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To conduct a comprehensive investigation of the sarcoma immune cell infiltration (ImmCI) patterns and tumoral microenvironment (TME). We utilized transcriptomic, clinical, and mutation data of sarcoma patients (training cohort) obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) server. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithms were applied to decipher the immune cell infiltration landscape and TME profiles of sarcomas. An unsupervised clustering method was utilized for classifying ImmCI clusters (initial clustering) and ImmCI-based differentially expressed gene-driven clusters (secondary clustering). Mortality rates and immune checkpoint gene levels was analyzed among the identified clusters. We calculated the ImmCI score through principal component analysis. The tumor immune dysfunction evaluation (TIDE) score was also employed to quantify immunotherapy efficacy between two ImmCI score groups. We further validated the biomarkers for ImmCI and gene-driven clusters via experimental verification and the accuracy of the ImmCI score in predicting survival outcomes and immunotherapy efficacy by external validation cohorts (testing cohort). We demonstrated that ImmCI cluster A and gene-driven cluster A, were beneficial prognostic biomarkers and indicators of immune checkpoint blockade response in sarcomas via in-silico and laboratory experiments. Additionally, the ImmCI score exhibited independent prognostic significance and was predictive of immunotherapy response. Our research underscores the clinical significance of ImmCI scores in identifying sarcoma patients likely to respond to immunotherapy., Competing Interests: 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., (© 2024 The Authors.)

Microcin J25 (MccJ25), a lasso peptide antibiotic with a unique structure that resembles the lariat knot, has been a topic of intense interest since its discovery in 1992. The precursor (McjA) contains a leader and a core segment. McjB is a protease activated upon binding to the leader, and McjC converts the core segment into the mature MccJ25. Previous studies suggested that these biosynthetic steps likely proceed in a (nearly) concerted fashion; however, there is only limited information regarding the structural and molecular intricacies of MccJ25 biosynthesis. To close this knowledge gap, we used AlphaFold2 to predict the structure of the precursor (McjA) in complex with its biosynthetic enzymes (McjB and McjC) and queried the critical predicted features by protein engineering. Based on the predicted structure, we designed protein variants to show that McjB can still be functional and form a proficient biosynthetic complex with McjC when its recognition and protease domains were circularly permutated or split into separate proteins. Specific residues important for McjA recognition were also identified, which permitted us to pinpoint a compensatory mutation (McjB M108T ) to restore McjA/McjB interaction that rescued an otherwise nearly nonproductive precursor variant (McjA T-2M ). Studies of McjA, McjB, and McjC have long been mired by them being extremely difficult to handle experimentally, and our results suggest that the AF2 predicted ternary complex structure may serve as a reasonable starting point for understanding MccJ25 biosynthesis. The prediction-validation workflow presented herein combined artificial intelligence and laboratory experiments constructively to gain new insights.

A cortisol biosensor was developed based on double-conducting polymer nanowires, which exhibits excellent conductivity, resistance to biological contamination, and outstanding sensing performance. The biosensor employs dual-mode electrochemical techniques, namely, differential pulse voltammetry (DPV) and chronoamperometry (CA), for the sensitive and low fouling detection of the glucocorticoid hormone cortisol. Experimental results demonstrated that the linear detection range of the biosensor in DPV mode was 1.0 × 10 -14 -1.0 × 10 -8  M, with a detection limit of 0.131 × 10 -14  M. In CA mode, the biosensor exhibited a detection range of 1.0 × 10 -13 -1.0 × 10 -7  M and a detection limit of 0.313 × 10 -13  M. The biosensor was successfully utilized for the rapid detection of cortisol in human saliva. The combination of a high-specificity cortisol aptamer and functionalized double-conducting polymer nanowires ensured the exceptional specificity and sensitivity of the biosensor in detecting real biological samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

MicroRNA, as a distinctive biomarker, plays a crucial role in the early prognosis and diagnosis of numerous severe diseases. However, due to its inherent properties such as low abundance, small size, and high sequence similarity, the sensitive and accurate detection of microRNA remains a major challenge. Herein, a dual-mode electrochemical biosensing platform was developed for microRNA detection, based on poly(3,4-ethylenedioxythiophene) (PEDOT) doped with graphene oxide-Fe 3 O 4 (GO-Fe 3 O 4 ) nanocomposite. The GO-Fe 3 O 4 /PEDOT composite demonstrated a porous microstructure, outstanding conductivity, and robust catalytic activity towards nitrite. It was electrodeposited onto the electrode surface in a one-step process using the cyclic voltammetry method (CV). The microRNA biosensor was obtained by anchoring DNA with amino groups to the GO-Fe 3 O 4 /PEDOT layer through the formation of amide bonds. The designed dual-mode microRNA biosensor demonstrated a broad linear range spanning from 10 -15 M to 10 -6 M, with low detection limits of 5.18 × 10 -15 M and 7.36 × 10 -15 M when using chronocoulometry (CC) and amperometric i-t curve (i-t) modes, respectively. Furthermore, a dual-mode electrochemical biosensor has been successfully developed and utilized for the detection of microRNA in human serum, demonstrating its potential for precise and sensitive microRNA detection and its practical application value in clinical medicine., 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. Published by Elsevier B.V.)

