Diagnostic accuracy of mac-2-binding protein glycosylation isomer for diagnosing hepatitis B-related fibrosis: A meta-analysis.

OBJECTIVES: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis. The aim of this meta-analysis was to evaluate the accuracy of M2BPGi for predicting hepatitis B virus (HBV)-related liver fibrosis. METHODS: EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure, SinoMED, VIP Database for Chinese Technical Periodicals databases were searched comprehensively for articles published up to March 2022. Quality assessment was carried out in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled diagnostic estimates including sensitivity, specificity, the area under the summary receiver operating characteristic curve (AUROC) were calculated. Before pooling the estimates, the threshold effect was assessed. Subgroup analysis was performed as well. RESULTS: In all, 11 studies including 1836 patients were included. None of the 11 studies met all the criteria of QUADAS-2. The threshold effect was found (r = 0.757, P = 0.011) for predicting HBV-related severe fibrosis. The sensitivity, specificity and AUROC of M2BPGi for the prediction of significant fibrosis were 0.68 (0.65-0.71), 0.67 (0.64-0.70) and 0.741, respectively, while those for predicting cirrhosis were 0.65 (0.57-0.72), 0.79 (0.77-0.81) and 0.792. Additionally, the AUROC of M2BPGi for predicting severe fibrosis reached 0.766. No publication bias was observed. The results of subgroup analyses were similar to the overall results. CONCLUSIONS: M2BPGi has moderate diagnostic accuracy for predicting HBV-related significant fibrosis, severe fibrosis, and cirrhosis. Further studies stratified by etiology, liver inflammation, treatment, etc, are urgently needed.

Antenna effect of pyridoxal phosphate on the fluorescence of mitoxantrone-silicon nanoparticles and its application in alkaline phosphatase assay.

As a kind of sensing and imaging fluorescent probe with the merit of low toxicity, good stability, and environment-friendly, silicon nanoparticles (SiNPs) are currently attracting extensive research. In this work, we obtained mitoxantrone-SiNPs (MXT-SiNPs) with green emission by one-pot synthesis under mild temperature condition. The antenna based on pyridoxal phosphate (PLP) was designed for light-harvesting to enhance the luminescence of MXT-SiNPs and to establish a novel sensing strategy for alkaline phosphatase (ALP). PLP transfers the absorbed photon energy to MXT-SiNPs by forming Schiff base. When PLP is dephosphorized by ALP, the released free hydroxyl group reacts with aldehyde group to form internal hemiacetal, which leads to the failure of Schiff base formation. Based on the relationship between antenna formation ability and PLP hydrolysis degree, the activity of ALP can be measured. A good linear relationship was obtained from 0.2 to 3.0 U/L, with a limit of detection of 0.06 U/L. Furthermore, the sensing platform was successfully used to detect ALP in human serum with recovery of 97.6-106.2%. The rational design of antenna elements for fluorescent nanomaterials can not only provide a new pathway to manipulate the luminescence, but also provide a new direction for fluorescence sensing strategy.

Sodium Alginate Modified Platinum Nanozymes With Highly Efficient and Robust Oxidase-Like Activity for Antioxidant Capacity and Analysis of Proanthocyanidins.

Platinum nanozymes exhibiting highly efficient and robust oxidase-like activity are successfully synthesized and modified using sodium alginate (SA-PtNPs). According to a steady-state dynamic assay, Michaelis-Menton constant (K m ) is calculated as 11.6 µM, indicating that the affinity of SA-PtNPs toward the substrate, 3, 3', 5, 5'-tetramethylbenzidine (TMB), is high. It shows in the paper that SA-PtNPs exhibit a significant oxidant effect on substrate-O2 to produce O 2 • - as an oxidase mimic. Moreover, the oxidase-like activity fluctuated slightly under changes in environmental pH and incubation time, implying that SA can increase the dispersibility and stability of PtNPs. A colorimetric assay for oligomeric proanthocyanidins (OPC) was realized given how few explorations of the former there are. We found that the significant inhibitory effect of OPC on the oxidase-like activity is due to the competitive effect between OPC and TMB for binding to the active site of SA-PtNPs, resulting in a color change. Under optimal conditions, the logarithmic value of the chromogenic difference (ΔA450nm) to OPC concentration was linear (4-32.5 µM, r = 0.999) with a limit of detection (LOD) of 2.0 µM. The antioxidant capacity of OPC obtained by the Soxhlet extraction method from grape seeds was 2.85 U/mg. The recovery from the experiment in which OPC was added to grape seeds ranged from 97.0 to 98.6% (RSDs of 0.5-3.4%), suggesting a high accuracy in OPC detection. These findings are important because OPC is an internationally recognized antioxidant that eliminates free radicals in the human body and, therefore, may prevent a variety of diseases. Thus, we envisage that this Pt nanozyme-based assay may be prevalent for antioxidant capacity evaluation and analytical applications.

