A simple fluorescence detection of acetylcholinesterase with peroxidase-like catalysis from iodide.

Acetylcholinesterase (AChE) is an important enzyme in the central and peripheral nervous system that regulates the balance of the neurotransmitter acetylcholine. In this work, a simple, selective and sensitive fluorescence assay was developed toward AChE activity. A conventional AChE substrate acetylthiocholine iodide (ATCI) was applied. Instead directly rendering a signaling, it was found that free iodide ions was released during the enzymatic hydrolysis of ATCI. These ions further catalyzed the oxidation of non-emissive o-phenylenediamine (OPD) into a fluorescent product. This gave a response differed from frequently-adopted sulfhydryl- -based signals and thus minimized related interferences. All materials included in this process were directly available and no additional syntheses were required. Due to the extra iodide-based catalysis included, this scheme was capable of providing a sensitive response toward AChE in the range of 0.01-8 U/L, with a limit of detection at 0.006 U/L. This method was further extended onto chlorpyrifos as an exemplary AChE inhibitor, with a detection down to 3 pM.

Flash phase engineering of MoS2 nanofilms for enhanced photoelectrochemical performance.

A heterophase structure combining semiconducting 2H- and metallic 1T-MoS2 exhibits significantly enhanced photoelectrochemical performance due to the electrical coupling and synergistic effect between the phases. Therefore, site-selective effective phase engineering is crucial for the fabrication of MoS2-based photoelectrochemical devices. Here, we employed a flash phase engineering (FPE) strategy to precisely fabricate a 2H-1T heterophase structure. This technique allows simple, efficient, and precise control over the micropatterning of MoS2 nanofilms while enabling site-selective phase transition from the 1T to the 2H phase. The detection of reduced glutathione (GSH) showed an approximately 5-fold increase in sensitivity when using the electrode fabricated by FPE.

Development of a P-tau217 Electrochemiluminescent Immunosensor Reinforced with Au-Cu Nanoparticles for Alzheimer's Disease Precaution.

To simply and rapidly detect the highly phosphorylated tau protein at threonine 217 (p-tau217) as a precautionary measure against Alzheimer's disease and distinguish it from other neurodegenerative diseases, a novel immunosensor was prepared using luminol as the electrochemiluminescent (ECL) sensing probe reinforced by Au-Cu nanoparticles (Au-Cu NPs). The Au-Cu alloy NPs were prepared via a co-reduction reaction, exhibiting excellent conductivity and catalytic activity. These properties remarkably enhanced the ECL of luminol, providing a suitable background for the sensing response. After the Au-Cu NPs were decorated on the surface of indium tin oxide glass using 3-amino-propyl trimethoxysilane, the antibody of p-tau217 was immobilized via dominant Au-N bonding to enable the biological specificity of the immunosensor. When p-tau217 specifically interacted with an antibody to form an immune complex on the sensing interface, the ECL signal of the sensor was considerably inhibited by the resulting giant biomolecular complex. This complex prevented luminol diffusion to the electrode surface and electron transfer. The resulting immunosensor showed remarkable sensitivity to p-tau217, with a wide linear detection range from 5 to 600 pg/mL. A detection limit of 0.56 pg/mL was achieved, with recoveries in human serum ranging from 92.3 to 109%. This ECL immunosensor demonstrated high sensitivity and specificity toward p-tau217, along with good reproducibility and stability, providing a new approach for clinical research on Alzheimer's disease.

Simple and sensitive fluorescence detection of trypsin with Cu2+-Bovine serum albumin complex as a peroxidase mimic.

Trypsin is a serine protease playing a key role in regulating pancreatic exocrine function and can be applied as a marker for the diagnosis of pancreatitis. In this work, a convenient and sensitive fluorescent assay was developed toward trypsin. Hydrogen peroxide slowly oxidized a non-fluorescent o-phenylenediamine (OPD) into a fluorescent product 2,3-diaminophenothiazine (DAP) under the catalytic from copper ions. After the introduction of bovine serum albumin (BSA), the combination of BSA with copper ions formed a peroxidase mimic and significantly accelerated the reaction rate. As an efficient protease, trypsin cleaved the lysine and arginine residues in BSA. This destroyed the binding between Cu2+ and BSA, and brought in a reduction of the catalytic effect. The accompanying decrease in fluorescence provided a response to trypsin in the range of 0.01-600 ng/mL, with a detection limit of 0.007 ng/mL. The scheme had a good selectivity and was successfully applied to the detection of real samples.

