH2 bond between gold nanoparticles and phages. The biosensor fabricated with nanomaterials and phages were utilized to detect Yersinia pseudotuberculosis successfully with detection range of 5.30 × 102 to 1.05 × 107 CFU mL-1, detection limit of 3 CFU mL-1, and assay time of 35 min. Moreover, the biosensor can specifically detect live Yersinia pseudotuberculosis without responding to phage-non-host bacteria and dead Yersinia pseudotuberculosis cells. These results suggest that the proposed biosensor is a promising tool for the rapid and selective detection of Yersinia pseudotuberculosis in food, water, and clinical samples.

Bacteriophage-based advanced bacterial detection: Concept, mechanisms, and applications.

Some bacterial species are deadly disease-causing pathogens with high morbidity and mortality in humans worldwide. Key interfaces in the transmission of bacterial pathogens include food, water, dairy products, peridomestic animals, and human interplay. Early-stage detection of such bacteria is crucial in minimizing the risk of bacterial diseases and ensuring early diagnosis. Majority of the conventional microbiological and biochemical detection methods are laborious, require skilled individuals, and are not always accurate. Various molecular diagnostic tools and assays, utilizing sensitive and specific biorecognition elements, such as enzymes, antibodies, and nucleic acids, have been developed and widely used for the detection of pathogenic bacteria. An ideal biorecognition element for the detection of pathogens should be highly specific, stable, sensitive, selective, rapid, easily available, and cost-effective. Bacteriophages, which meet such prerequisites, may be used as biorecognition element alternatives to the currently available molecular probes in the development of cost-effective, specific, quick, sensitive, and reliable platforms (sensors and assays) for the detection of bacterial pathogens. This review details bacteriophage biology and various recognition sites and receptor-binding proteins on the surfaces of tailed phages, which can be used as the recognition sites for specific bacterial detection. It highlights structures and receptors on the surface of bacteria for binding and attachment of specific phages. These features of bacteria and phages provide a basis for establishing methodologies for phage-based bacterial detection, including phage-induced bacterial lysis, phages immobilized on a transducer surface, fluorescently labelled phages, phage-conjugated quantum dots, and recombinant reporter phages, particularly monitored through optical and electrochemical transducer systems.

Trends in biosensing platforms for SARS-CoV-2 detection: A critical appraisal against standard detection tools.

In this ongoing theme of coronavirus disease 2019 (COVID-19) pandemic, highly sensitive analytical testing platforms are extremely necessary to detect SARS-CoV-2 RNA and antiviral antibodies. To limit the viral spread, prompt and precise diagnosis is crucial to facilitate treatment and ensure effective isolation. Accurate detection of antibodies (IgG and IgM) is imperative to understand the prevalence of SARS-CoV-2 in public and to inspect the proportion of immune individuals. In this review, we demonstrate and evaluate some tests that have been used commonly to detect SARS-CoV-2. These include nucleic acid and serological tests for the detection of SARS-CoV-2 RNA and specific antibodies in infected people. Moreover, the vitality of biosensing technologies emphasizing on optical and electrochemical biosensors toward the detection of SARS-CoV-2 has also been discussed here. The early diagnosis of COVID-19 based on detection of reactive oxygen species overproduction because of virus-induced dysfunctioning of lung cells has also been highlighted.

COVID-19 Impacts, Diagnosis and Possible Therapeutic Techniques: A Comprehensive Review.

BACKGROUND: The spread of COVID-19 has become a growing cause of mortalities over the globe since its major outbreak in December 2019. The scientific and medical communities are rallying to study different strains and probable mutations to develop more rapid and reliable molecular diagnostic tests and possible therapeutic approaches for SARS-CoV-2. INTRODUCTION: In the first section, following the introductory part, we shed light on structural and pathogenic features of SARS-CoV-2 and risk factors related to age, gender, neonatal and comorbidities. The next section summarizes the current diagnostic tests for COVID-19, such as nucleic acid and computed tomography (CT) techniques, with further emphasis on emerging diagnostic approaches for COVID-19. METHODS: Further, we also review the ongoing therapeutic practices which can block virus-host interaction, cease viral proliferation or inhibit hyperbolic host immune response with subsections on drug therapy, cell therapy, immunotherapy and herbal medicines that are being used for the possible treatment of patients. RESULTS AND CONCLUSION: Among the different promising drugs, remdesivir, by inhibiting the RNA-dependent RNA-Polymerase activity, gives much better results, including declined viral load and quick lung tissue recovery. The long-lasting repercussions of COVID-19 have also been discussed at the end. In this review, we have also critically discussed the progress in several vaccines that are under development.

Combined exposure to formaldehyde and PM2.5: Hematopoietic toxicity and molecular mechanism in mice.