Background: The adenosine triphosphate-binding-cassette (ABC) transporter orchestrates the transmembrane transport of diverse substrates with the aid of ATP as an energy source. ABC transporter constitutes a widespread superfamily of transporters prominently present on the cellular membrane of organisms. Advancements in understanding have unveiled additional roles beyond mere intracellular or extracellular transport functions for the ABC protein family, encompassing involvement in DNA repair, protein translation, and gene expression regulation. Yet its role in tumors is still unknown., Methods: This study drew support from multiple databases, including Gene Expression Omnibus (GEO), European Genome-phenome Archive (EGA), The Cancer Genome Atlas (TCGA), and employed multidimensional bioinformatics analyses, incorporating online databases and the R-project. Through a comprehensive analysis, we seek to discern transcriptional-level disparities among genes and their consequential impacts on prognosis, tumor microenvironment (TME), stemness score, immune subtypes, clinical characteristics, and drug sensitivity across human cancers., Results: ABC transporter subfamily B (ABCB) family genes exhibited heightened expression across diverse tumors, demonstrating a significant correlation with overall prognosis in pan-cancer contexts. Notably, gene expression levels manifested substantial associations with TME, stemness score, immune subtypes, clinical characteristics, and drug sensitivity in specific cancers, including kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD). Within this subset, transporter associated with antigen processing 1 ( TAP1 ), TAP2 , and ABCB6 emerged as noteworthy oncogenes., Conclusions: The outcomes of this study contribute to a comprehensive understanding of the implications of ABCB family genes in tumor progression, offering insights into potential therapeutic targets for cancer. Notably, the identification of ABCB6 as a significant oncogene suggests promising avenues for targeted therapies in KIRP, LIHC, and PAAD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2050/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Background: Arrhythmogenic ventricular cardiomyopathy (AVC) is a common cause of ventricular arrhythmias and mortality, but limited data are available from large Asian cohorts. Our aim was to explore the current status of AVC and second, we examined the prevalence of ventricular tachycardia (VT), heart failure (HF) and mortality in patients with AVC in the Chinese population., Hypothesis: At present, some studies have reported that the incidence of AVC is on the rise, which may be due to the increasing number of diagnostic methods for AVC. However, there is no epidemiological data on AVC in the Chinese population, so we speculate that the incidence of AVC in the Chinese population is increasing., Methods and Results: We studied 15 888 adults from the Beijing Municipal Health Commission Information Center (BMHCIC) registry database in China from January 2010 to December 2020, and calculated the average annual percentage change (AAPC). Second, we determined the incidence of VT, HF and mortality in patients with AVC. Of the 10 318 men and 5570 women who were screened by cardiac magnetic resonance or examined by myocardial biopsy, there were a total of 256 newly diagnosed AVC patients (mean [SD]: 37.54[17.10]; 39.45% female). The incidence of AVC increased from 7.60 (3.12-12.06) in 2010 to 19.62 (11.51-27.75) per 1000 person-years in 2020. Males had higher incidence of AVC than females. The AAPC for the rising incidence of AVC was 8.9 %. Males had similar VT prevalence (70.32% vs. 62.38%, p = 0.19) and mortality (1.94% vs. 1.98%, p = 0.98) but lower HF prevalence (42.58% vs. 60.40%, p = 0.006), when compared to females. Radiofrequency ablation (RFA) was more likely to be performed in males (p = 0.006)., Conclusions: The rising trend in AVC incidence was evident, with two-fold increase by 2020. Males with AVC had similar VT prevalence and mortality rate, but HF prevalence were lower than females, perhaps impacted by RFA use., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Due to its traditional fermentation, there are obvious limits on the quality improvements in black tea. However, microbial fermentation can provide an abundance of metabolites and improve the flavor of tea. The "golden flower" fungi are widely used in the microbial fermentation of tea and has unique uses in healthcare. To further explore the improvements in black tea quality achieved via microbial fermentation, we used widely targeted metabolomics and metagenomics analyses to investigate the changes in and effects of metabolites and other microorganisms during the interaction between the "golden flower" fungi and black tea. Five key flavor metabolites were detected, the levels of catechin, epigallocatechin gallate, (-)-epicatechin gallate were decreased by different degrees after the inoculation of the "golden flower" fungus, whereas the levels of caffeine and (+)-gallocatechin increased. Botryosphaeriaceae, Botryosphaeriales, Dothideomycetes, Aspergillaceae, Trichocomaceae, and Lecanoromycetes play a positive role in the black tea fermentation process after inoculation with the "golden flower" fungi. D-Ribose can prevent hypoxia-induced apoptosis in cardiac cells, and it shows a strong correlation with Botryosphaeriaceae and Botryosphaeriales. The interaction between microorganisms and metabolites is manifested in tryptophan metabolism, starch and sucrose metabolism, and amino sugar and nucleotide sugar metabolism. In conclusion, the changes in metabolites observed during the fermentation of black tea by "golden flower" fungi are beneficial to human health. This conclusion extends the knowledge of the interaction between the "golden flower" fungi and black tea, and it provides important information for improving the quality of black tea., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Shan, Li, Kong, Hou, Wu and Chen.)

An antifouling electrochemical biosensor was constructed based on chondroitin sulfate (CS)-functionalized polyaniline (CS/PANI) and DNA-peptide conjugates that is capable of assaying cortisol directly in human fluids. First, a CS-doped PANI nanocomposite (sensing substrate) was electrodeposited onto a bare glassy carbon electrode to promote electron transport, providing the sensing signal from high peak currents of PANI to improve the sensitivity of the biosensor. Dendritic DNA-peptide conjugates were assembled onto the CS/PANI by exploiting the highly specific and strong interactions between biotin and streptavidin, which amplified the sensing signals toward cortisol. The integration of the DNA-peptide conjugates into the CS/PANI nanocomposite ensured that the biosensor had a synergistic antifouling effect and was capable of detecting cortisol directly in body fluids (sweat, saliva, and tears). When assaying cortisol levels, the biosensor exhibited a linear range over the cortisol concentrations of 1 × 10 -12 -1 × 10 -7 M and a low limit of detection (0.333 × 10 -12 M). In the detection of cortisol in real samples, the relative standard deviation (RSD) of the biological samples ranged from 2.94 to 4.23%, and the recovery were calculated to be in the range 95.2-103.2%., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies., Methods: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations., Results: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery., Conclusion: Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.

Objectives: This study aims to develop and validate a prognostic signature based on 7-methylguanosine-related (M7G-related) miRNAs for predicting prognosis and immune implications in breast invasive carcinoma (BRCA)., Materials and Methods: M7G-related miRNA data of BRCA were obtained from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO)-penalized, univariate, and multivariate Cox regression analyses were used to construct the prognostic signature. Furthermore, the predictive validity was verified using Kaplan-Meier (KM) survival risk and receiver operating characteristic (ROC) plots. Internal random sampling verification was used to simplify and validate the signature. RT-qPCR was used to quantify the expression level of transcriptional profiles. The independent prognostic role of the risk score was validated using univariate and multivariate regression. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used for functional and immune enrichment analysis., Results: A total of 18 M7G-related miRNAs were identified to construct the prognostic signature in BRCA. The low-risk group exhibited significantly higher overall survival than the high-risk group in the KM survival plot (P < 0.001). The area under the curve (AUC) for 1-, 3-, and 5-year survivals in the ROC curve were 0.737, 0.724, and 0.702, respectively. The survival significance in the training and testing cohorts was confirmed by random sampling verification. The most prominent miRNAs in the signature were the miR-7, miR-139, miR-10b, and miR-4728. Furthermore, immune scores for B, mast, and Th1 cells varied between risk groups. Our research demonstrated that CD52 was the most positively correlated gene with immune cells and functions in BRCA., Conclusion: Our study presents a comprehensive and systematic analysis of M7G-related miRNAs to construct a prognostic signature in BRCA. The signature demonstrated excellent prognostic validity, with the risk score as an independent prognostic factor. These results provide critical evidence for further investigation of M7G miRNAs and offer new insights for BRCA patients in the context of effective immunotherapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: In this study, we assessed the effects of psychiatric issues and early enteral nutrition therapy on anxiety and quality-of-life of patients with gastric cancer. Methods: We enrolled 60 patients with gastric cancer treated from January 2018 to November 2020 and divided them into 2 groups using a random number table (N=30 per group). All patients received early enteral nutrition therapy. The control group was given routine nursing; treatment of persons in the observation group was supplemented with additional psychiatric nursing. We then compared anxiety-depression scores, treatment compliance, nutritional status indices, and quality-of-life score. Results: The Self-rating Anxiety Scale (SAS) score and the Self-rating Depression Scale (SDS) score significantly declined in both groups after nursing compared with those before nursing (p<.05). After nursing, the SAS score and SDS score were lower in the observation group versus the control group (p<.05). The total rate of treatment compliance in the observation group (93.33%) was higher than that in the control group (73.33%) (p<.05). After nursing, the levels of hemoglobin, albumin, prealbumin, and transferrin were significantly higher in both groups than before nursing (p<.05), but higher in the observation group (p<.05). After nursing, the quality-of-life score was significantly higher in both groups than before nursing (p<.05), but higher in the observation group (p<.05). Conclusion: During enteral nutrition therapy for patients with gastric cancer, psychiatric treatment can effectively alleviate patient anxiety and depression, enhance treatment compliance, improve nutritional status, and enhance quality-of-life.

