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Quan-Quan Zhuang,1 Zhi-Hang Lin,1 Yan-Cheng Jiang,1 Hao-Hua Deng,2 Shao-Bin He,1,3 Li-Ting Su,4 Xiao-Qiong Shi,2 Wei Chen2 1Department of Pharmacy, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, 2Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 3Department of Pharmacy, Quanzhou Infectious Disease Hospital, 4Department of Pharmaceutical Analysis, Quanzhou Medical College, Quanzhou, People’s Republic of China Abstract: Dendrite-like cobalt selenide nanostructures were synthesized from cobalt and selenium powder precursors by a solvothermal method in anhydrous ethylenediamine. The as-prepared nanocrystalline cobalt selenide was found to possess peroxidase-like activity that could catalyze the reaction of peroxidase substrates in the presence of H2O2. A spectrophotometric method for uric acid (UA) determination was developed based on the nanocrystalline cobalt selenide-catalyzed coupling reaction between N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt and 4-aminoantipyrine (4-AAP) in the presence of H2O2. Under optimum conditions, the absorbance was proportional to the concentration of UA over the range of 2.0–40 µM with a detection limit of 0.5 µM. The applicability of the proposed method has been validated by determination of UA in human serum samples with satisfactory results. Keywords: enzyme mimics, cobalt selenide, peroxidase-like activity, uric acid, human serum

α-Glucosidase (α-Glu) is implicated in the progression and pathogenesis of type II diabetes (T2D). In this study, we developed a rapid colorimetric technique using platinum nanoparticles stabilized by chitosan (Ch-PtNPs) to detect α-Glu activity and its inhibitor. The Ch-PtNPs facilitate the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB (oxTMB) in the presence of dissolved O 2 . The catalytic hydrolysis of 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) by α-Glu produces ascorbic acid (AA), which reduces oxTMB to TMB, leading to the fading of the blue color. However, the presence of α-Glu inhibitors (AGIs) hinders the generation of AA, allowing Ch-PtNPs to re-oxidize colorless TMB back to blue oxTMB. This unique phenomenon enables the colorimetric detection of α-Glu activity and AGIs. The linear range for α-Glu was found to be 0.1-1.0 U mL -1 and the detection limit was 0.026 U mL -1 . Additionally, the half-maximal inhibition value (IC 50 ) for acarbose, an α-Glu inhibitor, was calculated to be 0.4769 mM. Excitingly, this sensing platform successfully detected α-Glu activity in human serum samples and effectively screened AGIs. These promising findings highlight the potential application of the proposed strategy in clinical diabetes diagnosis and drug discovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Developing sensor arrays capturing comprehensive fluorescence (FL) spectra from a single probe is crucial for understanding sugar structures with very high similarity in biofluids. Therefore, the analysis of highly similar sugar' structures in biofluids based on the entire FL of a single nanozyme probe needs more concern, which makes the development of novel alternative approaches highly wanted for biomedical and other applications. Herein, a well-designed deep learning model with intrinsic information of 3D FL of CuO nanoparticles (NPs)' oxidase-like activity was developed to classify and predict the concentration of a group of sugars with very similar chemical structures in different media. The findings presented that the overall accuracy of the developed model in classifying the nine selected sugars was (99-100 %), which prompted us to transfer the developed model to predict the concentration of the selected sugars at a concentration range of (1-100 μM). The transferred model also gave excellent results (R 2  = 97-100 %). Therefore, the model was extended to other more complex applications, namely the identification of mixtures of sugars in serum and the detection of polysaccharides in different media such as serum and lake water. Notably, LOD for fructose was determined at 4.23 nM, marking a 120-fold decrease compared to previous studies. Our developed model was also compared with other deep learning-based models, and the results have demonstrated remarkable progress. Moreover, the identification of other possible coexisting interference substances in lake water samples was considered. This work marks a significant advancement, opening avenues for the widespread application of sensor arrays integrating nanozymes and deep learning techniques in biomedical and other diverse fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydroxyl radical (·OH) scavenging capacity (HOSC) estimation is essential for evaluating antioxidants, natural extracts, or drugs against clinical diseases. While nanozymes offer advantages in related applications, they still face limitations in activity and selectivity. In response, this work showcases the fabrication of laminarin-modulated osmium (laminarin-Os) nanoclusters (1.45 ± 0.05 nm), functioning as peroxidase-like nanozymes within a colorimetric assay tailored for rational HOSC estimation. This study validates both the characterization and remarkable stability of laminarin-Os. By leveraging the abundant surface negative charges of laminarin-Os and the surface hydroxyls of laminarin, oxidation reactions are facilitated, augmenting laminarin-Os's affinity for 3,3',5,5'-tetramethylbenzidine (TMB) (K M  = 0.04 mM). This enables the laminarin-Os-based colorimetric assay to respond to ·OH more effectively than citrate-, albumin-, or other polysaccharides-based Os. In addition, experimental results also validate the selective peroxidase-like behavior of laminarin-Os under acidic conditions. Antioxidants like ascorbic acid, glutathione, tannic acid, and cysteine inhibit absorbance at 652 nm in the colorimetric platform using laminarin-Os's peroxidase-like activity. Compared with commercial kits, this assay demonstrates superior sensitivity (e.g., responds to ascorbic acid 0.01-0.075 mM, glutathione 1-15 µg/mL, tannic acid 0.5-5 µM, and monoammonium glycyrrhizinate cysteine 1.06-10.63 µM) and HOSC testing for glutathione, tannic acid, and monoammonium glycyrrhizinate cysteine. Overall, this study introduces a novel Os nanozyme with exceptional TMB affinity and ·OH selectivity, paving the way for HOSC estimation in biomedical research, pharmaceutical analysis, drug quality control, and beyond., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Osteoporotic vertebral compression fractures (OVCFs) contribute to back pain and functional limitations in older individuals, with percutaneous vertebroplasty (PVP) emerging as a minimally invasive treatment. However, further height loss post-PVP prompts investigation into contributing factors., Aim: To investigate the factors associated with further height loss following PVP with cement augmentation in OVCF patients., Methods: A total of 200 OVCF patients who underwent successful PVP between January 2021 and December 2022 were included in this study. "Further height loss" during 1 year of follow-up in OVCF patients with bone edema was defined as a vertical height loss of ≥ 4 mm. The study population was divided into two groups for analysis: The "No Further Height Loss group ( n = 179)" and the "Further Height Loss group ( n = 21).", Results: In comparing two distinct groups of patients, significant differences existed in bone mineral density (BMD), vertebral compression degree, prevalence of intravertebral cleft (IVF), type of bone cement used, and cement distribution patterns. Results from binary univariate regression analysis revealed that lower BMD, the presence of IVF, cleft distribution of bone cement, and higher vertebral compression degree were all significantly associated with further height loss. Notably, the use of mineralized collagen modified-poly(methyl methacrylate) bone cement was associated with a significant reduction in the risk of further height loss. In multivariate regression analysis, lower BMD and the presence of IVF remained significantly associated with further height loss., Conclusion: Further height loss following PVP in OVCF patients is influenced by a complex interplay of factors, especially lower BMD and the presence of IVF. These findings underscore the importance of assessing and managing these factors when addressing height loss following PVP in OVCF patients., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the optimization of surgical procedures for laryngotracheal stenosis and its effect analysis. Methods: The data of 32 patients with acquired laryngotracheal stenosis who received surgical treatment from October 2015 to December 2021 were analyzed retrospectively. The age ranged from 19 to 72 years, with an average of (34.0±9.0) years. The medical history ranged from 1 to 32 months (median 3 months). As for etiology, there were 30 cases of iatrogenic laryngotracheal stenosis, including 20 cases of tracheal intubation and 10 cases of tracheotomy (7 cases of percutaneous tracheotomy and 3 cases of traditional tracheotomy). There were 1 case of laryngotracheal trauma and 1 case of airway Penicillium marneffei infection. According to Myer-Cotton grading system, grade Ⅳ stenosis was found in 14 cases, including 12 cases involving trachea and 2 cases involving trachea and subglottic area.There were 18 cases of grade Ⅲ, all of which involved the cervical trachea 5 cases failed in operation in other hospitals. According to stenosis grading, course of disease, primary disease control and the patient's general condition, the surgical plan was determined individually. The operations of end-to-end anastomosis, circumferential tracheal partial resection, T-tube placement and CO 2 laser tracheal scar resection were performed respectively. The recovery of airway function and perioperative complications were observed one year after operation. Results: End-to-end anastomosis was performed in 16 cases, and partial circumferential tracheal resection in 2 cases, and tracheal granulation (scar) resection by CO 2 laser in 2 cases and T-tube insertion in 12 cases. Eighteen cases which performed end-to-end anastomosis, partial resection of circumferential trachea in and 2 cases which performed laser tracheal scar resection were all recovered airway function at one stage. After 1 year, 19 cases were cured and 1 case was effective. Of 12 patients with T tube implantation, 11 cases were successfully extubated after 6-12 months, 7 cases were cured after 1 year, 2 cases were effective and 3 cases were ineffective. Among the 3 cases of failure, 2 cases were successfully extubated by sleeve resection and end-to-end anastomosis in the second stage, and the other case refused to accept other treatment methods and the T-tube was placed again, and the tube was blocked and the patient survived. During the follow-up period, the total cure rate was 87.5%, the effective rate was 9.4%, and the total extubation rate was 96.9%.The most common complication was subcutaneous emphysema, accounting for 78% (25/32), but no serious mediastinal emphysema or pneumothorax occurred. In the T-tube implantation group, granulation tissue grew in different degrees around the neck wound after operation, and improved or disappeared after 6-9 months. Anterior cervical tracheal fistula occurred in 4 cases of T-tube implantation group after extubation, which were cured by sealing the stoma. There were no complications such as severe bleeding or perioperative death. Conclusion: When there were various factors, the optimization of the surgical plan according to the degree of stenosis, the course of disease, the control of primary disease and the general condition was an important guarantee to improve the curative effect of laryngotracheal stenosis.