Herbal medicine and its impact on the gut microbiota in colorectal cancer.

It is well-established that there are trillions of gut microbiota (GM) in the human gut. GM and its metabolites can reportedly cause cancer by causing abnormal immune responses. With the development of sequencing technology and the application of germ-free models in recent years, significant inroads have been achieved in research on GM and microbiota-related metabolites. Accordingly, the role and mechanism of GM in colorectal cancer (CRC) development have been gradually revealed. Traditional Chinese medicine (TCM) represents an important source of natural medicines and herbal products, with huge potential as anti-CRC agents. The potential application of TCM to target gut microbes for the treatment of colorectal cancer represents an exciting area of investigation.

Novel Electrochemiluminescent Immunosensor Using Dual Amplified Signals from a CoFe Prussian Blue Analogue and Au Nanoparticle for the Detection of Lp-PLA2.

Coronary heart disease (CHD) poses an important threat to human health, and its pathogenesis is the formation of atheromatous plaques in coronary ventricles. Compared to other biomarkers, lipoprotein-associated phospholipase A2 (Lp-PLA2), which is involved in multiple processes of atherosclerosis, is a noticeable inflammatory biomarker related to CHD. Herein, using a multifunctional nanocomposite containing a CoFe Prussian blue analogue (PBA) and Au nanoparticles (AuNPs) (AuNPs@CoFe PBA) as a sensing substrate, an electrochemiluminescent (ECL) immunosensor was developed for the highly sensitive detection of Lp-PLA2. Benefiting from the synergistic effect of the PBA and AuNPs, the nanocomposite exhibits excellent peroxidase-like activity and can catalyze the luminol-ECL reaction, amplifying the ECL signal by ∼29-fold. Meanwhile, the enlarged specific surface area of the nanocomposite and the presence of abundant AuNPs allow the immobilization of more antibody proteins, thereby improving the sensing response of the immunosensor. When the target Lp-PLA2 is captured by the antibody on the sensor surface, the sensor emits a reduced ECL signal because of the increased mass and electron transfer resistance due to the formation of the immune complex. Under optimized conditions, the constructed ECL immunosensor exhibits a broad linear range from 1 to 2200 ng/mL and a low detection limit of 0.21 ng/mL. Additionally, the ECL immunosensor exhibits high specificity, stability, and reproducibility. This work provides a new approach to diagnose CHD and broadened the application of the PBA in the field of ECL sensors.

Assembled Photonic Crystal/Gold Nanoparticle Interface: A Dual Amplifying Electrochemiluminescent Aptasensor for the Ultrasensitive Detection of an Amyloid-ß Monomer.

Amyloid-ß (Aß) protein is considered to be a key biomarker that is closely associated with Alzheimer's disease (AD). The level of Aß, particularly its subtle fluctuation, indicates early neuropathological changes, which poses a considerable challenge in predicting AD, considering the detection limit of sensing technologies. Herein, a new label-free sensor based on luminol electrochemiluminescence (ECL) was proposed by developing a close-packed monolayered-SiO2 array with gold (Au) nanoparticles (NPs) entrapped in their gaps as the basal electrode. The well-organized SiO2 NPs with a quasiphotonic crystal structure amplified the ECL signal via light scattering, while Au NPs amplified the signal by directly catalyzing luminol oxidation. Owing to the dual signal amplification, the proposed electrode furnished an ∼64-fold-intensified ECL signal of luminol as the sensing background. Further, the as-prepared ECL electrode served as the substrate to develop an aptasensor for the sensitive detection of Aß. The inhibition of the ECL signal due to the suppressed diffusion of luminol to the sensor surface acts as an indicator to quantify the amount of Aß. The transfer dynamics mechanism provides a label-free sensing strategy and facilitates the high sensitivity of the aptasensor for Aß detection. Under optimal conditions, the developed aptasensor exhibits an ultrasensitive performance for Aß with a very low limit of detection of 5 fM, providing a new prospect for clinical research on Aß and a promising approach in the field of ECL sensing.

Fluorescence/electrochemiluminescence approach for instant detection of glycated hemoglobin index.