Purpose: To evaluate the four measurement approaches on the determination of effective optical zone (EOZ) using Scheimpflug tomography after small-incision lenticule extraction surgery in eyes with high myopia., Setting: Corneal refractive surgery conducted in an eye hospital in southern China., Design: This is a retrospective cohort study., Methods: In total, 74 subjects were recruited. EOZ was measured at 3 months postoperatively using vertex-based (EOZ V ), pupil-based (EOZ P ), 4 mm-ring-based total corneal refraction method (EOZ 4 ) and tangential curvature difference map method (EOZ D ), and their consistencies were compared. EOZs and planned optical zone (POZ) were compared and analyzed with eccentricity, ablation degree (AD) and total corneal aberrations., Results: At 3 months after surgery, the mean root mean square of ΔHOA, ΔComa, ΔTrefoil and ΔSA were 0.53 ± 0.27 μm, 0.36 ± 0.20 μm, 0.01 ± 0.84 μm and 0.16 ± 0.14 μm, respectively. EOZ V , EOZ P , EOZ 4 and EOZ D were 5.87 ± 0.44 mm, 5.85 ± 0.45 mm, 4.78 ± 0.40 mm and 5.29 ± 0.27 mm, respectively, which were significantly smaller than POZ 6.48 ± 0.16 mm. Bland-Altman plots showed a good consistency among the four EOZs. The difference between the EOZ V and EOZ P was 0.02 mm within the range of clinically acceptable difference. In addition, the eccentricity was positively correlated with ΔHOA, ΔComa and ΔSA., Conclusions: All 4 measurement approaches demonstrated the reduction of EOZs compared to POZ. The EOZ V was the closest to POZ, followed by EOZ P . The ΔEOZs showed no significant difference with eccentricity, AD and corneal aberrations., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Dual-mode electrochemical aptasensor based on nitrogen-doped graphene (NG) doped with the conducting polymer polypyrrole (PPy) nanocomposite is proposed for the determination of acetamiprid. NG/PPy was electrodeposited onto the glassy carbon electrode (GCE) using cyclic voltammetry technique. NG/PPy/GCE showed outstanding electrocatalytic activity for the oxidation of nitrite due to "active region" induced by the charge redistribution of carbon atoms. The ultrasensitive dual-mode biosensor for acetamiprid could be easily developed by coupling acetamiprid aptamers with the NG/PPy hybrid. The specific binding between acetamiprid and the aptamers resulted in the increase of differential pulse voltammetry (DPV) signal change and the decrease of chronoamperometry (CA) signal, and the concentration of acetamiprid could be measured. The working potentials of DPV and CA were - 0.2 ~ 0.4 V and - 0.4 ~ 0.4 V (vs. SCE), respectively. The dual-mode acetamiprid biosensor showed a wide linear range from 10 -12 to 10 -7  g mL -1 , with low detection limits of 1.15 × 10 -13  g mL -1 and 7.32 × 10 -13  g mL -1 through DPV and CA modes, respectively. Moreover, owing to high active area and superior conductivity, as well as good electrocatalytic ability, the dual-sensing platform based on NG/PPy nanocomposite supported the quantification of acetamiprid in complex samples. A dual-mode electrochemical aptasensor based on NG/PPy nanocomposite for acetamiprid detection was proposed through both the increase of differential pulse voltammetry (DPV) signal change and the decrease of chronoamperometry (CA) signal of the nitrite oxidation electrocatalyzed by NG/PPyn in sensors and biosensors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Ordinary cement is not environmentally friendly, has high cost and lacks superior performance. Many scholars use various admixtures to adjust the properties of cement slurry, but admixtures are usually not environmentally friendly, and it is difficult to ensure that the properties after deployment meet engineering requirements. In this study, a variety of admixtures were obtained using the environmental protection method, and the optimal mixing ratio was analyzed by combining the entropy weight method and the Taguchi grey relational analysis method. The developed cement slurry was compared with conventional slurry from both macroscopic and microscopic aspects. Aiming at the problem that previous scholars lacked the engineering feasibility verification of the developed slurry, this study combined the constitutive equation regression analysis method, discrete element numerical simulation and other methods to study various actual engineering conditions. The results show that the optimal mix ratio of silica fume cement slurry has good permeability characteristics under the conditions of different roughness, grouting pressure and confining pressure. At the same time, under different geological temperatures and different erosive liquid states, the cement slurry stone body shows good properties of reinforcement materials., Competing Interests: The authors declare no conflict of interest.

Objective: Through analysis of ABO blood group gene typing technology, to assist in the identification of difficult clinical serological specimens., Methods: A total of 10 forwardreverse typing ambiguous samples were collected from January 2021 to August 2021 in our hospital.ABO genotypes were analysed by gene sequencing., Results: The genotypes of 10 ABO ambiguous blood group samples were A102/BW11, A102/BW12, O02/O02, A102/B303, A102/B101, BW11/O02, B101/O04, BW11/O01, BW11/O01, A101/O02, respectively. The genotype results of 6 cases was consistent with the serological phenotype, and the serological phenotype of 4 cases were different from the geno sequencing., Conclusion: ABO blood groups genotyping technology combined with serological typing can be used for accurate typing of ambiguous blood group, and better ensure the safety of blood transfusion.

The development of biosensors capable of averting biofouling and detecting biomarkers in complex biological media remains a challenge. Herein, an ultralow fouling and highly sensitive biosensor based on specifically designed antifouling peptides and a signal amplification strategy was designed for prostate specific antigen (PSA) detection in human serum. A low fouling layer of poly(ethylene glycol) (PEG) doped the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was electrodeposited on the electrode surface, followed by the immobilization of streptavidin and further attachment of biotin-labelled peptides. The peptide was designed to include PSA specific recognition domain (HSSKLQK) and antifouling domain (PPPPEKEKEKE), and the terminal of the peptide was functionalized with -SH group. DNA functionalized gold nanorods (DNA/AuNRs) were then attached to the electrode, and methylene blue (MB) molecules were adsorbed to the DNA to form the signal amplifier. In the presence of PSA, the peptide was specifically cleaved and resulted in the loss of AuNRs together with DNA and MB, and thus significant decrease of the current signal. The biosensor exhibited a low limit of detection (LOD) of 0.035 pg mL -1 (S/N = 3), with a wide linear range from 0.10 pg mL -1 to 10.0 ng mL -1 , and it was able to detect PSA in real human serum owing to the presence of the antifouling peptides, indicating great potential of the constructed biosensor for practical application., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The conducting polymer polypyrrole nanocones wrapped by metal cobalt (Co/PPy) are a promising platform for the detection of sodium nitrite, which can be obtained by an electrochemical deposition technique under a mild condition. Co/PPy nanocone arrays combined the high conductivity and large specific surface area of PPy nanocones with the redox properties of metal cobalt, and their 3D structure can provide more active sites for nitrite detection. Owing to the microstructure and excellent electrical properties of the nanocomposite, Co/PPy nanocone arrays were convenient to construct a high-performance nitrite sensor. The microscopic morphology and composition of Co/PPy nanocone arrays were characterized by SEM, FT-IR, XPS, and XRD, and their electrochemical performances were also investigated. The experimental results showed that Co/PPy nanocones exhibited excellent performance for nitrite determination. The sensors were used for the determination of nitrite in pickled Chinese cabbage and water samples, and the results were consistent with those of spectrophotometry. Hence, the synthesized Co/PPy nanocone arrays have a broad application prospect in food safety, environmental protection, and industrial manufacturing., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