Respiratory diseases, some of the most common human diseases, have become a prominent public health and medical problem. Feasible treatment and prevention strategies are still required to prepare for respiratory emergencies. Nanotechnology has provided new technological conceptions in respiratory disease-related applications and inspired the exploration of various multifunctional nanomaterials. Among them, "nanozymes" with enzyme-like activities and nanomaterials' physicochemical properties may propel the development in this field. Over the past few decades, nanozymes have distinguished themselves in the fields of biosensing, biomedicine, imaging, and environmental protection due to their outstanding enzymatic properties, reactive oxygen species-regulating mechanism, high stability, modifiability, mass production, and others. Herein, this article reviews the research progress of nanozymes in diagnosing, treating, and preventing respiratory diseases, hoping to bring new ideas for promoting nanozymes and their beneficial applications in respiratory diseases.

Selenium is an essential micronutrient element. For the extremely biotoxic of selenite, Selenium nanoparticles (SeNPs) is gaining increasing interest. In this work, a selenium-enriched strain with highly selenite-resistant (up to 173 mmol/L) was isolated from the local specialty food of longevity area and identified as Paenibacillus motobuensis (P. motobuensis) LY5201. Most of the SeNPs were accumulated extracellular. SeNPs were around spherical with a diameter of approximately 100 nm. The X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy showed that the purified SeNPs consisted of selenium and proteins. Our results suggested that P. motobuensis LY5201could be a suitable and robust biocatalyst for SeNPs synthesis. In addition, the cytotoxicity effect and the anti-invasive activity of SeNPs on the HepG2 showed an inhibitory effect on HepG2, indicating that SeNPs could be used as a potential anticancer drug., (© 2022. The Author(s).)

Chitosan modification has attracted considerable interest in the nanozyme field last decade. As a chitosan derivative, carboxylated chitosan (CC) has been less explored. Herein, PtNPs with an average size of approximately 3.3 nm and zeta potential of -44.8 ± 0.3 mV (n = 3) have been prepared by using CC as the surface modification (CC-PtNPs). We have carried out an in-depth investigation of CC-PtNPs, including the characterization, colloidal stability, and ascorbate oxidase-like activity. Due to the contribution of carboxylated chitosan, CC-PtNPs present improved colloidal stability and ascorbate oxidase-like activity compared to chitosan-modified Pt nanozyme. Inspired by these results, a fluorometric acid phosphatase sensor was proposed based on the improved performance of CC-PtNPs. This sensor exhibits excellent sensitivity and selectivity towards acid phosphatase in the linear range of 0.25-18 U/L with a low limit of detection (1.31 × 10 -3  U/L). The concentration of acid phosphatase in human semen samples has been successfully measured., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2022. Published by Elsevier Ltd.)

Different acquisition data approaches have been used to fetch the fluorescence spectra. However, the comparison between them is rare. Also, the extendability of a sensor array, which can work with heavy metal ions and other types of analytes, is scarce. In this study, we used first- and second-order fluorescent data generated by 6-Aza-2-thiothymine-gold nanocluster (ATT-AuNCs) as a single probe along with machine learning to distinguish between a group of heavy metal ions. Moreover, the dimensionality reduction was carried out for the different acquisition data approaches. In our case, the accuracy of different machine learning algorithms using first-order data outperforms the second-order data before and after the dimensionality reduction. For proving the extendibility of this approach, four anions were used as an example. As expected, the same finding has been found. Furthermore, random forest (RF) showed more stable and accurate results than other models. Also, linear discriminant analysis (LDA) gave acceptable accuracy in the analysis of the high-dimensionality data. Accordingly, using LDA in high-dimensionality data (the first- and second-order data) analysis was highlighted for discrimination between the selected heavy metal ions in different concentrations and in different molar ratios, as well as in real samples. Also, the same method was applied for the anion's discrimination, and LDA gave an excellent separation ability. Moreover, LDA was able to differentiate between all the selected analytes with excellent separation ability. Additionally, the quantitative detection was considered using a wide concentration range of Cd 2+ , and the LOD was 60.40 nM. Therefore, we believe that our approach opens new avenues for linking analytical chemistry, especially sensor array chemistry, with machine learning., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Clear cell renal cell carcinoma (ccRCC) is a worldwide malignancy with high morbidity and mortality. Translation initiation factor 4A1 (eIF4A1), which is an ATP-dependent RNA helicase as a part of eIF4F complex, has been linked to malignant transformation and progression, and a variety of cancers display dysregulation of this enzyme. However, its role in ccRCC remains unclear. In our study, we examined its potential effects in ccRCC., Methods: Based on Proteomic data, TCGA and ONCOMINE database, RCC cell lines and tissues, the expression of eIF4A1 between ccRCC and normal tissues were investigated. A correlation was evaluated between the prognostic model for OS and ccRCC progression. Analysis of functional enrichment and PPI network were performed. After examining differentially expressed genes between the eIF4A1 high and low-expression groups, we performed GSEA analysis. Furthermore, we investigated immune cell infiltration of eIF4A1. Then we determined eIF4A1 functions in the establishment and maintenance of cell viability, migration and invasion of cell lines. Flow cytometry was utilized to detect cell cycle., Results: The eIF4A1 was up-regulated in ccRCC tissues and cell lines. An increased level of eIF4A1 was linked to lower survival rates and impaired immunity. Depletion of eIF4A1 could arrest tumor cells in G1 phase, so as to seriously limit cell proliferation and weaken the capacity of cell migration., Conclusion: ccRCC patients with high eIF4A1 expression are at increased risk of poor prognosis, furthermore eIF4A1 plays a prominent role in facilitating tumor cell proliferation and migration which may further be a potential prognostic biomarker and therapeutic target., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