Gold nanoclusters/graphene quantum dots complex-based dual-emitting ratiometric fluorescence probe for the determination of glucose.

Herein, we report the design of a single-excitation/double-emission ratiometric fluorescence nanosensor for the determination of glucose. The sensing system combines glucose oxidation catalyzed by glucose oxidase, Fenton chemistry, Fe3+-sensitive fluorescent gold nanoclusters (AuNCs), and Fe3+-inert fluorescent graphene quantum dots (GQDs). We used orange-fluorescent AuNCs co-modified with bovine serum albumin and 3-mercaptopropionic acid as the indicator probe, and GQDs with the same excitation wavelength as the BSA/MPA-AuNCs, but with different emission wavelength, as the reference probe. The fluorescence intensity-ratio between 420 nm and 575 nm (F420/F575) was used to quantitatively determine glucose with a low detection limit of 0.18 µM, and the nanosensor was successfully used to detect glucose in human serum. This ratiometric fluorescence sensing system, based on AuNCs and GQDs, ensures sensitive and convenient determination of glucose, and has broad application prospects for biomedical-analysis applications.

Decisive role of pH in synthesis of high purity fluorescent BSA-Au20 nanoclusters.

Various types of bovine serum albumin (BSA)-protected fluorescent gold nanoclusters (BSA-AuNCs) have been fabricated and applied in various fields. However, the conventional synthesis methods for BSA-AuNCs usually yield a low photoluminescence quantum yield (PLQY) in solution. In this study, we systematically examined the influences of incubation time, temperature, and pH on the formation process of BSA-AuNCs and then developed a novel strategy to synthesize BSA-AuNCs with PLQY (26%), far exceeding that of existing counterparts. Of the three important factors, pH, temperature, and time, pH plays a key role in the formation of BSA-AuNCs with different compositions and fluorescence properties. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) results showed that BSA-Au20NCs with high purity can be produced at a pH value of 10 and the correct combination of incubation temperature and reaction time. The advantages of the obtained BSA-Au20NCs, including small size, high PLQY, long lifetime, high purity, as well as facile modification, make them ideal candidates for luminescent probes in imaging and sensing applications.

Sensitive and selective nitrite assay based on fluorescent gold nanoclusters and Fe2+/Fe3+ redox reaction.

In recent years, gold nanoclusters (AuNCs) have received considerable attention as optical transducers in chemo/biosensors. Herein, a facile and efficient assay for NO2- has been successfully developed based on the fluorescence quenching of AuNCs co-modified by bovine serum albumin and 3-mercaptopropionic acid (BSA/MPA-AuNCs). In the presence of NO2- under acidic conditions, Fe2+ can be readily oxidized and transformed to Fe3+, which can significantly suppress the fluorescence of BSA/MPA-AuNCs via non-radiative electron-transfer mechanism. The linear range and detection limit for this system were found to be 5-30 µM (r = 0.9975) and 0.7 µM, respectively. Other common anions and cations showed only very minor interference with the NO2- detection. Furthermore, the effectiveness of the proposed sensing strategy was validated by the demonstration of good performance in the determination of the amount of NO2- in ham samples, rendering it a powerful tool for the assessment of food security and water quality.

Ascorbate Oxidase Mimetic Activity of Copper(II) Oxide Nanoparticles.

Although oxidase mimetic nanozymes have been widely investigated, specific biological molecules have rarely been explored as substrates, particularly in the case of ascorbate oxidase (AAO) mimetic nanozymes. Herein, we demonstrate for the first time that copper(II) oxide nanoparticles (CuO NPs) catalyze the oxidation of ascorbic acid (AA) by dissolved O2 (as a green oxidant) to form dehydroascorbic acid (DHAA), thus functioning as a new kind of AAO mimic. Under neutral conditions, the Michaelis-Menten constant of CuO NPs (0.1302 mm) is similar to that of AAO (0.0840 mm). Furthermore, the robustness of CuO NPs is greater than that of AAO, thus making them suitable for applications under various conditions. As a demonstration, a fluorescence AA sensor based on the AAO mimetic activity of CuO NPs was developed. To obtain a fluorescent product, o-phenylenediamine (OPDA) was used to react with the DHAA produced by the oxidation of AA catalyzed by CuO NPs. The developed sensor was cost-effective and easy to fabricate and exhibited high selectivity/sensitivity with a wide linear range (1.25×10-6 to 1.125×10-4 m) and a low detection limit (3.2×10-8 m). The results are expected to aid in expanding the applicability of oxidase mimetic nanozymes in a variety of fields such as biology, medicine, and detection science.