PM2.5 and formaldehyde (FA) are major outdoor and indoor air pollutants in China, respectively, and both are known to be harmful to human health and to be carcinogenic. Of all the known chronic health effects, leukaemia is one of the most serious health risks associated with these two pollutants. To explore the influence and underlying mechanisms of exposure to formaldehyde and PM2.5 on hematopoietic toxicity, we systematically studied the toxicity induced in hematopoietic organs: bone marrow (BM); spleen; and myeloid progenitor cells (MPCs). Male Balb/c mice were exposed to: PM2.5 (20, 160 µg/kg·d) at a dose of 40 µL per mouse or formaldehyde (0.5, 3.0 mg/m3) for 8 h per day for 2 weeks or co-exposed to formaldehyde and PM2.5 (20 µg/kg·d PM2.5 + 0.5 mg/m3 FA, 20 µg/kg·d PM2.5 + 3 mg/m3 FA, 160 µg/kg·d PM2.5 + 0.5 mg/m3 FA, 160 µg/kg·d PM2.5 + 3 mg/m3 FA) for 2 weeks. Similar toxic effects were found in the formaldehyde-only and PM2.5-only groups, including significant decrease of blood cells and MPCs, along with decreased expression of hematopoietic growth factors. In addition, individual exposure of formaldehyde or PM2.5 increased oxidative stress, DNA damage and immune system disorder by destroying the balance of Th1/Th2, and Treg/Th17. DNA repair was markedly inhibited by deregulating the mammalian target of rapamycin (mTOR) pathway. Combined exposure to PM2.5 and formaldehyde led to more severe effects. Administration of Vitamin E (VE) was shown to attenuate these effects. In conclusion, our findings suggested that PM2.5 and formaldehyde may induce hematopoietic toxicity by reducing the expression of hematopoietic growth factors, increasing oxidative stress and DNA damage, activating the 'immune imbalance' pathway and suppressing the DNA-repair related mTOR pathway. The hematopoietic toxicity induced by combined exposure of PM2.5 and formaldehyde might provide further insights into the increased incidence of hematological diseases, including human myeloid leukaemia.

High-density phage particles immobilization in surface-modified bacterial cellulose for ultra-sensitive and selective electrochemical detection of Staphylococcus aureus.

The routinely used enzymes, antibodies, and nucleic acids-based biosensors for detection of Staphylococcus aureus are often overwhelmed by limited selectivity, sensitivity, high cost, and inability to discriminate between live/dead cells. This necessitates the development of an ultra-sensitive, stable, and selective electrochemical biosensor capable of discriminating live S. aureus in a mixture of live/dead cells in food samples. The current study reports the development of an electrochemical biosensor through the immobilization of bacteriophage in surface-modified bacterial cellulose (BC) matrix. BC being highly porous and fibrous, offers a high surface area for the impregnation of carboxylated multiwalled carbon nanotubes (c-MWCNTs) and allows high-density phage immobilization. Surface modification of BC/c-MWCNTs with polyethyleneimine (PEI) provides a positive charge that facilitates oriented phage immobilization. FE-SEM and FT-IR analyses confirmed the development of BC/c-MWCNTs-PEI-phage bio-interface. Confocal microscopy analysis showed 11.7 ± 1.2 phage particles⋅µm-2 immobilized in the BC matrix and showed anti-staphylococcal activity by producing clear lytic zone and reduced bacterial growth. Differential pulse voltammetry (DPV) analysis detected 3 CFU⋅mL-1 and 5 CFU⋅mL-1 of S. aureus in phosphate buffer saline (PBS) and milk, respectively, within 30 min at neutral pH and showed stability over 6-weeks at 4 °C. The biosensor showed high specificity for S. aureus, both in pure and mixed cultures of non-host bacteria, and effectively discriminated live S. aureus in a mixture of live/dead cells. The developed biosensor represents a simple, sensitive, specific, and accurate tool for early detection of S. aureus in food samples.

A highly sensitive label-free electrochemical immunosensor based on poly(indole-5-carboxylicacid) with ultra-high redox stability.

The high stability of redox signal is one of the most crucial factors in construction of electrochemical immunosensors. However, the redox-active species usually show low stability and poor conductivity, which inhibits their application in electrochemical immunosensors. In this work, we report that the conductive polymer poly(indole-5-carboxylic acid) (PIn-5-COOH) possesses ultra-high redox stability. The redox signal of PIn-5-COOH could remain 96.03% after 500 cyclic voltammery (CV) cycles in buffer solution with pH of 6.2, while the redox signals in most of the previous reports only remained less than 90% after 50 CV cycles. Our mechanism investigation indicated that the ultra-high redox stability of PIn-5-COOH should be attributed to its stable structure. The electrochemical immunosensors fabricated with PIn-5-COOH/MWCNTs-COOH nanocomposite showed a wide linear range from 0.001 ng mL-1 to 100 ng mL-1 and a low detection limit of 0.33 pg mL-1 for the detection of alpha fetoprotein. This study opens up a new avenue for the construction of electrochemical immunosensors with ultra-stable redox signal.

MiR-124 regulates transforming growth factor-ß1 induced differentiation of lung resident mesenchymal stem cells to myofibroblast by repressing Wnt/ß-catenin signaling.

Lung resident mesenchymal stem cells (LR-MSCs) contribute to the progression of idiopathic pulmonary fibrosis (IPF). We aimed to investigate the molecular mechanism underlying LR-MSCs regulation upon transforming growth factor (TGF)-ß1 stimulation. We induced fibrogenic differentiation of LR-MSCs isolated from mice by TGF-ß1. Several stem cell markers were detected by flow cytometric analysis. Protein expression level was tested by Western blotting and mRNA level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, proliferation and apoptosis were measured. TGF-ß1 promoted fibrogenic differentiation of LR-MSCs and upregulated ß-catenin and p-glycogen synthase kinase-3ß, suggesting the activation of Wnt signaling. MicroRNA (MiR)-124-3p was significantly upregulated in TGF-ß1 treated LR-MSCs compared to untreated cells. Intriguingly, silence of miR-124 reversed the TGF-ß1-induced changes in cell viability and proliferation, and also led to a decrease of cell apoptosis. Additionally, in miR-124 silenced cells, α-smooth muscle actin, collagen I and fibronectin were downregulated compared to control cells. We ultimately identified a new target of miR-124, AXIN1, which was repressed by miR-124. In conclusion, miR-124 regulates AXIN1 to activate Wnt signaling and therefore plays a crucial role in the TGF-ß1-induced fibrogenic differentiation.