A surge of nanozymes with oxidase-like activities is emerging in various fields, whereas nanozymes with the ability to catalyze the oxidation of saccharides have less been explored. Herein, CuO nanoparticles (NPs) with phosphate-supported fructose oxidase-like activity have been reported. Notably, reactive oxygen species (ROS) have been confirmed as the products during the process. By coupling the fructose oxidase-like activity with the peroxidase-like activity of CuO NPs, a tandem catalysis-based fructose sensor can be fabricated. In detail, CuO NPs can catalyze the fructose oxidation under O 2 to yield ROS (e.g., H 2 O 2 , •OH, and O 2 ·- ) and effectively decompose H 2 O 2 into ·OH. After that, terephthalic acid can be oxidized by •OH produced from the tandem catalysis to generate a fluorescent product. This sensor shows a linear range toward fructose (0.625-275 μМ) with a low limit of detection (0.5 μМ), which can be successfully conducted to detect fructose from real samples. Overall, this work aims to expand the catalytic types of nanozymes and provide a desirable fructose sensor., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sensitive and rapid detection of pathogenic bacteria plays an important role in avoiding food poisoning. However, the practical application value of conventional assays for detection of foodborne bacteria, are limited by major drawbacks; these include the laboriousness of pure culture preparation, complexity of DNA extraction for polymerase chain reaction, and low sensitivity of enzyme-linked immunosorbent assay. Herein, we designed a non-complex strategy for the sensitive, quantitative, and rapid detection of Salmonella typhimurium with high specificity, using an anti-Salmonella typhimurium IgG-AuNC-based immunofluorescent-aggregation assay. Salmonella typhimurium was agglutinated with fluorescent anti-Salmonella typhimurium IgG-AuNC on a glass slide, and observed using a fluorescence microscope with photoexcitation and photoemission at 560 nm and 620 nm, respectively. Under optimized reaction conditions, the AuNC-based immunofluorescent-aggregation assay had a determination range between 7.0 × 10 3 and 3.0 × 10 8  CFU/mL, a limit of detection of 1.0 × 10 3  CFU/mL and an assay response time of 3 min. The technique delivered good results in assessing real samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Rhizosphere and endophytic microbiota significantly affect plant growth and development by influencing nutrient uptake and stress tolerance. Herein, root and rhizosphere soil of Acacia species were collected and analyzed to compare the structural differences of the rhizosphere and root endophytic bacterial communities. High-throughput 16S rRNA gene sequencing technology was employed to analyze the rhizosphere and root endophytic bacterial communities. A total of 4249 OTUs were identified following sequence analysis. The rhizosphere soil contained significantly more OTUs than the root soil. Principal component analysis (PCA) and hierarchical cluster analysis indicated that bacterial communities exhibited significant specificity in the rhizosphere and root soil of different Acacia species. The most dominant phylum in the rhizosphere soil was Acidobacteria, followed by Proteobacteria and Actinobacteria, whereas the dominant phylum in the root soil was Proteobacteria, followed by Actinobacteria and Acidobacteria. Among the various Acacia species, specific bacterial communities displayed different abundance. We systematically described the core bacteria in the rhizosphere and root endophytic bacterial communities and predicted their relevant functions. The type and abundance of specific bacteria were correlated with the nutrient absorption and metabolism of the Acacia species. This study addresses the complex host-microbe interactions and explores the rhizosphere and root bacterial community structure of different Acacia species. These results provide new insights into the role of rhizosphere and root endophytic bacterial communities on the growth and reproduction of Acacia, thus informing future efforts towards sustainable development and utilization of Acacia., Competing Interests: The authors have declared that no competing interests exist.

Heavy metal ions (HMIs), including Cu 2+ , Ag + , Cd 2+ , Hg 2+ , and Pb 2+ from the environment pose a threat to human beings and can cause a series of life-threatening diseases. Therefore, colorimetric sensors with convenience and flexibility for HMI discrimination are still required. To provide a solution, a peroxidase-like activity-based colorimetric sensor array of citrate-capped noble metal nanozymes (osmium, platinum, and gold) has been fabricated. Some studies reported that some HMIs could interact with the noble metal nanozymes leading to a change in their peroxidase-like activity. This phenomenon was confirmed in our work. Based on this principle, different concentrations of HMIs (Cu 2+ , Ag + , Cd 2+ , Hg 2+ , and Pb 2+ ) were discriminated. Moreover, their practical application has been tested by discriminating HMIs in tap water and SiYu lake water. What is more, as an example of the validity of our method to quantify HMIs at nanomolar concentrations, the LOD of Hg 2+ was presented. To sum up, our study not only demonstrates the differentiation ability of this nanozyme sensor array but also gives hints for using nanozyme sensor arrays for further applications.

Extensive studies have laid the groundwork for understanding peroxidase-like nanozymes. However, improvements are still required before their practical applications. On one hand, it is significant to explore highly reactive nanozymes. On the other hand, it is necessary to avoid fouling formed on the surface of nanozymes, which will affect their activity and the results of H 2 O 2 sensors or H 2 O 2 -related applications. Herein, a strategy is reported to design osmium nanoclusters (Os NCs) with the existence of bovine serum albumin (BSA) through biomineralization. BSA-Os NCs were found to possess intrinsic peroxidase-like activity with a high specific activity (6120 U/g). Studies also found that the catalytic activity of BSA-Os NCs was better than those of reported protein-assisted metal nanozymes (e.g., BSA-Pt NPs and BSA-Au NCs). More significantly, BSA has been confirmed as a protective shell to give Os NCs extrinsic antifouling property in some typical ions (e.g., Hg 2+ , Ag + , Pb 2+ , I - , Cr 6+ , Cu 2+ , Ce 3+ , S 2- , etc.), saline (0-2 M), or protein (0-100 mg/mL) conditions. Under optimal conditions, a colorimetric sensor was established to realize a linear range of H 2 O 2 from 1.25 to 200 μM with a low detection limit of 300 nM. On this basis, remarkable features enable a BSA-Os NCs-based colorimetric sensor to detect H 2 O 2 from complex systems with clear color gradients. Together, this work highlights the advantages of protein-assisted Os nanozymes and provides a paragon for peroxidase-like nanozymes in H 2 O 2 -related applications.