Highly sensitive colorimetric sensor for detection of iodine ions using carboxylated chitosan-coated palladium nanozyme.

Although a massive research has been devoted on the exploration of noble metal-based nanozyme, less progress has been made in the investigation of palladium (Pd) nanozyme and the interaction between ions and Pd nanozyme. In this study, a new type of Pd nanozyme was prepared by a facile one-pot approach by using carboxylated chitosan as the stabilizer. Owing to the synergistic effect of carboxylated chitosan stabilized Pd nanoparticles (CC-PdNPs) can effectively catalyze the H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine sulfate (TMB) accompanied by a blue color change (oxidized TMB), indicating the peroxidase-like activity of CC-PdNPs. Furthermore, the Michaelis-Menten constants and catalytic stability of CC-PdNPs render them suitable for environmental analysis and bio-detection. Here, we found that while introducing the iodine ions (I-) into the reaction medium, the peroxidase-like activity of CC-PdNPs has been rapidly and effectively inhibited through the formation of Pd-I bond; thus, the active sites of PdNPs can be blocked by I-. Based on this specific inhibition by I-, a facile colorimetric assay has been performed for the detection of I- with an extremely low limit of detection (0.19 nM). Furthermore, the practicality of the proposed sensor also has been demonstrated in tap water, and the satisfactory recoveries were obtained. Our study not only demonstrated a novel Pd-based nanozyme but also provided guidance for I- sensing for environmental analysis, food inspection, and bio-detection. Graphical abstract.

[Diagnostic Value of MPV, PDW, PAIg and Their Combination for Megakaryocyte Dysmaturity in Children with Acute Immune Thrombocytopenic Purpura].

OBJECTIVE: To investigate the changes of mean platelet volume (MPV), platelet distribution width (PDW) and platelet associated antibodies (PAIg) in children with acute immune thrombocytopenic purpura (aITP), and to explore the diagnostic value of MPV, PDW, PAIg and their combination for megakaryocyte dysmaturity in aITP children. METHODS: Plt count, MPV and PDW of 36 aITP children were measured by using Sysmex XN automatic blood cell analyzer, and 33 children with acquired thrombocytopenic purpura (ATP) without megakaryocyte dysmaturity. The expression of PAIg was detected by flow cytometry, and the number and classification of megakaryocytes in the bone marrow were performed by marrow cytology. The diagnostic significances of MPV, PDW, PAIg and their combination as well as the sensitivity and specificity for megakaryocytes dysmaturity in aITP were assessed through calculating the area under ROC curve (AUC), after determining the influence of each parameters on the megakaryocyte dysmaturity by Logistic regression. RESULTS: MPV, PDW and PAIg of aITP children were significantly higher than those of the ATP children (P＜0.05), while the Plt count and number of thromocytogenic megakaryocytes per area (1.5 cm×3 cm) were less than those of the controls (P＜0.05). Count of RBC and WBC, percentages of neutrophil granulocytes and lymphocydes in aITP were similar to those in the controls（P＞0.05）. The results of Logistic regression showed that Plt count, MPV, PDW and PAIg were the factors influencing megakaryocyte dysmaturity in aITP children, and the regression model has a high statistical significance (χ2=65.491，P=0.001) and r square (R2=0.713). The AUC of the combined detection of Plt count, MPV, PDW and PAIg was 0.863, which was much higher than that of Plt count, MPV, PDW, PAIg individually or in pairs. The sensitivity and specificity of the combined detection were 79.167% and 89.697%, which were higher than those of Plt count, MPV, PDW, PAIg individually or in pairs. CONCLUSION: The diagnostic significance of MPV and PDW for megakaryocyte dysmaturity in aITP are insufficient, but the diagnostic efficacy can be improved by combined examination with PAIg.

Diagnostic accuracy of γ-glutamyl transpeptidase-to-platelet ratio for predicting hepatitis B-related fibrosis: a meta-analysis.