The percentage of glycated hemoglobin (HbA1c) in total hemoglobin (Hb) is an important index for the diagnosis of Type II diabetes (T2D) because it reflects the long-term glucose level in blood. Herein, employing a one-pot co-reduction approach using glutathione (GSH) as structure-directing agent, a cluster-like AuAg nanoparticle (AuAg NPs) material was synthesized, therefore an electrochemiluminescence (ECL) aptamer-sensor for HbA1c detection was developed based on functionalized electrode with this material. Meanwhile, the quantitative determination of total Hb was realized based on the quenching effect of Hb on the fluorescence (FL) of luminol. Under compatible conditions, the results of both indexes can be satisfactorily acquired. This multimodal detection system has a good linear response toward Hb from 0.1 to 2.5 µM and HbA1c from 0.005 to 0.5 µM. The blood test proves this strategy is capable of accurate Hb and HbA1c detection, thus to obtain the percentage of HbA1c in total Hb (HbA1c%), which has the potential application for clinical diagnosis of diabetes mellitus.

Effect of garlic essential oil in 97 patients hospitalized with covid-19: A multi-center experience.

To observe the synergistic effect of garlic essential oil in patients with novel coronavirus disease (COVID-19), in addition to the routine treatment, we used garlic essential oil in COVID-19 patients with mild to moderate symptoms and compared their results to those of patients who did not receive the essential oil. We conducted a quasi-experimental study with COVID-19 patients from 3 hospitals. In the experimental group, 97 patients received garlic essential oil combined with conventional treatment. In the control group, 100 patients received only the conventional treatment for COVID-19. The effectiveness and safety of the garlic essential oil were assessed. Compared to the control group, the group receiving garlic essential oil showed a shorter duration of symptoms, shorter time to negative nucleic acid testing (NAT) results and shorter time to improvement on the computed tomography (CT). In the same period, the experimental group showed an increase in the rate of the disappearance of symptoms and the improvement rates of NAT and CT. Due to its effectiveness and safety in patients with COVID-19, garlic essential oil is recommended as a preventive measure or a supportive therapy during the COVID-19 pandemic.

Colorimetric detections of iodide and mercuric ions based on a regulation of an Enzyme-Like activity from gold nanoclusters.

A simple colorimetric method was developed for sensitive and selective detections of I- and Hg2+. Histidine stabilized gold nanoclusters (His-AuNCs) were synthesized and catalyzed the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to a blue product. As a strong ligand toward gold, iodide (I-) attached to the surface of the His-AuNCs and significantly enhanced the oxidase-like activity of the His-AuNCs. Based on this enhancement, a sensitive colorimetric response toward I- was obtained. Furthermore, the strong interaction between Hg2+ and I- was adopted for an indirect Hg2+ detection. Under the optimal conditions, the platform presented high selectivity for the determinations of I- and Hg2+ in the ranges 0.02-1 µM and 0.05-0.8 µM, with detection limits as 3.3 nM and 8 nM respectively. This colorimetric assay was successfully applied for analysis of real samples.

Regulatory functions of miR­200b­3p in tumor development (Review).

MicroRNAs (miRNAs/miRs), non­coding single­stranded RNAs of length 18­24 nucleotides, can modulate gene expression through post­transcriptional control. As such, they can influence tumor proliferation, apoptosis, invasion, metastasis as well as chemotherapy resistance by regulating certain downstream genes. In this context, miR­200b­3p, one particular member of the miR­200 family, possesses the ability to suppress tumor progression. However, many studies have suggested that, in certain cases, this miRNA may also promote the development of some tumors due to differences in the microenvironments and molecular backgrounds of different cancers. This review summarizes previous studies on the involvement of miR­200b­3p in tumors, including the underlying mechanism.

Ready-to-Use Colorimetric Platform for Versatile Enzyme Assays through Copper Ion-Mediated Catalysis.

A low cost and versatile colorimetric platform is developed for selective detections of various enzymes. Similar to peroxidases, free copper ion catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 and turns TMB into a blue product. Bindings from ligands toward copper ions inhibit this catalysis. Enzymes catalyze the reactions of related substrates with generation or consumption the ligands for the binding and thus in turn alter the color changes as responses toward the enzymes. With suitable substrates, exemplary enzymes, including trypsin, acid phosphatase, and tyrosinase, can be sensitively measured, with limits of detection of 0.003 µg/mL, 0.004 U/L, and 0.02 U/mL, respectively. This platform is built with directly available reagents, and the signals can be obtained with inexpensive photometers or visual observations. The low cost and convenience make it suitable for cases where complicated instrumentations are not available, such as point-of-care testing.