In this study, the immunomodulatory effect of sea buckthorn (SBT) pulp oil was elucidated in immunosuppressed Balb/c mice induced by cyclophosphamide (CTX). The results showed that SBT pulp oil could reverse the decreasing trend of body weight, thymus/spleen index and hematological parameters induced by CTX. Compared with immunosuppressive mice induced by CTX, SBT pulp oil could enhance NK cytotoxicity, macrophage phagocytosis, and T lymphocyte proliferation, and regulate the proportion of T cell subsets in mesenteric lymph nodes (MLN), and promote the production of secretory immunoglobulin A (sIgA), IFN-γ, IL-2, IL-4, IL-12 and TNF-α in the intestines. In addition, SBT pulp oil can promote the production of short fatty acids (SCFAs), increase the diversity of gut microbiota, improve the composition of intestinal flora, increase the abundance of Alistipes, Bacteroides, Anaerotruncus, Lactobacillus, ASF356, and Roseburia, while decreasing the abundance of Mucispirillum, Anaeroplasma, Pelagibacterium, Brevundimonas, Ochrobactrum, Acinetobacter, Ruminiclostridium, Blautia, Ruminiclostridium, Oscillibacter, and Faecalibaculum. This study shows that SBT pulp oil can regulate the diversity and composition of intestinal microflora in CTX-induced immunosuppressive Balb/c mice, thus enhancing the intestinal mucosa and systemic immune response. The results can provide a basis for understanding the function of SBT pulp oil and its application as a new probiotic and immunomodulator.

Objective: To treat children with acute nonsuppurative otitis media induced by acute upper respiratory tract infection of varying severity and evaluate its therapeutic effects., Materials and Methods: Patients from the emergency department with acute nonsuppurative otitis media were followed up between September 2015 and December 2018. A total of 420 patients were classified into grades I to III according to tympanic membrane intactness and systemic reactions and treated according to grading., Results: Grade I patients showed no significant difference in the recovery of acute symptoms whether antibiotics are used or not. Grade II patients, after 3 months of follow-up, showed no tympanic membrane perforation, and 9 cases of binaural B-type children did not improve but were cured by operation. In grade III patients, after treatment for 4 hours in the experimental group 3, the earache subsided, 1 case had tympanic membrane perforation, and the patients recovered after 2 weeks (64/92) and after 3 months (28/92) of drug treatment. After treatment for 4 h in the control group 3, the earache eased, and 3 patients developed tympanic membrane perforation and were treated for 3 months. 4 binaural B-type children did not improve but recovered after surgical treatment., Conclusion: Grade I patients could be closely followed up by clinical observation. For anti-inflammatory patients with grade II disease, treatment has therapeutic significance. For patients with grade III, some patients still have TMP, but the use of cephalosporin third-generation drugs plus an appropriate amount of hormone therapy is effective in reducing symptoms and tympanic local reactions., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Wei Meng et al.)

Background: Liver metastasis of colorectal cancer (CRC) is an important cause of death from CRC, but its molecular mechanism is still unclear. In recent years, whole-exome sequencing has played an increasingly important role in the study of the occurrence and development of diseases, especially malignant tumors. Its high throughput and low cost advantages enable researchers to explore the pathogenic genes of diseases, and screen potential molecular markers and therapeutic targets from the level of genomics., Methods: This study collected the primary tumor tissues, matched paracancerous, normal tissues, and liver metastases of 4 CRC patients admitted to the Department of General Surgery of the First Affiliated Hospital of Soochow University, and performed high-depth whole-exome sequencing, with the sequencing depth of each sample reaching 123× on average, then filtered the sequencing data, compared them, and analyzed the bioinformatics data., Results: we found 8,565 single nucleotide variants (SNV) and 429 insertions/deletions (InDel) in the primary and hepatic lesion tissues, and the genes with the highest mutation frequency were titin (TTN), obscurin (OBSCN), and homeodomain-interacting protein kinase 2 (HIPK2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the mutant genes was conducted, and it was found that the mutant genes were mainly concentrated in the cells, cell parts, and cellular process of GO. The results of KEGG pathway analysis showed that mutations were mainly distributed in circadian entrainment, insulin secretion, and glutamatergic synapse. Further, we identified 723 SNV and Indel genes with high frequency mutations including TTN, OBSCN, and hydrocephalus-inducing protein homolog (HYDIN) across all tissues of liver metastases. The GO analysis showed that the mutated genes in liver metastatic tissues were mainly concentrated in cell, cell part, and cellular process. The KEGG pathway analysis showed that high frequency mutation genes were focused on gastric acid secretion, bile secretion, and melanogenesis., Conclusions: This study found some candidate genes related to the occurrence of CRC and liver metastasis through whole-exome sequencing of relevant tissues in CRC patients with liver metastasis, which is expected to provide new markers and therapeutic targets for such patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-21-9). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

There is a continuing high demand to design effective sensors for the determination of heavy metal ions (HMIs) since they are hazardous to both human health and the environment. In this study, we reported a facile fluorescent sensor array for rapid discrimination of HMIs based on a single gold nanocluster (AuNC) probe. This AuNC probe was prepared by using 2-mercapto-1-methylimidazole (MMI) as a ligand and polyvinypyrrolidone (PVP) as a dispersing agent. The fluorescence emission of PVP/MMI-AuNC was observed to be closely related to the pH value of the aqueous solution, which displays yellow (λ max = 512 nm) and red (λ max = 700 nm) fluorescence at pH 12.0 and 6.0, respectively. Further experiments indicated that different HMIs can produce differential effects on the photoluminescence of PVP/MMI-AuNC and thus generate distinct fluorescent responses at 512 and 700 nm. On the basis of this phenomenon, a fluorescent sensor array based on the PVP/MMI-AuNC was then built by simply changing pH value in the sensor element. A total of seven HMIs had their unique response patterns and were successfully distinguished by hierarchical cluster analysis and linear discriminant analysis both in buffer solution and spiked water samples, achieving 100% identification accuracy. This study provides a simple and powerful fingerprinting sensing platform for multiple HMIs, showing broad application prospects in the field of environmental monitoring., (Copyright © 2020 Elsevier B.V. All rights reserved.)

With a rapid advancement of nanotechnology and the close integration of disciplines, research on nanozymes (nanomaterials with enzyme-like activities), is becoming an expeditiously developing field. In recent years, platinum group element (PGE)-based (Pt, Pd, Ru, Rh, Ir, and Os) nanozymes developed successively, have not only promoted the research of nanozymes but also expanded the biomedical applications of nanomaterials. Generally speaking, PGE-based nanozymes process high catalytic efficiency, specific surface area, stability, and other physical/chemical properties, which benefit for their applications in biosensing, biological medicine, biomedical imaging, and environmental protection. This paper will introduce the research progress of PGE-based nanozymes including their synthesis, characterization, enzyme-like activities, stability, biocompatibility, toxicity, and applications for biological detection and clinical relevance. Our emphasis is put on unfolding the roles of PGE-based nanozymes in biomedical applications and how they overcome the limitations. Last but not least, trends and future perspectives of PGE-based nanozymes in biomedical applications are also provided., (© 2021 IOP Publishing Ltd.)

