Background-Free SERS Nanosensor for Endogenous Hydrogen Sulfide Detection Based on Prussian Blue-Coated Gold Nanobipyramids.

Surface-enhanced Raman scattering (SERS) has great potential in biological analysis due to its specificity, sensitivity, and non-invasive nature. However, effectively extracting Raman information and avoiding spectral overlapping from biological background interference remain major challenges. In this study, we developed a background-free SERS nanosensor consisting of gold nanobipyramids (Au NBPs) core-Prussian blue (PB) shell (Au NBPs@PB), for endogenous H2S detection. The PB shell degraded quickly upon contact with endogenous H2S, generating a unique Raman signal response in the Raman silent region (1800-2800 cm-1). By taking advantage of the high SERS-activity of Au NBPs and H2S-triggered spectral changes of PB, these SERS nanosensors effectively minimize potential biological interferences. The nanosensor exhibits a detection range of 2.0 µM to 250 µM and a limit of detection (LOD) of 0.34 µM, with good reproducibility and minimal interference. We successfully applied this background-free SERS platform to monitor endogenous H2S concentrations in human serum samples with satisfied results.

Highly specific and sensitive sandwich-type electrochemiluminescence biosensor for HPV16 DNA detection based on the base-stacking effect and bovine serum albumin carrier platform.

The detection of specific DNA sequences and the identification of single nucleotide polymorphisms are important for disease diagnosis. Herein, by combining the high specificity of the base-stacking effect with the high reproducibility of bovine serum albumin (BSA) modified electrodes and the high loading performance of DNA nanoclews (DNA NCs), a novel sandwich-type electrochemiluminescence (ECL) biosensor is reported for the highly specific detection of HPV16 (chosen as the model target). The capture probes are loaded by BSA carrier platforms modified on the gold electrode surface to improve reproducibility. DNA NCs loaded with a large amount of Ru(phen)32+ worked as signal probes. The template probe is composed of the complementary strand of the target and two free nucleic acid anchors at the head and tail. In the presence of the target DNA, the template probes can form stacked base pairs with target, generating high base-stacking energy. This results in the shorter free anchors of template probes being able to bind to the capture and signal probes. This eventually forms a sandwich structure that allows Ru(phen)32+ to be near the electrode surface, producing an ECL signal. There is a linear relationship between the signal and the target concentration range from 10 fM to 100 pM, with a detection limit of 5.03 fM (S/N=3). Moreover, the base-stacking effect has single base recognition ability for base pairs, effectively avoiding false positive signals. The results of this strategy for clinical samples are consistent with classical methods.

Evaluation of a two-test strategy for HIV screening in a low-prevalence setting and the indications for optimizing clinical management.

Objectives: To evaluate a two-test strategy for HIV screening in the low-prevalence population and to assess the feasibility of utilizing the optimal signal-to-cutoff (S/CO) threshold on the chemiluminescence immunoassay(CMIA) and an additional rapid test on the gold immune-chromatography assay (GICA) for screening positive patients and optimization of clinical management. Methods: We conducted a retrospective study of samples analyzed by the fourth-generation Architect HIV Ag/Ab combo assay (CMIA) in a large medical center between June 2017 and August 2020. Reactive samples underwent a second screening test using the rapid test GICA, followed by Western blot (WB) as the confirmatory test. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal S/CO. We calculated sensitivity, specificity, and predictive value based on our population. The performance of the single-test strategy (CMIA) was compared with that of the two-test strategy (CMIA and GICA). Logistic regression was used to analyze the factors of clinical characteristics leading to false positive results. Results: A total of 220558 samples were screened by CMIA, and 429 patients met the inclusion criteria. Of these, CMIA produced 199 false-positive results with a median S/CO of 1.93(IQR1.45-3.68) and 230 positive results with a median S/CO of 455.1 (IQR169.3-709.7). The optimal S/CO of the single-test strategy was 8.82, which achieved a sensitivity of 100% and a positive predictive value (PPV) of 90.9%. The two-test strategy (CMIA and GICA) provided a sensitivity of 100% and a PPV of 98.7%, which best correlated with the confirmatory test WB. The combination of S/CO 8.82 on the CMIA assay and additional test results of GICA can be defined as four types used to interpret HIV serostatus. The false positive rate (FPR) was high in the female, the age≤18 group, the pre-operative patients, and the patients from the clinical departments of Pediatrics, Gynecology and Obstetrics, and Oncology, etc. Conclusions: The false positive rate is high in the low-prevalence setting by using CMIA. The two-test strategy (CMIA and GICA) is recommended for HIV screening in hospitals. Hopefully, the clinicians will be able to interpret HIV serostatus and facilitate clinical decision-making while waiting for the confirmatory results.