BACKGROUND AND AIM: Emerging published data on the accuracy of γ-glutamyl transpeptidase-to-platelet ratio (GPR) for diagnosing hepatitis B virus (HBV)-related fibrosis are inconsistent. The aim of this study was to systematically review the performance of GPR for diagnosing HBV-related significant fibrosis, severe fibrosis, and cirrhosis. PATIENTS AND METHODS: A comprehensive literature search of PubMed, Web of Science, and EMBASE was conducted before July 2018. Study selection was performed according to inclusion and exclusion criteria. The relevant parameters of eligible studies were abstracted. The methodological quality was assessed according to the Quality Assessment of Diagnostic Accuracy Studies. Areas under summary receiver operating characteristic curves, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratios were used to examine the GPR accuracy for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis. RESULTS: A total of 10 studies including 5882 patients with HBV infection underwent liver biopsy were incorporated. The prevalence of significant fibrosis, severe fibrosis, and cirrhosis were 58% (range: 22-72%), 36% (range: 10-55%), and 19% (range: 2-33%), respectively. Areas under summary receiver operating characteristic curves of GPR for predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.733, 0.777, and 0.796, respectively. Subgroup analysis was performed according to geographical region and histological scoring system with similar results. CONCLUSION: GPR has moderate diagnostic accuracy for predicting HBV-related significant fibrosis, severe fibrosis, and cirrhosis, and further studies with large sample size, rigorous design, multicenter study population are urgently needed.

Fabrication of ultra-small monolayer graphene quantum dots by pyrolysis of trisodium citrate for fluorescent cell imaging.

BACKGROUND: The preparation and biological applications of ultra-small graphene quantum dots (GQDs) with accurate-controlled size are of great significance. METHODS: Here in, we report a novel procedure involving pyrolysis of trisodium citrate and subsequent ultrafiltration for fabricating monolayer GQDs with ultra-small lateral size (1.3±0.5 nm). RESULTS: The GQDs exhibit blue photoluminescence with peak position independent of excitation wavelength. The quantum yield of GQDs is measured to be 3.6%, and the average fluorescence lifetime is 2.78 ns. CONCLUSION: Because of high stability and low toxicity, GQDs are demonstrated to be excellent bioimaging agents. The ultra-small GQDs can not only distribute in the cytoplasm but also penetrate into the nuclei. We ensure that this work will add a new dimension to the application of graphene materials for nanomedicine.

Discussion on Treatment of Post-thyroidectomy Cough Based on Wind, Phlegm, Congestion, and Innutrition / 中国中医药信息杂志

The incidence of thyroid nodule is increasing day by day, and surgery is the main remedy at present. However, patients have a very high incidence of cough. Western medicine has no effective measures, while TCM has good efficacy. Combined with constitutions of thyroid patients and its unique postoperative changes, this article discussed the etiology and treatment of post-thyroidectomy cough from the aspects of "wind", "phlegm","congestion", and "innutrition".

Alkaline peroxidase activity of cupric oxide nanoparticles and its modulation by ammonia.

We herein report the intrinsic alkaline peroxidase-like activity exhibited by CuO nanoparticles when 3-(4-hydroxyphenyl)propionic acid was employed as a substrate. Based on this observation, a fluorometric assay method with a low detection limit of 0.81 µM was established for H2O2 determination under alkaline conditions. Notably, ammonia was found to inhibit the alkaline peroxidase-like activity of the CuO nanoparticles. Thus, a sensing platform for the determination of urea and urease was successfully constructed, with the limits of detection for urea and urease being 27 µM and 2.6 U L-1, respectively. This platform was then applied for the detection of urea in human urine and urease in soil, which yielded satisfactory results. These results suggest that it is possible to extend the catalytic potential of peroxidase and its mimetics from acidic and neutral conditions to include activity in alkaline media as well. Furthermore, this strategy is a novel method for the analysis of urea and urease. The assay developed in this work is facile, inexpensive, convenient, and highly selective and sensitive. Therefore, it is expected that this system can serve as a template for the development of similar enzyme nano-mimics.

Self-cascade reaction catalyzed by CuO nanoparticle-based dual-functional enzyme mimics.

It is desirable but challenging to assemble various biomimetic properties into a functional catalytic cascade system. In this work, cupric oxide nanoparticles were investigated as oxidase mimics for the aerobic oxidation of cysteine to cystine with the generation of hydrogen peroxide. Coupling this property with the peroxidase-like activity of CuO nanoparticles, we constructed a self-organized cascade reaction system based on a single-component nanozyme, which includes the oxidation of cysteine to yield cystine and hydrogen peroxide and the hydrogen peroxide-mediated oxidation of terephthalic acid to produce a fluorescence change. Based on this artificial enzymatic cascade reaction system, a fluorometric assay method with a low detection limit of 6.6nM was established for cysteine determination. This platform was then applied for the detection of cysteine in pharmaceutical products and human plasma, which yielded satisfactory results. Our investigations open up a new route and holds promise for the development and applications of multifunctional nanomaterials as enzyme mimics.