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-Au 20 NCs 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-Au 20 NCs, 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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-O 2 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 (ΔA 450nm ) 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., (Copyright © 2020 He, Yang, Lin, Peng, Lin, Deng, Chen and Hong.)

In this study, a colorimetric sensing assay of isoniazid based on excellent oxidase-like activity of heparin sodium stabilized platinum nanoparticles (HS-PtNPs) has been demonstrated. The newly prepared HS-PtNPs exhibit a great dispersion with an average size distribution of 4.8 ± 0.6 nm, and maintain more than 90% catalytic activity under strong acid and alkali or long-term storage conditions, indicating a robust nanomaterial with attractive potential. The HS-PtNPs show distinct oxidase-like activity with an ultrahigh affinity (Km = 0.01012 mM) for 3, 3', 5, 5'-tetramethylbenzidine (TMB). More significantly, we found that the pyridine ring of isoniazid has a strong reductive hydrazyl substitution, which can compete with TMB for the catalytic site of HS-PtNPs resulting in a colorless solution. Accordingly, a colorimetric sensing of isoniazid was fabricated. A linear relationship for isoniazid was achieved in 2.5 × 10 -6 to 2.5 × 10 -4  M (R 2  = 0.998) with a low limit of detection 1.7 × 10 -6  M (S/N = 3). Recovery experiments in drug tablets show that the standard recovery rates were 95%-103%. The quantitative detection data for isoniazid in drug tablets calculated respectively from the standard method and this method exhibited a high correlation coefficient (a slope of 0.9995), suggesting that high accuracy in isoniazid detection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 O 2 (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., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Protein-supported nanoparticles have a great significance in scientific and nanotechnology research because of their "green" process, low cost-in-use, good biocompatibility, and some interesting properties. Ruthenium oxide nanoparticles (RuO 2 NPs) have been considered to be an important member in nanotechnology research. However, the biosynthetic approach of RuO 2 NPs is relatively few compared to those of other nanoparticles. To address this challenge, this work presented a new way for RuO 2 NP synthesis (BSA-RuO 2 NPs) supported by bovine serum albumin (BSA). BSA-RuO 2 NPs are confirmed to exert peroxidase-like activity, electrocatalytic activity, in vitro salt resistance (2 M NaCl), and biocompatibility. Results indicate that BSA-RuO 2 NPs have higher affinity binding for 3,3',5,5'-tetramethylbenzidine or H 2 O 2 than bare RuO 2 NPs. Moreover, BSA turns out to be a crucial factor in promoting the stability of RuO 2 NPs. Taking the advantages of these improved properties, we established colorimetric (linear range from 2 to 800 μM, a limit of detection of 1.8 μM) and electrochemical (linear range from 0.4 to 3850 μM, a limit of detection of 0.18 μM) biosensors for monitoring in situ H 2 O 2 secretion from living MCF-7 cells. Herein, this work offers a new biosynthesis strategy to obtain BSA-RuO 2 NPs and sheds light on the sensitive biosensors to monitor the H 2 O 2 secreted from living cells for promising applications in the fields of nanotechnology, biology, biosensors, and medicine.

Donor-linker-acceptor (D-L-A)-based photoinduced electron transfer (PET) has been frequently used for the construction of versatile fluorescent chemo/biosensors. However, sophisticated and tedious processes are generally required for the synthesis of these probes, which leads to poor design flexibility. In this work, by exploiting a Schiff base as a linker unit, a covalently bound D-L-A system was established and subsequently utilized for the development of a PET sensor. Cysteamine (Cys) and N-acetyl-l-cysteine (NAC) costabilized gold nanoclusters (Cys/NAC-AuNCs) were synthesized and adopted as an electron acceptor, and pyridoxal phosphate (PLP) was selected as an electron donor. PLP can form a Schiff base (an aldimine) with the primary amino group of Cys/NAC-AuNC through its aldehyde group and thereby suppresses the fluorescence of Cys/NAC-AuNC. The Rehm-Weller formula results and a HOMO-LUMO orbital study revealed that a reductive PET mechanism is responsible for the observed fluorescence quenching. Since the pyridoxal (PL) produced by the acid phosphatase (ACP)-catalyzed cleavage of PLP has a weak interaction with Cys/NAC-AuNC, a novel turn-on fluorescent method for selective detection of ACP was successfully realized. To the best of our knowledge, this is the first example of the development of a covalently bound D-L-A system for fluorescent PET sensing of enzyme activity based on AuNC nanoprobes using a Schiff base.

A visual assay for the detection of heparinase was developed on the basis of a ternary system of Hg 2+ -heparin-osmium nanoparticles (OsNPs). First, heparin-capped OsNPs (heparin-OsNPs) were synthesized by a facile reduction method using heparin as the protecting/stabilizing agent. The oxidase-like activity of heparin-OsNPs, however, turned out to be low, which somewhat limits their application. We discovered that Hg 2+ can significantly/specifically boost the oxidase-like activity of heparin-OsNPs via electrostatic interaction. The oxidase-like activity of heparin-OsNPs toward the oxidation of the substrate, 3,3',5,5'-tetramethylbenzidine, by dissolved O 2 was found to increase by 76-fold in the presence of Hg 2+ . More significantly, heparin in heparin-OsNPs could be specifically hydrolyzed into small fragments in the presence of heparinase, which resulted in the weakening of the oxidase-like activity of Hg 2+ /heparin-OsNPs. On the basis of these findings, a linear response of the sensor for heparinase was obtained in the range 20-1000 μg/L with a low detection limit (15 μg/L), which is comparable to those of other reported sensors. Further, the colorimetric sensor was employed for the detection of heparinase in human serum samples with satisfactory results. We speculate that combining such surface modification of the osmium nanozyme with a sensing element could be an interesting direction for promoting nanozyme research in medical diagnosis.

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 H 2 O 2 -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.