A dual-sensing platform is proposed based on multi-walled carbon nanotubes/Prussian blue-functionalized polypyrrole nanowire array (PPY/MWCNTs/PB). Highly aligned PPY nanowire arrays were electrochemically prepared on the surface of glassy carbon electrodes, which were doped with MWCNTs/PB nanocomposites. The nanomaterial combines the characteristics of the PPY nanowires (high conductivity and large specific surface area) and MWCNTs/PB (excellent catalytic performance and intrinsic redox activity). Owing to the nanowire microstructure and outstanding electrical properties, the PPY/MWCNTs/PB nanowire arrays show excellent electrocatalysis of the reduction of hydrogen peroxide and facilitate the construction of a high-performance biosensing platform for microRNA (miRNA). A linear relationship between analytical signal and concentration of hydrogen peroxide and miRNA was obtained in the range 5 to 503 µM (1.4-5.1 mM) and 0.1 pM to 1 nM, and detection limits of 1.7 μM and 33.4 fM, respectively. This new supersensitive sensing platform has broad application prospects of biomolecule and other analyte determination in drug, biomedical, plant protection, and environmental analysis. Prussian blue/multi-walled carbon nanotubes functionalized polypyrrole nanowire arrays (PPY/MWCNTs/PB) were prepared by a facile one-step electrochemical method. PPY/MWCNTs/PB nanowire arrays show excellent electrocatalysis of the reduction of H 2 O 2 and facilitate the construction of a high-performance biosensing platform for microRNA.

The index of dominance ( S ), average crowding ( X * ), niche breadth ( B i ), and niche overlap ( Q ik ) of dominant zooplankton species were calculated using data collected from four zooplankton surveys from May 2016 to February 2017 in Yueqing Bay, Zhejiang Province. The results showed that there were 17 dominant zooplankton species (with S ＞0.02). The niche breadth values of those dominant species differed greatly and were positively correlated with S . The niche overlaps of zooplanktons were extremely low. The total amount of species pairs with niche overlap higher than 0.6 ( Q ik ＞0.6) were 25 in Yueqing Bay, which represented 18.4% of the total pairs. Results from the redundancy analysis showed that the distribution of dominant zooplankton species was mainly affected by temperature and salinity, which caused ecological differentiation of zooplankton species.

Ultrasensitive and low-fouling microRNA electrochemical biosensors were successfully constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. For the three kinds of antifouling materials investigated, the newly designed and synthesized peptide exhibited superior antifouling ability to others, and it could effectively reduce the nonspecific adsorption of proteins and even prevent the fouling effect of serum. Compared with microRNA biosensors without antifouling capability, or those modified with polyethylene glycol or mercapto alcohol, the biosensor modified with the designed zwitterionic peptide showed the highest specificity for single-base mismatch, three-base mismatch, and completely complementary microRNAs. Most interestingly, the experimental results indicated that the introduction of antifouling molecules to the sensing interfaces did not significantly change the sensitivity of the biosensor. The strategy of constructing antifouling biosensors based on newly synthesized zwitterionic peptides and conducting polymers can be promisingly extended to the development of other electrochemical sensors and biosensors without encountering biofouling. Graphical abstract Ultrasensitive and low-fouling microRNA electrochemical biosensors were constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. The biosensor modified with the designed zwitterionic peptide showed the highest specificity amongst four kinds of biosensors.

The application of polypeptides in bio-interfaces and biosensors is of great interest because polypeptides are biocompatible and easy to design. A novel polymer nanocomposite was prepared by the electropolymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) with a newly designed polypeptide. The nanocomposite polypeptide doped PEDOT (PEDOT/PEP), with a 3D microporous network structure, large surface area and excellent antifouling ability, was utilized for the attachment of BRCA1 complementary oligonucleotides to construct a DNA biosensor. The fabricated DNA biosensor showed favorable selectivity (with a detection limit of 0.0034 pM) and high sensitivity. The biosensor was also capable of detecting the target DNA (BRCA1) in 1% (V/V) human serum samples. The combination of a conducting polymer PEDOT with an antifouling and biocompatible polypeptide demonstrates a new method for preparing electrochemical sensors, that are capable of detecting targets in complex biological samples without strong nonspecific protein adsorption., 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.)

Biosensors have tremendous revolutionary potential for the precise location and rapid detection of biomarkers for human disease. However, the minimization of nonspecific protein adsorption interactions and surface contamination is critical for their application in complex media. We report herein, the antifouling interface was constructed by electrochemical copolymerization of poly (3,4-ethylenedloxythlophene) (PEDOT) and glycyrrhiza polysaccharide (GPS). Hydrophilic PEDOT/GPS can reduce the interference and nonspecific adsorption of biological protein macromolecules, which has been verified by electrochemical and fluorescent characterization. Gold nanoparticles (AuNPs) were subsequently modified onto PEDOT/GPS surface to attach biomacromolecules containing thiol groups. MicroRNA, the promising biomarker of a large numbers of genetic diseases, was used as the testing model. Due to the robust antifouling capability of PEDOT/GPS as well as high biocompatibility of GPS/AuNPs, the fabricated biosensor based on PEDOT/GPS/AuNPs demonstrated excellent sensing performance, such as a wide detection range (0.01 nM-10 nM), a low detection limit (300 fM) and high reproducibility, showing great potential of medical 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.)

Identifying patient-specific clonal IGH/TCR junctional sequences is critical for minimal residual disease (MRD) monitoring. Conventionally these junctional sequences are identified using laborious Sanger sequencing of excised heteroduplex bands. We found that the IGH is highly expressed in our diagnostic B-cell acute lymphoblastic leukemia (B-ALL) samples using RNA-Seq. Therefore, we used RNA-Seq to identify IGH disease clone sequences in 258 childhood B-ALL samples for MRD monitoring. The amount of background IGH rearrangements uncovered by RNA-Seq followed the Zipf's law with IGH disease clones easily identified as outliers. Four hundred and ninety-seven IGH disease clones (median 2, range 0-7 clones/patient) are identified in 90.3% of patients. High hyperdiploid patients have the most IGH disease clones (median 3) while DUX4 subtype has the least (median 1) due to the rearrangements involving the IGH locus. In all, 90.8% of IGH disease clones found by Sanger sequencing are also identified by RNA-Seq. In addition, RNA-Seq identified 43% more IGH disease clones. In 69 patients lacking sensitive IGH targets, targeted NGS IGH MRD showed high correlation (R = 0.93; P = 1.3 × 10 -14 ), better relapse prediction than conventional RQ-PCR MRD using non-IGH targets. In conclusion, RNA-Seq can identify patient-specific clonal IGH junctional sequences for MRD monitoring, adding to its usefulness for molecular diagnosis in childhood B-ALL.