An ultrasensitive electrochemiluminescent sensing platform for oxygen metabolism based on bioactive magnetic beads.

Reactive oxygen species (ROS), produced during oxygen metabolism, participate in and regulate various life processes. It is of great significance to monitor ROS in biological organs to further study oxygen metabolism. Herein, an ultrasensitive sensing platform is developed with electrochemiluminescent (ECL) signalling by integrating bioactive magnetic beads (BMBs) on indium tin oxide (ITO) coated glass using a magnet. For the first time, AuNPs were successfully deposited on Fe3O4 NPs in situ by reduction of α-ketoglutaric acid (α-KG), therefore the electroactive protein, haemoglobin (Hb) or cytochrome C (Cyt C), was assembled on via covalent bonds. The protein can realize direct electron transfer (DET) and catalyse the redox of ROS, reaching a detection limit of 6.21 µM or 0.6 µM of H2O2. Also Au@Fe3O4 NPs efficiently enhanced the ECL of luminol, promoting the sensing ability for ROS. This simultaneous effect endows the platform with low LOD of ROS for 7.69 nM (Hb), or 1.97 nM (Cyt C). Finally, the feasibility and practicality of the sensing platform were verified by monitoring the ROS released from mouse myocardial tissue.

Sensitive detection of glutathione through inhibiting quenching of copper nanoclusters fluorescence.

A method for a sensitive fluorescence detection of glutathione was established. Glutathione-stabilized copper nanoclusters (CuNCs) were synthesized via a facile process. These CuNCs showed blue fluorescence with a peak around 450 nm. In the presence of p-benzoquinone (PBQ), the electron transfer from the copper nanoclusters to PBQ quenched the fluorescence of the CuNCs. Glutathione (GSH), as a reducing agent, formed a complex with PBQ. This formation inhibited the quenching from PBQ, and a restored fluorescence was obtained. This interaction provided a fluorescence enhancement for the measurement of GSH. Under the optimal condition, linear responses were obtained toward GSH in the ranges of 0.06-6.0 µM, with a limit of detection at 20 nM. This developed assay was easy in operation with high sensitivity and selectivity. The applicability was approved with successful glutathione measurements in real samples.

The TDs/aptamer cTnI biosensors based on HCR and Au/Ti3C2-MXene amplification for screening serious patient in COVID-19 pandemic.

The accurate assay of cardiac troponin I (cTnI) is very important for acute myocardial infarction (AMI), it also can be employed as an effective index for screening serious patients in COVID-19 pandemic before fatal heart injury to reduce the mortality. A ratiometric sensing strategy was proposed based on electrochemiluminescent (ECL) signal of doxorubicin (Dox)-luminol or the electrochemical (EC) signal of methylene blue (MB) vs. referable EC signal of Dox. The bio-recognitive Tro4-aptamer ensures the high specificity of the sensor by affinity binding to catch cTnI, and the tetrahedral DNA (TDs) on Au/Ti3C2-MXene built an excellent sensing matrix. An in situ hybrid chain reaction (HCR) amplification greatly improved the sensitivity. The ratiometric sensing responses ECLDox-luminol/CurrentDox or CurrentMB/CurrentDox linearly regressed to cTnI concentration in the range of 0.1 fM-1 pM or 0.1 fM-500 fM with the limit of detection (LOD) as 0.04 fM or 0.1 fM, respectively. Served as the reference signal, CurrentDox reflected the variation of sensor, it is very effective to ensure the accuracy of detection to obviate the false results. The proposed biosensors show good specificity, sensitivity, reproducibility and stability, have been applied to determine cTnI in real samples with satisfactory results. They are worth looking forward to be used for screening serious patient of COVID-19 to reduce the mortality, especially in mobile cabin hospital.

Effect of the Hypoxia Inducible Factor on Sorafenib Resistance of Hepatocellular Carcinoma.