A Cross-Sectional Study of Clostridium Difficile Infection in Inpatients with Antibiotic Associated Diarrhea.

BACKGROUND: Clostridium difficile (C. difficile) is a Gram-positive, anaerobic, spore-forming bacillus that can cause pseudomembranous colitis and other C. difficile-associated diseases, resulting in significant morbidity and mortality. The incidence and clinical features vary by geography. METHODS: In this cross-sectional study, we examined the incidence and clinical features of C. difficile infection (CDI) within a 2,900-bed academic medical center in a southern area of China from January 1, 2017, to December 31, 2020. All adult inpatients (aged ≥ 18 years) who submitted loose stool samples for C. difficile testing over this period were considered for the study. RESULTS: This cross-sectional study showed that the average incidence of CDI was 2.07 cases/100,000 hospital patient-days. The mean age of these inpatients was 71.21 ± 2.83 years (range 30 - 93 years), and 83.61% (51/61) were treated in medical units. We found that 85.25% (52/61) of inpatients with CDI were aged > 60 years. Multivariate logistic regression analysis revealed that age > 60 years, and admission to the geriatric treatment unit or neurosurgery treatment unit were indeed independent risk factors for CDI in inpatients. CONCLUSIONS: The incidence of CDI in the southern area of China was low. Age > 60 years, and treatment in geriatric or neurosurgery units were independent risk factors for CDI inpatients.

The association of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage in patients with chronic hepatitis B.

The utility of measurement of serum immunoglobulin and complement in chronic hepatitis B (CHB) patients remains controversial. This study aimed to investigate the association of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage in CHB patients. A total of 687 patients with CHB who underwent liver biopsy were enrolled. Serum immunoglobulin and complement were measured before liver biopsy, and liver pathological results were recorded. Associations of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage were analysed. C3, C4, IgG and IgG1 had statistically significant differences among different fibrosis and different inflammation groups. Both C3 and C4 negatively correlated with fibrosis and inflammation stage, but IgG and IgG1 showed opposite results. C3, C4, IgG and IgG1 had statistical significance to predict ≥S2, ≥S3 and S4, and also had statistical significance to predict ≥G2, ≥G3 and G4. The area under curve (AUC) of the combination of C3, C4 and IgG (C3 + C4 + IgG) for predicting ≥S2, ≥S3 and S4 was 0.640 (95% CI: 0.603, 0.676), 0.674 (95% CI: 0.638, 0.709) and 0.744 (95% CI: 0.710, 0.776), respectively. The AUC of C3 + C4 + IgG for predicting ≥G2, ≥G3 and G4 was 0.723 (95% CI: 0.688, 0.756), 0.674 (95% CI: 0.638, 0.709) and 0.771 (95% CI: 0.738, 0.802), respectively. C3, C4, IgG and IgG1 are correlated with liver fibrosis and inflammation stage in CHB patients. C3, C4, IgG and IgG1 have diagnostic value for liver fibrosis and inflammation. C3 + C4 + IgG may improve diagnostic accuracy.

Evaluating the value of anti-SARS-CoV-2 antibody detection and neutralizing responses with euvirus: A population of 10776 close contacts in the epidemic of Fujian.