A rapid, sensitive and low-fouling sensor for application to detect clinical biomarkers directly in biological media is highly desirable. Herein, we report a versatile strategy to prepare polyaniline (PANI) based conducting polymer hydrogel through the assembly of PANI and phytic acid (PA) by dynamic boronate bond. PANI/PA, a conductive hydrogel with high specific area and multiple pore structures have demonstrated excellent antifouling ability and electrochemical property. The electrochemical biosensors for microRNA can be developed by the immobilization of DNA probes onto PANI/PA interface (microRNA24 is used as a model case), and redox currents of PANI were utilized as the sensing signals to assay DNA/RNA hybridization reaction. Owing to the typical characteristics of PANI/PA hydrogel, the biosensor has shown excellent sensing performances with wide linear range (1.0 fM-1.0 pM), low sensing limit (0.34 fM) and efficient ability to detect microRNA mismatches. Given the facile processability, excellent stability and good antifouling property of the PANI/PA hydrogel, the proposed hydrogel-based biosensor may find broad applications in clinical diagnostics and biomedical devices., 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.)

Objective: To analyze the characteristics of allelic and haplotypic polymorphisms of human leukocyte antigens at HLA-A, -B, -C, DRB1 and DQB1 loci in Guangxi Zhuang population., Methods: Polymerase chain reaction-sequence based typing (PCR-SBT) was used to detect. The five loci (HLA-A, -B, -C, -DRB1, -DQB1) in 350 unrelated Zhuang ethnic individual from Guangxi region. Allelic and haplotypic frequencies were calculated by using Arlequin software 3.5.2.2. Phylogeny tree were constructed by using MEGA software 6.0, and SPSS software was used for principal component analysis., Results: Among the five loci in the population, only HLA-A and DRB1 loci were observed as departures from Hardy-Weinberg expectations. A total of 19 HLA-A, 42 HLA-B, 22 HLA-C, 25 HLA-DRB1 and 15 HLA-DQB1 alleles were found in 350 samples. The most highest frequent alleles were A*11: 01(28.57%), B*46: 01(14.00%), C*01: 02(18.43%), DRB1*16: 02 (15.71%）and DQB1*05: 02 (35.00%) . The most common five loci haplotype was A*33: 03-C*03: 02-B*58: 01-DRB1*03: 01-DQB1*02: 01（6.86%）. The phylogenetic tree analysis showed that Guangxi Zhuang population had a relative close genetic relationship with southern Han Chinese populations., Conclusion: This reaserch found that the HLA-A, B, C, DRB1 and DQB1 loci are highly polymorphic in Guangxi Zhuang population.

A nanocomposite consisting of phytic acid (PA) that was doped with poly(3,4-ethylenedioxy-thiophene) (PEDOT) and modified with copper nanoparticles (CuNPs) was placed on a glassy carbon electrode and then applied in an enzymeless glucose sensor. The undulating PEDOT/PA composite has good conductivity and a large surface area, which was suitable as substrate for the uniform growth of CuNPs. The modified electrode typically operated at a potential near 0.55 V (vs. Ag/AgCl) demonstrated remarkable catalytic activity towards direct oxidation of glucose in NaOH solution (the major limitation of this sensor). Figures of merit include (a) a wide analytical range (5 to 403 μM); (b) high sensitivity (79.27 μA·μM -1 ·cm -2 ), (c) a low detection limit (0.28 μM at a signal to noise ratio of 3), and (d) fast response (< 4 s). Graphical abstractA nanocomposite of phytic acid (PA) doped poly(3,4-ethylenedioxy-thiophene) (PEDOT) modified with copper nanoparticles (CuNPs) onto a glassy carbon electrode was prepared by electrochemical strategy. The CuNPs/PEDOT/PA-modified electrodes were applied in enzymeless glucose sensors with high performance.

To elucidate the mechanism of soybean resistance to Al, physiological and biochemical indices and antioxidant enzyme expression and activities were systematically analyzed in Al-sensitive (Glycine max Merr., Yunnan Province of China, SB) and Al-resistant Dambo (Glycine max Merr., Kyoto of Japan, RB) black soybean plants. According to the results, the contents of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) in RB root tips were significantly lower than those in SB root tips, though the opposite results occurred for soluble protein contents. Moreover, the expression and activities of superoxide dismutase (SOD, EC 1.15.1.1.1.1.1.1 ), peroxidase (POD, EC 1.11.1.7 ) and catalase (CAT, EC 1.11.1.6 ) under 0-400 μM Al for 0-96 h were greater in RB than in SB. However, below 100 μM Al, the activities of those enzymes in SB increased with increasing Al concentration and treatment duration, with SOD activity being lowest and CAT activity exceeding that of POD with increasing Al concentration. Overall, enzyme activity in SB treated with Al at concentrations greater than 200 μM was lower than that in the SB control (CK; not treated with Al) and decreased with treatment duration. Additionally, at Al concentrations lower than 200 μM, enzyme activities in RB were significantly greater than those in RB CK and increased with both Al concentration and treatment duration. Moreover, enzyme activity in RB treated with 400 μM Al was slightly greater than that in RB CK. Thus, CAT activity determines soybean resistance to Al. These results indicate that soybean resistance to Al can be enhanced by regulating the expression and activity of antioxidant enzymes to remove H 2 O 2 under Al stress., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Biocompatible materials, such as zwitterionic poly(carboxybetaine methacrylate) (polyCBMA), are of extraordinary importance in growth of bioelectronics and biosensors, because they not only greatly suppress nonspecific protein adsorption, but also have rich functional groups to facilitate the fixation of biological molecules. A novel nanocomposite was synthesized herein through modification polyCBMA onto conducting polymer polyaniline (PANI) nanowire surface. The prepared polyCBMA/PANI composite, integrating the good conductivity of PANI nanowires with the excellent antifouling capability of polyCBMA, provided a wonderful matrix for the growth of ultrasensitive and low fouling biosensor. Carcinoembryonic antigen (CEA), an important biomarker for a variety of cancers, was utilized as a model test. Furthermore its antibody was fixed onto polyCBMA/PANI for the preparation of CEA biosensor. DPV was applied as a sensing principle with information at which peak potential and current the signals were recorded. The peak currents were in inverse proportion to the logarithm of CEA concentration in the range from 1.0×10 -14 gmL -1 to 1.0×10 -10 gmL -1 , with a detect limit of 3.05fgmL -1 . Furthermore, this low fouling, label-free biosensor has been utilized for assaying in undiluted human serum samples with resisting serious nonspecific protein adsorption, demonstrating its feasible potential application in clinical analysis of CEA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose Although IKZF1 deletion ( IKZF1 del ) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1 del to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1 del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1 del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1 del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1 del was not used in risk assignment, IKZF1 del conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10 -7 ), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1-negative disease, IKZF1 del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1 del significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1 del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1 del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1 del screening significantly improved treatment outcomes in contemporary ALL therapy.