Although numerous sensors have been successfully fabricated for the detection of various heavy metal ions by employing fluorescent gold nanoclusters (AuNCs) as nanoprobes, serious cross-interference often occurs when these ions coexist in samples, which results in glaring errors in quantification. In this study, glutathione-protected AuNCs (GSH-AuNCs) were synthesized and found to respond to both Cu 2+ and Hg 2+ via fluorescence suppression. Intriguingly, addition of Ag + to GSH-AuNCs could completely inhibit the quenching effect of Hg 2+ while not affecting the Cu 2+ -mediated quenching process. Ag + can combine with Au + on the surface of AuNCs to form a strong Ag + -Au + metallic bond, which disrupts the interaction between Hg 2+ and Au + and thus eliminates the corresponding quenching effect. Based on this phenomenon, a simple sensing approach for highly selective and sensitive detection of Cu 2+ in aqueous solution was developed using the GSH-AuNC/Ag + complex as a fluorescent turn-off nanoprobe. The proposed method exhibited good linearity in the concentration range 0.02-10 μM with a limit of detection of 12 nM. This assay was demonstrated to be suitable for determination of Cu 2+ in real water samples even in the presence of Hg 2+ , showing great promise as a tool for assessment of environmental security and drinking water quality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Platinum nanoparticles (Pt NPs) covered with a bovine serum albumin scaffold and a particle size of 1.5 nm (BSA-Pt S NPs) are shown to display enhanced multiple enzyme-mimicking activities including peroxidase, oxidase, and catalase-like activities. The peroxidase-like activity is characterized by robustness and low signal background. BSA-Pt S NPs were used to design colorimetric assays for H 2 O 2 and glucose. H 2 O 2 latter reacts with 3,3',5,5'-tetramethylbenzidine in the presence of BSA-Pt S NPs to form a blue product with an absorption maximum at 652 nm. The assay works in the 5-250 μM H 2 O 2 concentration range. The glucose assay is based on its glucose oxidase-catalyzed oxidation to produce gluconic acid and H 2 O 2 which then is colorimetrically quantified. Response is linear in the 10-120 μM glucose concentration range, and the detection limit is 2 μM (at S/N = 3). The method correlates well with the glucose standard method (R 2  = 0.997 in the 95% confidence interval) which confirms that glucose in human serum has been successfully detected. Graphical abstractImproved enzymatic assay for hydrogen peroxide and glucose by exploiting the enzyme-mimicking properties of BSA-coated platinum nanoparticles.

Few-atom gold nanoclusters (AuNCs) have been fabricated and used for various fields owing to their remarkable optical and photophysical features. However, the rational design for the antibody-mediated synthesis of fluorescent AuNCs for direct antigen-antibody reactions remains unexplored. In this work, immunoglobulin G (IgG)-functionalized AuNCs (IgG-AuNCs) were successfully prepared via a facile and fast biomineralization process. The generated IgG-AuNCs can emit intense red fluorescence with a high photoluminescence quantum yield. Besides strong emission, the bioactivity of IgG on the IgG-AuNCs can be retained. Surface plasmon resonance measurements suggested that IgG-AuNCs can bind to goat anti-human IgG with an affinity constant of 6.21 × 10 -8 M. A simple detection method was then developed using a dot-blot immunoassay with IgG-AuNCs as fluorescent tags. Experimental results confirmed that the IgG-AuNC-based fluorescent reporters had many advantages such as low nonspecific adsorption and good photostability, offering immense potential for the development of efficient biosensors. This work can be extended to other specific antibodies to produce multifunctional AuNCs and utilized to detect and monitor targeted analytes and biological events of interest.

It is found that catechol inhibits the oxidase-mimicking activity of chitosan-protected platinum nanoparticles (Chit-PtNPs) by competing with the substrate for the active site of the Ch-PtNPs. The inhibition mechanism of catechol is different from that of ascorbic acid in that it neither reacts with O 2 •- nor reduces the oxidized 3,3',5,5'-tetramethylbenzidine (TMB). Tyrosinase (TYRase) catalyzes the oxidation of catechol, thus restoring the activity of oxidase-mimicking Chit-PtNPs. By combining the Chit-PtNP, catechol, and TYRase interactions with the oxidation of TMB to form a yellow diamine (maximal absorbance at 450 nm), a colorimetric analytical method was developed for TYRase determination and inhibitor screening. The assay works in the 0.5 to 2.5 U·mL -1 TYRase activity range, and the limit of detection is 0.5 U·mL -1 . In our perception, this new assay represents a powerful approach for determination of TYRase activity in biological samples. Graphical abstract Schematic representation of a colorimetric method for tyrosinase (TYRase) detection and inhibitor screening. It is based on the fact that catechol can inhibit the oxidase-like activity of chitosan-stabilized platinum nanoparticles (Ch-PtNPs) by competing with the substrate for the active sites and TYRase can catalyze the oxidation of catechol.

Background: Most colorectal cancer (CRC) patients are diagnosed at an advanced or metastatic stage with poor prognosis. Ubiquitin-specific protease 6 N-terminal-like protein (USP6NL) with high expression in CRC tissues regulates CRC cell proliferation via Wnt/β-catenin pathway. We hypothesized that USP6NL impacts CRC growth and inhibition of USP6NL may be a novel treatment strategy to improve CRC therapy., Methods: USP6NL level in human CRC tissues and its association with tumor growth and metastasis were examined. Its roles and potential mechanisms in regulating tumor growth were studied by genetic and pharmacological manipulation of CRC cells in vitro and in vivo., Results: Herein, we found that USP6NL was up-regulated in tumorous tissues of CRC patients. Our data suggested that knockdown of USP6NL in human CRC cell lines (HCT116 and LOVO cells) inhibited cell proliferation, induced G0/G1 cell cycle arrest, and prevented the tumorigenicity of HCT116 cells in nude mice, and which was associated with the prevention of Wnt/β-catenin pathway. On the contrary, USP6NL overexpression in human CRC cells (SW480) showed the opposite result. Our data suggested that the promoted cell proliferation, G1/S cell cycle progression, and the enhanced expression of β-catenin Cyclin D1 and C-myc while reduced P27 induced by the overexpression of USP6NL were significantly reversed by additional treatment of XAV939, indicating that activating Wnt/β-catenin pathway was the mechanism, by which USP6NL exerted carcinogenesis in CRC in vitro. Besides, our data suggested that knockdown of USP6NL increased the ubiquitination of β-catenin, indicating that USP6NL may serve as a deubiquitinase that regulated β-catenin accumulation in this process. Furthermore, 10058-F4 down-regulated USP6NL, inhibited CRC cell proliferation and induced cell cycle arrest. The result demonstrated a possible feedback loop between USP6NL, β-catenin and C-myc in regulating CRC cell growth., Conclusion: USP6NL was an oncogene in CRC, and it may be a potential target for the treatment of CRC., Competing Interests: The authors declare that they have no competing interests.

Although it has been demonstrated that rare-earth elements (REEs) disturb and alter the catalytic activity of numerous natural enzymes, their effects on nanomaterial-based artificial enzymes (nanozymes) have been seldom explored. In this work, the influence of REEs on the peroxidase-like activity of bare gold nanoparticles (GNPs) is investigated for the first time, and a new type of Ce 3+ -activated peroxidase mimetic activity of GNPs is obtained. The introduced Ce 3+ can be bound to the bare GNP surface rapidly through electrostatic attraction, after which it donates its electron to the bare GNP. As H 2 O 2 is a good electron scavenger, more • OH radicals are generated on the surfaces of the bare GNPs, which can considerably enhance TMB oxidation. Due to its redox cycling ability, the activation effect of Ce 3+ is proved to be more efficient in comparison to those of the other reported metal ion activators (e.g., Bi 3+ , Hg 2+ , and Pb 2+ ). In addition, it is determined that Ce 3+ should directly contact with the gold core to trigger its activation effect. When the surface states of the bare GNPs are altered, the Ce 3+ -stimulated effect is strongly inhibited. Furthermore, a novel colorimetric method for Ce 3+ is developed, on the basis of its enhancing effect on the peroxidase mimetic activity of bare GNPs. The sensitivity of this newly developed method for Ce 3+ is excellent with a limit of detection as low as 2.2 nM. This study not only provides an effective GNP-based peroxidase mimic but also contributes in realizing new applications for nanozymes.