BACKGROUND: Nucleic acid detection represents limitations due to its false-negative rate and technical complexity in the COVID-19 pandemic. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests are widely spread all over the world presently. However, there is no report on the effectiveness of anti-SARS-CoV-2 antibody testing methods in China. METHODS: We gathered 10776 serum samples from close contacts of the SARS-CoV-2 infections in Fujian of China and used 2 chemiluminescence immunoassays (Wantai Bio., Yahuilong Bio.) and 2 lateral flow immunoassays (Lizhu Bio. and Dongfang Bio.) to perform the anti-SARS-CoV-2 antibody tests in China. RESULTS: The 4 antibody tests have great diagnostic value for infected or uninfected, especially in the neutralizing antibodies tests, the AUC can reach 0.939 (Wantai Bio.) and 0.916 (Yahuilong Bio.). Furthermore, we used pseudoviruses and euvirus neutralization assay to validate the effectiveness of these antibody test, the results of pseudoviruses neutralization assay or euvirus neutralization assay shows a considerable correlation with the 4 antibody detection respectively, particularly in euvirus neutralization assay, neutralizing antibodies detected by Wantai Bio. or Yahuilong Bio., the correlation can get the level of 0.93 or 0.82. CONCLUSIONS: The findings of this study demonstrate that the detections of antibodies have profound value in the diagnosis of COVID-19.

Effectiveness of SARS-CoV-2-inactivated vaccine and the correlation to neutralizing antibodies: A test-negative case-control study.

Severe acute respiratory syndrome coronavirus 2 breakthrough infection in highly vaccinated populations raises study on the effectiveness for inactivated vaccine, including effectiveness of the vaccine dose, the continuance of effectiveness, the effectiveness against severe/critical coronavirus disease 2019 and against secondary attacks. A population of 10 870 close contacts were investigated in a Delta variant's epidemic. The effectiveness of vaccination was estimated in a test-negative case-control study. In addition, serum was used to detect neutralizing antibodies, to explore their correlation to effectiveness. The vaccine effectiveness (VE) values were estimated for populations aged 12 years or older. The overall adjusted VE was 56.2% and a two-dose vaccine was more effective than a one-dose vaccine (56.7% vs. 43.8%). In addition, the population that got the second dose vaccine within 2 months showed higher VE than the population vaccinated for longer than 2 months (61.5% vs. 52.3%). Among the population who vaccinated 2 doses or within 2 months, a higher level of neutralizing antibodies was observed. For infected cases, vaccinated populations showed lower rates of transmission (2.63% vs. 4.36%). Further, those vaccinated cases, who were not found causing transmission, had a higher level of antibodies. The study provided a full view of the effectiveness of inactivated vaccines in a real-world setting. The time-related VE against infection and lower transmission of breakthrough vaccinated cases were observed, which may indicate that a necessity of a booster vaccine to maintain the effectiveness and high level of neutralizing antibody.

Assessing the risk of prenatal depressive symptoms in Chinese women: an integrated evaluation of serum metabolome, multivitamin supplement intake, and clinical blood indicators.

Background: Prenatal depressive symptoms (PDS) is a serious public health problem. This study aimed to develop an integrated panel and nomogram to assess at-risk populations by examining the association of PDS with the serum metabolome, multivitamin supplement intake, and clinical blood indicators. Methods: This study comprised 221 pregnant women, categorized into PDS and non-PDS groups based on the Edinburgh postnatal depression scale. The participants were divided into training and test sets according to their enrollment time. We conducted logistic regression analysis to identify risk factors, and employed liquid chromatography/high resolution mass spectrometry-based serum metabolome analysis to identify metabolic biomarkers. Multiple factor analysis was used to combine risk factors, clinical blood indicators and key metabolites, and then a nomogram was developed to estimate the probability of PDS. Results: We identified 36 important differential serum metabolites as PDS biomarkers, mainly involved in amino acid metabolism and lipid metabolism. Multivitamin intake works as a protective factor for PDS. The nomogram model, including multivitamin intake, HDL-C and three key metabolites (histidine, estrone and valylasparagine), exhibited an AUC of 0.855 in the training set and 0.774 in the test set, and the calibration curves showed good agreement, indicating that the model had good stability. Conclusion: Our approach integrates multiple models to identify metabolic biomarkers for PDS, ensuring their robustness. Furthermore, the inclusion of dietary factors and clinical blood indicators allows for a comprehensive characterization of each participant. The analysis culminated in an intuitive nomogram based on multimodal data, displaying potential performance in initial PDS risk assessment.

METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumourigenesis.

METTL3 encodes the predominant catalytic enzyme to promote m6A methylation in nucleus. Recently, accumulating evidence has shown the expression of METTL3 in cytoplasm, but its function is not fully understood. Here we demonstrated an m6A-independent mechanism for METTL3 to promote tumour progression. In gastric cancer, METTL3 could not only facilitate cancer progression via m6A modification, but also bind to numerous non-m6A-modified mRNAs, suggesting an unexpected role of METTL3. Mechanistically, cytoplasm-anchored METTL3 interacted with PABPC1 to stabilize its association with cap-binding complex eIF4F, which preferentially promoted the translation of epigenetic factors without m6A modification. Clinical investigation showed that cytoplasmic distributed METTL3 was highly correlated with gastric cancer progression, and this finding could be expanded to prostate cancer. Therefore, the cytoplasmic METTL3 enhances the translation of epigenetic mRNAs, thus serving as an oncogenic driver in cancer progression, and METTL3 subcellular distribution can assist diagnosis and predict prognosis for patients with cancer.

Co-Reactant-Mediated Low-Potential Anodic Electrochemiluminescence Platform and Its Immunosensing Application.

Screening high-performance anodic electrochemiluminescence (ECL) systems with low triggering potential is a promising way to broaden their applications. In addition to electrochemiluminophore, co-reactant also plays an important role in the ECL process, since the oxidation of co-reactants is one of the most important steps in the anodic ECL process. Herein, a novel co-reactant-mediated high-performance low-potential Au nanocluster (AuNC)-based ECL system has been successfully developed. Benefiting from the isopropyl substitution and hydroxyl addition to the triethylamine (TEA), the BSA-AuNC/2-(diisopropylamino)ethanol (DIPEA-OH) ECL system achieved higher energy efficiency at a lower potential of 0.75 V. In addition, compared with the BSA-AuNC/TEA system, the ECL intensity and quantum yield (ΦECL) with DIPEA-OH as a co-reactant increased 22.34-fold and 13-fold (as high as 68.17%), respectively. Based on the low potential, high ΦECL of the AuNC/DIPEA-OH ECL system, a sandwich-type immunosensor has been constructed for a highly selective SARS-CoV-2 N protein assay. In the absence of any complex signal amplification strategies, the ECL immunosensor for the SARS-CoV-2 N protein detection showed a linear range of 0.001-100 ng/mL and a detection limit of 0.35 pg/mL. Moreover, the ECL platform had good reproducibility and stability and exhibited acceptable detection performance in the detection of actual serum samples. This work established a framework for in-depth design and study of anode ECL co-reactants for AuNCs and other luminophores, and expanded the potential application of ECL sensors in the clinical diagnosis of COVID-19.

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

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

Highly reproducible and sensitive electrochemical biosensor for Chlamydia trachomatis detection based on duplex-specific nuclease-assisted target-responsive DNA hydrogels and bovine serum albumin carrier platform.