The construction of sensitive and selective biosensors capable of detecting specific targets in complex biological samples remains a challenge highly relevant to a range of sensor/diagnostic applications. Herein, we have utilized a multifunctional peptide to present an interface that supports the very specific recruitment of targets from serum. The novel peptide sequence designed contains an anchoring domain (CPPPP-), an antifouling domain (-NQNQNQNQDHWRGWVA), and a human immunoglobulin G (IgG) recognition domain (-HWRGWVA), and the whole peptide was designed to be antifouling. These were integrated into polyaniline nanowire arrays in supporting the quantification of IgG (with a limit of detection of 0.26 ng mL -1 ) in neat serum and real clinical samples. The strategy of utilizing multisegment peptide films to underpin highly selective target recruitment is, of course, readily extended to a broad range of targets for which an affinity sequence can be generated.

A non-fouling electrochemical immunosensor is described for determination of the tumor biomarker carcinoembryonic antigen (CEA). It is based on the use of composite wires made by chemical grafting of hyaluronic acid onto polyaniline nanowires. The modified nanowires possess excellent antifouling property both in single protein solutions and in dilute serum samples. The current of immunoelectrode exhibits a linear response in the 0.01 pg mL -1 to 10,000 pg mL -1 CEA concentration range and 0.0075 pg mL -1 detection limit. This work demonstrates that coating an electrode with hyaluronic acid can largely reduce unspecific adsorption of proteins on the electrode surface. Graphical abstract Schematic of a nonfouling electrochemical immunosensor for the carcinoembryonic antigen. It is based on novel composite wires made through the chemical grafting of easily available hyaluronic acid (HA) onto polyaniline (PANI) nanowires. The HA/PANI demonstrated excellent antifouling property both in single protein solutions and human serum samples.

Objective GP73 is a new hepatocellular carcinoma (HCC) marker, which is highly expressed in hepatocellular carcinoma and closely relates to prognosis. This study was to investigate the effects of GP73 on cellular proliferation, apoptosis, oxaliplatin (OXA) resistance and secretory clusterin (sCLU) of HCC cells. Materials and Methods Western blot and immunofluorescence was used to detect the expression of GP73 in 8 types of commonly used HCC cell lines. Drug resistance was induced by increasing concentration gradient method. The drug-resistant human HCC cell lines underwent GP73 overexpression or inhibition. Flow cytometry were used to detect the proliferation and apoptosis of HCC cell lines. The changes of sCLU were detected by enzyme-linked immunosorbent assay (ELISA). Results The expression of GP73 in MHC-97H cells was the highest and in Hep3B cells the lowest. The expression of GP73 was found further elevated in OXA-resistant MHC-97H cells. After the knockdown of GP73 in OXA-resistant 97H cells, the IC 50 of OXA decreased and the ability of cell proliferation decreased significantly. After over-expression of GP73 in OXA-resistant Hep3B cells, the IC 50 of OXA increased and the cell proliferation ability increased, showing that GP73 is critical for OXA resistant in HCC cell lines; No significant change of sCLU level in GP73 overexpressed Hep3B and GP73 blocked MHCC-97H were identified. Conclusion The expression level of GP73 is critical for the resistance of OXA in HCC cell lines., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

APE1 is known as a key mediator of DNA damage repair pathways, and its clinical significance in different types of cancer is well studied. Herein, we performed a meta-analysis to determine the association of APE1 expression and survival in different types of solid cancer. We searched all eligible publications in PubMed, Web of Science and Embase platforms from inception to January 2017 and found 15 relevant manuscripts. Overall survival (OS), 12- and 36-month survival rates, and hazard ratios (HRs) were extracted and analyzed. Heterogeneity and publication bias were also assessed. A subgroup analysis of the different subcellular locations of APE1 was also conducted. Patients with higher APE1 levels demonstrated lower 12- and 36-month survival rates than those with low APE1 levels (HR 2.00, 95% CI 1.33-3.00, P = 0.0009; HR 1.84, 95% CI 1.19-2.84, P = 0.006). Importantly, the pooled analysis showed that high levels of APE1 predict shorter OS (HR 1.44, 95% CI 1.13-1.83, P = 0.003). Subgroup analysis revealed that both nuclear and cytoplasmic expression levels of APE1 are important indicators of poor prognosis in solid tumors., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to report.

Aim: To explore the effect of interleukin (IL)-22 on in vitro model of alcoholic liver fibrosis hepatic stellate cells (HSCs), and whether this is related to regulation of Nrf2-keap1-ARE., Methods: HSC-T6 cells were incubated with 25, 50, 100, 200 and 400 μmol/L acetaldehyde. After 24 and 48 h, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect proliferation of HSCs to choose the best concentration and action time. We used the optimal concentration of acetaldehyde (200 μmol/L) to stimulate HSCs for 24 h, and treated the cells with a final concentration of 10, 20 or 50 ng/mL IL-22. The cell proliferation rate was detected by MTT assay. The cell cycle was analyzed by flow cytometry. The expression of nuclear factor-related factor (Nrf)2 and α-smooth muscle antigen was detected by western blotting and immunocytochemistry. The levels of malondialdehyde (MDA) and glutathione (GSH) were measured by spectrophotometry., Results: In the MTT assay, when HSCs were incubated with acetaldehyde, activity and proliferation were higher than in the control group, and were most obvious after 48 h treatment with 200 μmol/L acetaldehyde. The number of cells in G0/G1 phases was decreased and the number in S phase was increased in comparison with the control group. When treated with different concentrations of IL-22, HSC-T6 cell activity and proliferation rate were markedly decreased in a dose-dependent manner, and cell cycle progression was arrested from G1 to S phase. Western blotting and immunocytochemistry demonstrated that expression of Nrf2 total protein was not significantly affected. Expression of Nrf2 nuclear protein was low in the control group, increased slightly in the model group (or acetaldehyde-stimulated group), and increased more obviously in the IL-22 intervention groups. The levels of MDA and GSH in the model group were significantly enhanced in comparison with those in the control group. In cells treated with IL-22, the MDA level was attenuated but the GSH level was further increased. These changes were dose-dependent., Conclusion: IL-22 inhibits acetaldehyde-induced HSC activation and proliferation, which may be related to nuclear translocation of Nrf2 and increased activity of the antioxidant axis Nrf2-keap1-ARE., Competing Interests: Conflict-of-interest statement: The authors declare that no conflict of interest exists in this study.

Inhibition of apoptosis induced by oxidative stress is an effective way to reduce myocardial injury. In this study, we used H2O2-stimulated rat cardiac myoblast cell line (H9c2) as an oxidative damage model. Curcumin (Cur) was chosen as a model drug and mesoporous silica nanoparticles (MSNs) were chosen as the carrier to construct a Cur-loaded delivery system (Cur@MSNs) and to examine its protective effects against oxidative damage. The MSNs guaranteed efficient loading and controlled release of Cur. Besides, the hydrophilicsilanol groups on the surface of MSNs promoted the Cur solubility in water and increased its cellular uptake amount, which improved the bioavailability of Cur. The results suggest that the Cur@MSNs was pharmacologically active in the reduction of the oxidative damage of H9c2 cells. It was verified that a great decrease of reactive oxygen species was inducted by Cur@MSNs, which led to the protective effects against oxidative damage.