Sorafenib a multi-target tyrosine kinase inhibitor, is the first-line drug for treating advanced hepatocellular carcinoma (HCC). Mechanistically, it suppresses tumor angiogenesis, cell proliferation and promotes apoptosis. Although sorafenib effectively prolongs median survival rates of patients with advanced HCC, its efficacy is limited by drug resistance in some patients. In HCC, this resistance is attributed to multiple complex mechanisms. Previous clinical data has shown that HIFs expression is a predictor of poor prognosis, with further evidence demonstrating that a combination of sorafenib and HIFs-targeted therapy or HIFs inhibitors can overcome HCC sorafenib resistance. Here, we describe the molecular mechanism underlying sorafenib resistance in HCC patients, and highlight the impact of hypoxia microenvironment on sorafenib resistance.

Detection of silver through amplified quenching of fluorescence from polyvinyl pyrrolidone-stabilized copper nanoclusters.

Silver ion detection with ultra-high sensitivity was established. We synthesized copper nanoclusters (CuNCs) with blue fluorescence through a one-pot process. Instead of a direct quencher toward the CuNCs, silver ions activated the strong oxidation from persulfate and subsequently converted divalent manganese ion into manganese dioxide (MnO2). The surface charges of MnO2 and the CuNCs brought them together and quenched the fluorescence from the latter. Due to silver ions' role as the catalyst in the process, it cycled and even a small amount leads to a significant fluorescence change. This signaling provided the determination of  silver ions in the range 5 pM~1 nM, with a detection limit of  1.2 pM. The method is selective, and its applicability was validated through practical water sample analyses.

Turn-on fluorescence measurement of acid phosphatase activity through an aggregation-induced emission of thiolate-protected gold nanoclusters.

A fluorescence method was developed for a turn-on measurement of acid phosphatase (ACP) activity. It was found that cerous ion (Ce3+) could lead to an enhancement of glutathione protected gold nanocluster fluorescence through an aggregation-induced-emission (AIE) process, while its higher valent counterpart ceric ion (Ce4+) could not. In a weakly acidic environment, ACP catalyzed the dephosphorylation of a phosphate ester of ascorbic acid, with a generation of ascorbic acid (AA). AA reduced Ce4+ into Ce3+, which subsequently enhanced the nanocluster fluorescence. This kind of turn-on fluorescence linearly related to the ACP activity in the range of 0.005-2.4 U/L, with a limit of detection as 0.001 U/L. Human serum samples were measured after a trichloroacetic acid treatment and a simple dilution. The whole analyses were accomplished in 1.5 h with results in good accordance with a reference method.

Th17 Cells in Inflammatory Bowel Disease: Cytokines, Plasticity, and Therapies.

Autoimmune diseases (such as rheumatoid arthritis, asthma, autoimmune bowel disease) are a complex disease. Improper activation of the immune system or imbalance of immune cells can cause the immune system to transform into a proinflammatory state, leading to autoimmune pathological damage. Recent studies have shown that autoimmune diseases are closely related to CD4+ T helper cells (Th). The original CD4 T cells will differentiate into different T helper (Th) subgroups after activation. According to their cytokines, the types of Th cells are different to produce lineage-specific cytokines, which play a role in autoimmune homeostasis. When Th differentiation and its cytokines are not regulated, it will induce autoimmune inflammation. Autoimmune bowel disease (IBD) is an autoimmune disease of unknown cause. Current research shows that its pathogenesis is closely related to Th17 cells. This article reviews the role and plasticity of the upstream and downstream cytokines and signaling pathways of Th17 cells in the occurrence and development of autoimmune bowel disease and summarizes the new progress of IBD immunotherapy.

Determination of dopamine based on its enhancement of gold-silver nanocluster fluorescence.

Dopamine (DA) is one of the most important neurotransmitters in human bodies and its sensitive detection remains a challenge. Herein, protein stabilized gold-silver nanoclusters (Au-AgNCs) were synthesized at first. It was found that the introduction of dopamine lead to a significant enhancement of the fluorescence from the nanoclusters, together with a red-shift of the peak. Through related spectroscopic and electrochemical studies, the fluorescence enhancement was attributed to the reduction of the nanoclusters by dopamine. This enhancement was then adopted for quantitative measurements, and linear responses toward dopamine in the ranges 0.01-1.7 µM and 1.7-10 µM were constructed. A limit of detection was obtained at 6.9 nM. The present study provided a facile and efficient method for the determination of dopamine, and the method was successfully applied for related measurements in serum samples.