16S ribosomal-RNA (16S rRNA) is often used as an ultrasensitive marker for Chlamydia trachomatis (CT) detection because of its species specificity and high copy number in CT. Robust methods for 16S rRNA detection must be developed to realize the early diagnosis of CT infections. In this work, a highly reproducible and sensitive electrochemical biosensor based on duplex-specific nuclease (DSN)-assisted target-responsive DNA hydrogels and bovine serum albumin (BSA) carrier platform for CT detection was developed. Target rRNA can trigger the DNA hydrogel response, which causes it to be repeatedly cleaved by DSN, ultimately leading to the release of a large amount of horseradish peroxidase-labelled streptavidin (SA-HRP) embedded in the hydrogel beforehand. The released SA-HRP was stably captured by the capture probes that were orderly loaded at the gold electrode with the help of a BSA layer. Then, SA-HRP catalyzed the redox reaction of 3,3',5,5'-tetramethylbenzidine and H2O2, producing a current signal that can be detected. The current signal was proportional to the concentration of CT 16S rRNA from 10 fM to 25 pM with a detection limit of 5.8 fM (S/N = 3). The signal conversion function of the DNA hydrogel avoids the instability of nonhomogeneous nucleic acid hybridization on the gold electrode surface, and combined with optimization by BSA for capture probe modification, this electrochemical biosensor is highly reproducible with a relative standard deviation of 4.3% for the detection of 10 samples of the same concentration. The proposed strategy provides a highly reproducible and sensitive detection method for the extensive screening of CT.

Association Between Diet-Related Inflammation and COPD: Findings From NHANES III.

Background and Aims: Little is known about diet-related inflammation in chronic obstructive pulmonary disease (COPD). In this study, we aimed to explore the association between COPD and dietary inflammatory index (DII) scores in adults over 40 years old. Methods: Data were obtained from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES). In the present study, 9,929 participants were included and analyzed. The DII score was calculated and divided into tertiles. Logistic regression analysis was performed to determine the odds ratios of DII tertiles. Results: Participants were categorized into COPD (565, 5.69%) and non-COPD groups (9,364, 94.31%) according to interview information. COPD individuals had higher DII scores than non-COPD individuals (0.429 ± 1.809 vs. -0.191 ± 1.791, p < 0.001). The highest DII score tertile included 46.55% of COPD individuals was associated with lower family incomes and education and a higher smoking rate (p < 0.01). The odds ratios (95% CIs) of COPD according to logistic regression were 0.709 (0.512-0.982) for T1 and 0.645 (0.475-0.877) for T2 of the DII score (p = 0.011). Conclusion: Higher DII scores were positively correlated with COPD in participants over 40 years old. These results further support that diet can be used as an intervention strategy for COPD management.

Electrochemiluminescence Immunoassay Platform with Immunoglobulin G-Encapsulated Gold Nanoclusters as a "Two-In-One" Probe.

Biomolecule-functionalized Au nanoclusters (AuNCs) have drawn great interest in the electrochemiluminescence (ECL) field due to their unique optical/electrical properties, biocompatibility, and versatile bioapplication potentials. Herein, we proposed a two-in-one ECL probe of immunoglobulin G-encapsulated AuNCs (IgG-AuNCs) for the development of a high-performance ECL immunoassay (ECLIA) platform. The IgG-AuNCs were not only used as an ECL probe due to their excellent anodic ECL performance with triethylamine (TEA) as a coreactant but also used as the biorecognition element because of their well-retained bioactivity of the IgG. As a proof of concept, a new type of competitive immunosensing platform has been applied to detect IgG representing several merits of facile preparation, rapid detection, sample saving, and good analytical performance. The sensing platform exhibited a linear range of 0.5-50,000 ng/mL with a limit of detection of 0.06 ng/mL for IgG detection with high selectivity. In addition, this convenient ECLIA platform also performed well in real serum sample detection. Notably, our work not only proved the "two-in-one" immuno-AuNC probe-based ECLIA strategy but also developed a rational framework for study of ECL bioassay platforms based on multifunctional AuNCs and other related nanomaterials.

High-throughput chromosome conformation capture-based analysis of higher-order chromatin structure in nasopharyngeal carcinoma.