Biofouling arising from nonspecific adsorption is a substantial outstanding challenge in diagnostics and disease monitoring, and antifouling sensing interfaces capable of reducing the nonspecific adsorption of proteins from biological complex samples are highly desirable. We present herein the preparation of novel composite nanofibers through the grafting of polyethylene glycol (PEG) polymer onto polyaniline (PANI) nanofibers and their application in the development of antifouling electrochemical biosensors. The PEGylated PANI (PANI/PEG) nanofibers possessed large surface area and remained conductive and at the same time demonstrated excellent antifouling performances in single protein solutions as well as complex human serum samples. Sensitive and low fouling electrochemical biosensors for the breast cancer susceptibility gene (BRCA1) can be easily fabricated through the attachment of DNA probes to the PANI/PEG nanofibers. The biosensor showed a very high sensitivity to target BRCA1 with a linear range from 0.01 pM to 1 nM and was also efficient enough to detect DNA mismatches with satisfactory selectivity. Moreover, the DNA biosensor based on the PEGylated PANI nanofibers supported the quantification of BRCA1 in complex human serum, indicating great potential of this novel biomaterial for application in biosensors and bioelectronics.

An ultrasensitive biosensor for alpha-fetoprotein was developed based on electrochemically synthesized polyaniline (PANI) nanowires, which were functionalized with gold nanoparticles (AuNPs) and polyethylene glycols (PEG). The prepared PEG/AuNPs/PANI composite, combining the electrical conductivity of the AuNPs/PANI with the robust antifouling ability of PEG, offered an ideal substrate for the development of low fouling electrochemical biosensors. Alpha-fetoprotein (AFP), a well-known hepatocellular carcinoma biomarker, was used as a model analyte, and its antibody was immobilized on the PEG/AuNPs/PANI for the construction of the AFP immunosensor. Using the redox current of PANI as the sensing signal, in addition to the good biocompatibility of PEG/AuNPs and the anti-biofouling property of PEG, the developed immunosensor showed improved biosensing performances, such as wide linear range and ultralow detection limit (0.007pgmL(-1)). More importantly, it is label-free, reagentless and low fouling, making it capable of assaying AFP in real serum samples without suffering from significant interference or biofouling., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To identify a novel human leukocyte antigen (HLA) allele HLA-B*13:92 and analyze 3D model of HLA molecule., Methods: Polymerase chain reaction sequencing-based (PCR-SBT) was used in routine HLA typing, the B locus typing results of one sample was one base mismatch with B*13:01:01, B*58:01:01 at locus 189, The Group Specific Sequencing Products (GSSP) which target at B*13 and B*58 were used to confirm difference between the new allele and highest homologous allele, then the new allele was modeled by Swiss-model to its 3D structure., Results: The sequencing results showed that the new allele with highest homologous allele B*13:01:01 was the difference in the second exon at position 189 C>A (codon 39 GAC>GAA), 39 Asp (D) was changed to Glu (E). The amino acid substitution at residue 39 of the HLA polypeptide was located in α-helices of antigenic peptide-biding region., Conclusion: This allele is a new HLA-B allele found in Chinese Guangxi Zhang population and has been designated as HLA-B*13:92 by the World Health Organization (WHO) HLA Nomenclature Committee.

A highly stable and sensitive nonenzymatic glucose sensor was successfully constructed through a facile electrodeposition method. Graphene oxide (GO) doped poly(3,4-ethylenedioxythiophene) (PEDOT) was first electrodeposited onto a glass carbon electrode using cyclic voltammetry and copper nanoparticles were then electrodeposited onto the rough surface of the PEDOT/GO nanocomposite through electrochemical reduction in a solution containing copper cations. The modified electrode was used for reliable nonenzymatic electrochemical detection of glucose, and under optimized conditions, it exhibited a high sensitivity of up to 909.1 μA mM -1 cm -2 and a very fast response time of less than 1 s, with a wide linear range of 0.1 μM to 1.3 mM and a low detection limit of 47 nM. This nonenzymatic glucose sensor was, furthermore, highly stable and unresponsive to potentially interfering substances, and it could be used for the assay of glucose in real human serum samples. These enhanced sensing performances were ascribed to the close contact of copper nanoparticles onto the rough surface of the PEDOT/GO conducting polymer nanocomposite, which has good conductivity and very high surface area that can act as an excellent substrate for the growth and support of copper nanoparticles. All these results indicate that this electrochemical sensor is highly promising for nonenzymatic glucose detection.

Background: Zinc-binding protein-89 (ZBP-89), a Krüppel-type four-zinc finger transcription factor, is associated with many cellular functions, including cell growth, differentiation, and apoptosis. It has been reported to be involved in several human cancers. However, ZBP-89 expression pattern and its clinical significance have not yet been investigated in esophageal squamous cell cancer., Methods: In this study, immunostaining was performed to detect ZBP-89 expression in esophageal squamous cell cancer, and then the correlations between ZBP-89 expression and both clinicopathologic variables and overall survival were analyzed., Results: Compared with adjacent normal tissues, ZBP-89 expression was significantly upregulated in esophageal squamous cell cancer tissues. Increased ZBP-89 expression was associated with N category (p = 0.009) and TNM stage (p = 0.023). Patients with high expression of ZBP-89 demonstrated shortened overall survival compared with those with low expression of ZBP-89 (mean overall survival, 56.961 months versus 76.029 months; p < 0.001). Multivariate Cox regression analysis indicated that ZBP-89 expression had a significant, independent predictive value for survival of esophageal squamous cell cancer (relative risk, 1.581; p = 0.024)., Conclusions: Our data show that increased expression of ZBP-89 is associated with poor prognosis for esophageal squamous cell cancer patients and may act as a novel, useful, and independent prognostic indicator for esophageal squamous cell cancer. Further studies are warranted., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Pien Tze Huang (PZH) is a well-known Chinese medicine that has been used as a therapeutic drug in the treatment of a number of diseases, such as hepatocellular carcinoma and colon cancer. However, few studies have analyzed the effects of PZH on ovarian cancer cell proliferation. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays, cell cycle and apoptosis rate analyses and western blotting were conducted to investigate the effects of PZH on the proliferation rate of ovarian cancer cells and its potential molecular pathway. The results showed that PZH inhibits the proliferation of the human ovarian cancer OVCAR-3 cell line by blocking the progression of the cell cycle from the G 1 to S phase, however, PZH did not induce OVCAR-3 cell apoptosis. Increased PZH concentration may downregulate the expression of AKT, phosphorylated (p)-AKT, mammalian target of rapamycin (mTOR) and p-mTOR proteins in the OVCAR-3 cell line. In addition, it was observed that PZH may suppress the protein expression of cyclin-dependent kinase (CDK)4 and CDK6. Overall, the results of the present study indicated that PZH may inhibit ovarian cancer cell proliferation by modulating the activity of the AKT-mTOR pathway.