Colorimetric detection of urea, urease, and urease inhibitor based on the peroxidase-like activity of gold nanoparticles.

Herein, we reported for the first time that gold nanoparticles-catalyzed 3,3',5,5'-tetramethylbenzidine-H2O2 system can serve as an ultrasensitive colorimetric pH indicator. Gold nanoparticles acted as a catalyst and imitated the function of horseradish peroxidase. The absorbance at 450 nm of the yellow-color product in the catalytic reaction exhibited a linear fashion over the pH range of 6.40-6.60. On the basis of this property, we constructed a novel sensing platform for the determination of urea, urease, and urease inhibitor. The limit of detection for urea and urease was 5 µM and 1.8 U/L, respectively. The half-maximal inhibition value IC50 of acetohydroxamic acid was found to be 0.05 mM. Urea in human urine and urease in soil were detected with satisfied results.

Partially reduced graphene oxide as highly efficient DNA nanoprobe.

This work investigates the effect of reduction degree on graphene oxide (GO)-DNA interaction and the fluorescence quenching mechanism. Partial reduced graphene oxide (pRGO), which maintains well water-dispersibility, is synthesized using a mild reduction method by incubating GO suspension under alkaline condition at room temperature. The fluorescence quenching enhances with the restoration degree of sp(2) carbon bonds and follows the static quenching mechanism. The binding constant values imply that pRGO has much stronger affinity with ssDNA than GO. Utilizing this highly efficient nanoprobe, a universal sensing strategy is proposed for homogeneous detection of DNA. Compared with the reported GO-based DNA, this present strategy has obvious advantages such as requirement of low nanoprobe dosage, significantly reduced background, fast fluorescence quenching, and improved sensitivity. Even without any amplification process, the limit of detection can reach as low as 50 pM.

Fluorescent hydrogen peroxide sensor based on cupric oxide nanoparticles and its application for glucose and L-lactate detection.

A novel fluorescent hydrogen peroxide sensor was developed based on the peroxidase-like activity of cupric oxide nanoparticles. Cupric oxide nanoparticles effectively catalyzed the decomposition of hydrogen peroxide into hydroxyl radicals. Then terephthalic acid was oxidized by hydroxyl radical to form a highly fluorescent product. The linear range of hydrogen peroxide estimated to be 5.0 × 10(-6)-2.0 × 10(-4)M with a detection limit of 3.4 × 10(-7)M. Moreover, this detection system enabled the sensing of analytes which can enzymatically generate hydrogen peroxide. By coupling the oxidation of glucose or L-lactate catalyzed by their corresponding oxidase enzymes with terephthalic acid oxidation catalyzed by cupric oxide nanoparticles, sensitive assays of glucose and l-lactate with detection limits of 1.0 × 10(-6) and 4.5 × 10(-8)M were realized. The successful applications of this approach in human serum samples have also been demonstrated.

PRSS1_p.Leu81Met mutation results in autoimmune pancreatitis.

AIM: To describe protease serine 1 (PRSS1) gene mutations in patients with autoimmune pancreatitis (AIP) and the clinical features of AIP. METHODS: Fourteen patients with AIP, 56 with other chronic pancreatitis, 254 with pancreatic cancer and 120 normal controls were studied. The mutations and polymorphisms of four genes involved with pancreatitis or pancreatic cancer, PRSS1, SPINK1, CFTR and MEN1, were sequenced. The pathogenic mechanism of AIP was investigated by comparing the wild-type expression system with the p.81Leu→Met mutant expression system. RESULTS: Two novel mutations (p.81Leu→Met and p.91Ala→Ala) were found in PRSS1 gene from four patients with AIP. PRSS1_p.81Leu→Met mutation led to a trypsin display reduction (76.2%) combined with phenyl agarose (Ca(2+) induced failure). Moreover, the ratio of trypsin/amylase in patients with AIP was higher than in the patients with pancreatic cancer and other pancreatitis. A large number of lymphocytes and plasma cells were found in the bile ducts accompanied by hyperplasia of myofibroblasts. CONCLUSION: Autoimmune pancreatitis may be related to PRSS1 gene mutations.