BACKGROUND: Firstly, we aimed to compare the differences of higher-order chromatin structure between nasopharyngeal carcinoma (NPC) and normal nasopharyngeal tissues. The second objective was to analyze the specific chromatin interaction site of NPC and the NPC-related genes regulated by this interaction site. METHODS: We included 6 NPC patients and 6 healthy controls to obtain the sequencing results of highest-throughput chromosome conformation capture (Hi-C) technique, followed by further analysis of the specific chromatin interaction sites in NPC. RESULTS: We found an abnormal ultra-long distance interaction site on the chromosome 7p in the CNE210 sample, which was caused by a fusion gene SEPT7P2-PSPH. Additionally, a significant interaction site between chromosome 8q and 3p was revealed in the samples CNE25, CNE29, and CNE211, which was the interaction between 1.5 kb downstream of ASAP1 and 0.8 kb upstream of CTNNB1 gene. Further quantitative polymerase chain reaction (qPCR) revealed that ASAP1 and CTNNB1 genes were more highly expressed in CNE25, CNE29, and CNE211 than in the Np group, preliminarily indicating that this interaction site was likely related to the high expression of ASAP1 and CTNNB1 in NPC. CONCLUSIONS: Through Hi-C analysis, we analyzed the specific chromatin interaction sites associated with NPC, and found the chromosomal translocation and chromatin interaction sites associated with NPC based on statistical analysis. This study has certain guiding significance for in-depth study of the mechanism of NPC occurrence and development.

G-protein-coupled receptor GPR17 inhibits glioma development by increasing polycomb repressive complex 1-mediated ROS production.

Glioma is the most common primary tumor in the central nervous system. However, the development of glioma and effective therapeutic strategies remain elusive. Here, we identify GPR17 as a potential target to treat glioma. Data mining with human LGG and GBM samples reveals that GPR17 is negatively correlated with glioma development. Overexpressing GPR17 inhibits glioma cell proliferation and induces apoptosis by raising ROS levels. GPR17-overexpressing glioma cells are less tumorigenic in the brain than in control cells. Mechanistically, GPR17 inhibits the transcription of RNF2, a key component in the PRC1 complex, through cAMP/PKA/NF-κB signaling, leading to reduced histone H2A monoubiquitination. ChIP-Seq and RNA-Seq analyses reveal KLF9 as a direct target of RNF2. KLF9 mediates the functions of GPR17 and RNF2 in glioma cells. Furthermore, activation of GPR17 by its agonist inhibits glioma formation. Our findings have thus identified GPR17 as a key regulator of glioma development and a potential therapeutic target for gliomas.

Diagnostic Value of Vaginal Microecology, Serum miR-18a, and PD-L1 for Identifying HPV-Positive Cervical Cancer.

OBJECTIVE: We aimed to investigate the diagnostic value of the vaginal microecology, serum miR-18a, and programmed death ligand-1 (PD-L1) for human papillomavirus (HPV)-positive cervical cancer. METHODS: Eighty-four patients with HPV-positive cervical cancer were assigned to the observation group, 107 HPV-positive patients without cervical cancer were assigned to the positive group, and 191 healthy women were assigned to the control group. Vaginal microecology and serum levels of miR-18a and PD-L1 on the surface of CD4+ and CD8+ T cells were compared among the 3 groups. The observation group was further divided into subgroups according to patients' characteristics for comparison. The diagnostic value of miR-18a and PD-L1 for HPV-positive cervical cancer was investigated. RESULTS: Women in the control group had better vaginal microecology and lower levels of miR-18a and PD-L1 than those in the observation and the positive groups (all P < 0.05). Compared with the positive group, the observation group had similar vaginal microecology (all P > 0.05) but higher levels of miR-18a and PD-L1 (all P < 0.05). Moreover, the patients at stage III had higher levels of miR-18a and PD-L1 than those at stage I and II (all P < 0.05). The values of area under the curve for miR-18a and PD-L1 in the diagnosis of HPV-positive cervical cancer were over 0.8 (all P < 0.001). CONCLUSION: Patients with HPV-positive cervical cancer have vaginal microbial dysbiosis and high serum levels of miR-18a and PD-L1. miR-18a and PD-L1 have diagnostic value for identifying HPV-positive cervical cancer.