Many studies have examined the association between the MGMT Leu84Phe polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to Nov. 2013. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 7 studies, comprising 3,094 lung cancer cases and 4,216 controls, were included. Overall, for (Phe/Phe+Phe/Leu) versus Leu/Leu, the pooled OR for all studies was 1.08 (95% CI = 0.97-1.21 P = 0.518 for heterogeneity); for Phe/Phe versus Leu/Leu and Phe versus Leu, the pooled OR was 1.10 (95% CI = 0.99-1.21 P = 0.445 for heterogeneity) and 1.46 (95% CI = 1.05-2.02 P = 0.352 for heterogeneity), respectively. In the stratified analysis by ethnicity, significantly risks were found among Caucasians not in Asians. This meta-analysis suggests that the MGMT Leu84Phe polymorphisms are associated with lung cancer risk among Caucasians not in Asians.

Unlabelled: The aim of this study was to evaluate the association of polymorphic genotypes in the cyclooxygenase 2 gene (COX2), which is reported to be overexpressed in prostate tumors, with Taiwan prostate cancer patients., Materials and Methods: Six polymorphic variants of COX2 were analyzed for their association with prostate cancer susceptibility. A total of 218 patients with prostate cancer and 436 healthy controls in central Taiwan were enrolled in this investigation. P-values and odds ratios with 95% confidence intervals were used to assess the strength of the association., Results: Among the six polymorphic sites examined, only the Cox-2 promoter G-765C (rs14133) genotypes were distributed differently between the prostate cancer and control groups. The COX2 -765GG genotype was associated with higher prostate cancer risk than -765GC., Conclusion: These findings provide evidence that the G allele of COX2 promoter G-765C may be associated with the development of prostate cancer and may be a useful marker for early detection of prostate cancer.

Aim: Several epidemiological studies have investigated the association between ataxia telangiectasia mutated (ATM) gene polymorphisms and breast cancer risk. However, published data are still inconclusive and there are no such studies for Taiwan. Thus, the polymorphic variants of ATM were investigated for their association with breast cancer in Taiwan for the first time here., Patients and Methods: In this hospital-based matched case-control study, associations of seven ATM single nucleotide polymorphisms (rs600931, rs652311, rs227060, rs227292, rs624366 and rs189037) with breast cancer risk in a Taiwanese population were investigated. One thousand two hundred and thirty-two patients with breast cancer and the same number of age-matched healthy controls recruited were genotyped and analyzed., Results: There was a slight difference between breast cancer and control groups in the distributions of their genotypic (p = 0.0774) and allelic frequencies (p = 0.0217) in the rs189037 polymorphism. As for the other six polymorphisms there was no differential distribution., Conclusion: Our data indicate that ATM polymorphism is associated with breast cancer, and the A allele of ATM rs189037 is a minor risky biomarker of breast cancer in Taiwan. The gene-gene and gene-environment interactions of ATM with other factors is worthy of further investigation.

Nur77 is a steroid orphan receptor that plays a critical role in regulating proliferation, differentiation, and apoptosis, including acting as a switch for Bcl-2 function. We previously reported that the octaketide cytosporone B (Csn-B) is a natural agonist for Nur77. In this study, we synthesized a series of Csn-B analogues and performed a structure-activity analysis that suggested criteria for the development of a unique pharmacophore to activate Nur77. The components of the pharmacophore necessary for binding Nur77 included the benzene ring, the phenolic hydroxyl group, and the acyl chain of the Csn-B scaffold, whereas the key feature for activating the biological function of Nur77 was the ester group. Csn-B analogues that bound Nur77 tightly not only stimulated its transactivation activity but also initiated mitochondrial apoptosis by means of novel cross-talk between Nur77 and BRE, an antiapoptotic protein regulated at the transcriptional level. Notably, the derivative n-amyl 2-[3,5-dihydroxy-2-(1-nonanoyl)phenyl]acetate exhibited greater antitumor activity in vivo than its parent compounds, highlighting particular interest in this compound. Our findings describe a pathway for rational design of Csn-B-derived Nur77 agonists as a new class of potent and effective antitumor agents., ((c)2010 AACR.)

The electrochemical behaviors of the interaction of chromotrope 2R (CH2R) with human serum albumin (HSA) are investigated on the hanging mercury drop electrode with linear sweep voltammetry. In the acidic buffer solution (pH 2.5) CH2R has a well-defined voltammetric reductive wave at -0.34 V (SCE). On the addition of HSA into the CH2R solution, the reductive peak current of CH2R decreases with little movement of the peak potential. The voltammetric study shows that the electrochemical parameters of interaction solution do not change and a new electrochemically non-active complex is formed via interaction of CH2R with HSA, which cannot be reduced on the Hg electrode and results in the decrease of the free concentration of CH2R. The decrease of reductive peak current is proportional to HSA concentration and further used for protein detection. The binding ratio and the binding constant are further calculated with the experimental voltammetric data.

Objective: To design new models that combine clinical variables and biopsy data with magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) data, and assess their value in predicting the probability of insignificant prostate cancer., Patients and Methods: In all, 220 patients (cT stage T1c or T2a, prostate-specific antigen level <20 ng/mL, biopsy Gleason score 6) had MRI/MRSI before surgery and met the inclusion criteria for the study. The probability of insignificant cancer was recorded retrospectively and separately for MRI and combined MRI/MRSI on a 0-3 scale (0, definitely insignificant; - 3, definitely significant). Insignificant cancer was defined from surgical pathology as organ-confined cancer of

Purpose: To retrospectively determine whether endorectal magnetic resonance (MR) imaging findings contribute incremental value to the Kattan nomogram for predicting seminal vesicle invasion (SVI) in patients with prostate cancer., Materials and Methods: The institutional review board issued a waiver of authorization, which included a waiver of informed consent, for this HIPAA-compliant study. From October 2000 through January 2005, 573 patients (mean age, 58.3 years; age range, 36-86 years) underwent endorectal MR imaging before prostate cancer surgery. The endorectal MR imaging results had been prospectively interpreted by seven radiologists, and the likelihood of SVI was retrospectively scored on the basis of radiologists' written reports. MR imaging findings, individual clinical variables (serum prostate-specific antigen [PSA] level, Gleason grade, clinical stage, greatest percentage of cancer in all biopsy cores, percentage of positive cores in all biopsy cores, and perineural invasion), and the Kattan nomogram were evaluated with respect to SVI prediction; surgical pathologic analysis was used as the reference standard. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed., Results: At pathologic analysis, 28 (4.9%) of 573 patients had SVI. At univariate analysis, endorectal MR imaging results and all clinical variables except the percentage of positive biopsy cores were significantly associated with SVI (P<.02); endorectal MR imaging (0.76) had a larger area under the ROC curve (AUC) than any clinical variable (0.62-0.73). At multivariate analysis, endorectal MR imaging results, Gleason grade, PSA level, and the percentage of cancer in all biopsy cores were significantly associated with SVI (P