In this study, on the basis of the biomineralization capability of urease, a facile, one-step, and green synthetic method has been proposed for the fabrication of gold nanoclusters (AuNCs). The prepared urease-encapsulated AuNCs (U-AuNCs) exhibited strong red fluorescence emission (λ em = 630 nm) with a quantum yield as high as 17%. Interestingly, at a low concentration, the U-AuNC solution was found to be a dual-emissive system with the blue emission of the dityrosine (diTyr) residues of urease and the red emission of the embedded AuNCs. Further experiments demonstrated that p-nitrophenol (PNP) can selectively suppress the 410 nm emission of the diTyr residues of U-AuNCs without affecting the red emission of the U-AuNCs. The fluorescence quenching mechanism between U-AuNCs and PNP was systematically studied, and the leading role of the inner filter effect (IFE) was identified. Additionally, based on the sulfatase-catalyzed hydrolysis of p-nitrophenyl sulfate (PNPS) to release PNP, a self-referenced ratiometric detection method for sulfatase, which plays a crucial role in sulfur cycling, degradation of sulfated glycosaminoglycans and glycolipids, and extracellular remodeling of sulfated glycosaminoglycans, was developed by using dual-emissive U-AuNCs as the signal readout, in which the diTyr residues served as the probe and the AuNCs functioned as the internal reference. This IFE-based ratiometric sensing strategy showed a good linear relationship over the range of 0.01-1 U/mL ( R 2 = 0.997). The detection limit for sulfatase activity was 0.01 U/mL. The developed protocol was successfully used to detect sulfatase activity in human serum samples. The simplicity, rapidity, low cost, high credibility, good reproducibility, and excellent selectivity of the detection platform serve as an inspiration for further applications of fluorescent AuNCs in chemo/biosensing.

Background: Previous studies suggested that visual evoked potential (VEP) was impaired in patients with Parkinson's disease (PD), but the results were inconsistent., Methods: We conducted a systematic review and meta-analysis to explore whether the VEP was significantly different between PD patients and healthy controls. Case-control studies of PD were selected through an electronic search of the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. We calculated the pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs) between individuals with PD and controls using the random-effects model., Results: Twenty case-control studies which met our inclusion criteria were included in the final meta-analysis. We found that the P100 latency in PD was significantly higher compared with healthy controls (pooled WMD = 6.04, 95% CI: 2.73 to 9.35, P =0.0003, n =20). However, the difference in the mean amplitude of P100 was not significant between the two groups (pooled WMD = 0.64, 95% CI: -0.06 to 1.33, P =0.07) based on 10 studies with the P100 amplitude values available., Conclusions: The higher P100 latency of VEP was observed in PD patients, relative to healthy controls. Our findings suggest that electrophysiological changes and functional defect in the visual pathway of PD patients are important to our understanding of the pathophysiology of visual involvement in PD.

Objective: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Emerging evidence has verified that Rab1A plays an oncogenic role in several human malignancies including breast cancer, lung cancer, and hepatocellular carcinomas. However, the clinical significance and prognostic impact of Rab1A in CRC is still unclear., Patients and Methods: We initiated our investigation by immunohistochemistry and Western blot analysis to confirm Rab1A expression in CRC tissues. Meanwhile, the correlation of Rab1A expression and clinicopathologic features, as well as outcome in CRC patients, were retrospectively analyzed., Results: In the issue, Rab1A is overexpressed in CRC tissues compared with matched noncancerous tissues. Meanwhile, high Rab1A expression was significantly associated with the TNM stage, lymph node metastasis, and peritoneal metastasis. In addition, multivariate analyses identified Rab1A expression and TNM stage as independent predictors for CRC patients. Moreover, Kaplan-Meier survival analysis showed that patients with high Rab1A expression had a significantly worse survival time than those with low Rab1A expression, which especially affected the survival in CRC patients with advanced stage. Spearman analysis suggested that there was a positive relationship between Rab1A expression and preoperative serum carcinoembryonic antigen (CEA) for CRC patients., Conclusions: These results suggested that Rab1A is an important diagnostic marker for CRC, and Rab1A can be used as a valuable biomarker for prognosis as well as peritoneal metastasis in CRC patients. Rab1A may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

Dysregulation of SUMO-specific protease 1 (SENP1) expression has been reported in several kinds of cancer, including human colorectal and prostate cancers, proposing SENP1 as an oncogene with a critical role in cancer progression. miR-133a-3p has been reported as a tumor suppressor in several malignant neoplasias. However, the precise molecular mechanisms underlying its role in colorectal cancer remain largely unknown. The aim of this work was to investigate the relationship between miR-133a-3p and SENP1 in colorectal cancer cells. We found that miR-133a-3p expression was downregulated in colorectal cancer tissues. In silico analyses indicated that SENP1 is one of the target genes of miR-133a-3p. Overexpression of miR-133a-3p mimics was able to inhibit cell growth with G1 arrest of colorectal cancer cells. Overexpression of miR-133a-3p antisense promoted cell growth of colorectal cancer cells. The luciferase reporter experiments showed that miR-133a-3p regulated the expression of SENP1 by combining with its 3'-UTR and resulted in downregulation of SENP1 and upregulation of CDK inhibitors such as p16, p19, p21, and p27. These results suggest that the miR-133a-3p-SENP1 axis might play a role in cell proliferation and cell cycle regulation of colorectal cancer cells.

Biological denitrification is now one of the most widely applied techniques to remove nitrogen from the aquatic environment, and mixotrophic denitrification has gained attention as it takes the characteristics of both heterotrophic and autotrophic denitrification. This study investigated the biological denitrification efficiency and the bacterial community structure of sludge sampled from a mixotrophic denitrification reactor, before and after adding a certain amount of phosphate. The results showed that the bacteria have the capability of denitrification even without phosphorus, but the addition of phosphorus could significantly improve the biomass and the denitrification activity. After phosphate was added, the autotrophic and heterotrophic denitrification activity increased to 0.056 mg·(L·min·g) -1 and 0.232 mg·(L·min·g) -1 on N/VSS, which was 2.9 and 3.9 times that of the sludge activity before phosphorus addition, respectively. The bacterial community structure illustrated that the denitrifiers increased remarkably from 13.47% to 44.82% and that the dominate bacteria have also changed. Meanwhile, the growth of autotrophic, heterotrophic, and mixtrophic bacteria were all improved significantly after phosphorus was added.