Split-type electrochemiluminescent gene assay platform based on gold nanocluster probe for human papillomavirus diagnosis.

Persistent high-risk human papillomavirus (HPV) infection is the leading cause of cervical cancer. Efficient detection of HPV16 E7 is necessary for early diagnosis and cure of the disease. Here, a novel and high-performance Au nanocluster (AuNC) probe-based split-type electrochemiluminescent (ECL) assay platform has been established to detect these oncogenes, in which the nucleic acid hybridization assay and the ECL measurements are performed independently. The proposed approach combines superior magnetic nanobead enrichment and separation technology, specific nucleic acid hybridization technology, and high-efficiency AuNC probe ECL strategy, and shows excellent advantages. First, the split-type ECL sensing platform can effectively avoid interference from biological samples and adequately uses the ECL efficiency of the AuNC probe. Furthermore, the ultrahigh sensitivity assay of HPV DNA can be achieved without any complex nucleic acid amplification technique. Taking advantage of the above merits of split-type detection, the ECL DNA sensor achieved ideal low detection of 6.8 aM and a wide dynamic range bridging 10 orders of magnitude HPV16 E7. Furthermore, together with its favorable and powerful specificity, high sensitivity, and good selectivity, this strategy could detect HPV16 E7 DNA in human samples, which showed great consistency with the FDA-approved approach (Hybrid capture 2, HC2). Therefore, this work proposes a facile and reliable split-type ECL platform for HPV diagnosis and shows great potential for the early diagnosis of other diseases.

Highly Reproducible and Sensitive Electrochemiluminescence Biosensors for HPV Detection Based on Bovine Serum Albumin Carrier Platforms and Hyperbranched Rolling Circle Amplification.

Most DNA-based electrochemiluminescence (ECL) biosensors are established through the self-assembly of thiolated single-stranded DNA (ssDNA) probes on the Au electrode surface. Because of this random assembly process, a significant discrepancy exists in the distribution of a modified DNA film on different electrodes, which greatly affects the reproducibility of a biosensor. In this study, a porous bovine serum albumin (BSA) layer was first modified on the electrode surface, which can improve the position distribution and spatial orientation of the self-assembly ssDNA probe. It was then coupled with hyperbranched rolling circle amplification to develop the high-reproducibility-and-sensitivity ECL biosensor for human papillomavirus 16 E6 and E7 oncogene detection. In the presence of the target DNA, the surface of the electrode accumulates abundant amplified products through reaction, which contain double-stranded DNA (dsDNA) fragments of different lengths, followed by plentiful dichlorotris (1,10-phenanthroline) ruthenium(II) hydrate (Ru(phen)32+, acting as an ECL indicator) insertion into grooves of dsDNA fragments, and a strong signal can be detected. There is a linear relationship between the signal and the target concentration range from 10 fM to 15 pM, and the detection limit is 7.6 fM (S/N = 3). After the BSA modification step, the relative standard deviation was reduced from 9.20 to 3.96%, thereby achieving good reproducibility. The proposed ECL strategy provides a new method for constructing high-reproducibility-and-sensitivity ECL biosensors.

[Retracted] MicroRNA­21 increases cell viability and suppresses cellular apoptosis in non­small cell lung cancer by regulating the PI3K/Akt signaling pathway.

Following the publication of this paper, the authors have contacted the Editorial Office to request that their article be retracted. The reason for this retraction is an inability to be able to replicate certain of their previous results, and also disagreements among the authors as to the interpretation of some of the data. Following further discussion, all authors and the Editor of Molecular Medicine Reports are in agreement that the paper should be retracted; moreover, the authors apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 6506­6511, 2017; DOI: 10.3892/mmr.2017.7440].