Objectives: To investigate the clinical effect of the arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia., Methods: Data of twenty-six cases accepted arytenoid cartilage reposition under intravenous general anesthesia were analyzed, nineteen cases accepted laryngeal CT scan and cricoarytenoid joint reconstruction, all patients underwent endolaryngeal muscle electromyography examination. According to the position of cartilage dislocation prompted by laryngoscope and CT, the arytenoid cartilage was repositoned under the visual laryngoscope using special snake mouth reduction forceps. If bilateral arytenoid cartilage were still asymmetrically at the end of the surgery, patients needed repeated reposition 1 to 2 times 1 week after operation. The efficacy was evaluated 4 weeks later., Results: All patients had a hoarse and breathing voice preoperative. Under laryngoscope, there were different degrees of vocal cord movement disorders accompanied by incomplete glottis closure, 22 cases happened in left side and 4 in right side. The arytenoid cartilage was dislocated anteromedially in 25 cases and posterolaterally in 1 case. CT showed that 15 cases of arytenoid cartilage were tilted anteromedially; the interval of the cricoarytenoid joint was widened. In axial CT images, there were no direct signs of the arytenoid cartilage dislocation in the 4 cases, but the abnormal position was seen in the reconstruction images. The laryngeal electromyography indicated that 7 cases were abnormal, duration of motor unit potential were visible and the raising potential were mixed. There were 4 patients with normal voice in the first day after surgery, and 19 cases underwent twice and 3 cases underwent three times surgery. Vioce became normal in 4 weeks. Swallowing pain and bucking were all disappeared. Vocal cords movement were recovered to normal level in 25 cases. In 1 case with neck strangulation, the vocal cord movement was slightly worse than health side, but significantly better than that before operation., Conclusions: The arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia was an effective method for the treatment of the cricoary-tenoid joint dislocation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To investigate the significance of circulating tumor cells (CTC) in squamous cell carcinoma of the head and neck (HNSCC). Methods: Twenty-four patients with HNSCC treated between October 2016 and July 2017 in our department were selected (experimental group), including 23 males and 1 females, aged 47-81 years. There were 14 cases of squamous cell carcinoma of larynx and 10 cases of hypopharynx, including I-Ⅱ stage (5 cases) and Ⅲ- Ⅳ stage (19 cases). All patients were primary and/or relapsed after treatment. Nine healthy volunteers were selected as control group. A novel in vivo capture technique (CellCellector system) was used to detect CTC. SPSS23.0 was used for statistical analysis. Results: The total capture rate of CTC in patients with HNSCC before treatment was 70.8% (17/24), with 40% (2/5) for patients at I-Ⅱ stage, and 78.9% (15/19) for patients at Ⅲ- Ⅳ stage, and was 0 in patients of control group. The total capture rate of CTC in patients with HNSCC after treatment was 50% (8/16). There was no significant correlation between CTC and age, sex, location of tumor or lymph node metastasis ( P >0.05). CTC was related to tumor staging and tumor differentiation ( P <0.05). The positive rate of EGFRVⅢ in CTC was 26.3% (5/19). Conclusions: The CellCollector system is a very efficient way of detecting CTC, and CTC plays an important role in the occurrence, progression and metastasis of HNSCC.

Abscisic acid (ABA) plays pivotal roles in plant growth and development and in responses to diverse stresses. It also modulates the growth of primary and lateral roots. Much evidence indicated that key cellular components auxin, ethylene, PLETHs, reactive oxygen species and Ca 2+ are involved in the regulation of ABA suppression of root elongation. In this review, we summary the molecular mechanism for ABA inhibiting primary root growth, focusing on the roles of these components in Arabidopsis.

This study was carried out to investigate the possibility of a thiosulfate-driven autotrophic denitrification for nitrate-N removal from micro-polluted surface water. The aim was to study the effects of [Formula: see text] ratio (S/N molar ratio) and hydraulic retention time (HRT) on the autotrophic denitrification performance. Besides, utilization efficiencies of [Formula: see text] along the biofilter and the restart-up of the bioreactor were also investigated. Autotrophic denitrification using thiosulfate as an electron donor for treating micro-polluted surface water without the addition of external alkalinity proved to be feasible and the biofilter could be readied in two weeks. Average nitrate-N removal efficiencies at HRTs of 0.5, 1 and 2 h were 78.7%, 87.8% and 97.4%, respectively, and corresponding removal rates were 186.24, 103.92 and 58.56 g [Formula: see text], respectively. When water temperature was in the range of 8-12°C and HRT was 1 h, average nitrate-N removal efficiencies of 41.9%, 97.1% and 97.0%, nitrite accumulation concentrations of 1.45, 0.46 and 0.22 mg/L and thiosulfate utilization efficiencies of 100%, 98.8% and 92.1% were obtained at S/N ratios of 1.0, 1.2 and 1.5, respectively. Besides, the autotrophic denitrification rate in the filtration media layer was the highest along the biofilter at an S/N ratio of 1.5. Finally, after a one-month period of starvation, the biofilter could be restarted successfully in three weeks without inoculation of seed sludge.

Objective: It has been well-established that microRNAs (miRNAs), a class of short non-coding RNA molecules, play an important role in the development of gastric cancer. In the present study, we focused on miR-105, a novel miRNA not previously linked to gastric cancer., Patients and Methods: 36 paired surgically resected gastric cancer tissues and matched adjacent normal tissues were used to detect the expression of miR-105. AGS cells were used to overexpress or silence of miR-105 and to determine its effect on several tumorigenic properties. A cell proliferation enzyme-linked immunosorbent assay was used to analyze the incorporation of BrdU during DNA synthesis of AGS cells. Total cDNA from AGS cells was used to amplify the 3'-UTR of YY1 by PCR and luciferase activity was determined using the Dual-Luciferase Reporter Assay System RESULTS: We found that expression of miR-105 was reduced in gastric cancer tissues, compared with adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-105 suppressed, whereas its inhibition promoted cell viability and proliferation. We further identified Yin Yang 1 (YY1) as a direct target of miR-105, by which miR-105 exerted its anti-proliferative role. Moreover, we found that DNMT3A was responsible for the down-regulation of miR-105 in gastric cancer cells., Conclusions: Our data demonstrate that miR-105 inhibits gastric cancer cell proliferation and progression, which might provide a therapeutical target for cancer therapy.

Objective: This paper discusses the expression and significance of CD4⁺CD25⁺ Tregs and Foxp3 in peripheral blood of patients with head and neck squamous cell carcinoma. Method: We have collected 40 cases of head and neck squamous cell carcinoma patients with newly diagnosed or relapse after treatment, all of them underwent surgery, 39 males and 1 females, aged 41-79 years, in our department from January 2014 to December 2015. At the same time, 10 healthy volunteers are enrolled as control group. 2 ml peripheral blood has been detected by flow cytometry, and the ratio of CD4⁺CD25⁺/CD4⁺ and CD4⁺CD25⁺Fxop3⁺/CD4⁺ are calculated, respectively. SPSS 23.0 is used for statistical analysis. Result: CD4⁺CD25⁺ Tregs is highly expressed in head and neck tumors, compared with that in the healthy control, and the difference is statistically significant ( P <0.01). There is significant difference between the early and late stage ( P <0.05). The positive rate of Foxp3+ is higher in CD4⁺CD25⁺ Tregs positive cells than in control group ( P <0.01). The difference of positive rate between late stage and early stage head and neck tumors is statistically significant ( P <0.05). There is a significant positive correlation between CD4⁺CD25⁺ Tregs and Foxp3 ( r =0.95). Conclusion: CD4⁺CD25⁺ Tregs and Foxp3 are highly expressed in the peripheral blood of patients with head and neck squamous cell carcinoma. Through the inhibition of the immune system in patients with head and neck squamous cell carcinoma, the development of carcinoma were promoted., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)