Association between Epstein-Barr virus infection and serum positivity rate of anti-nuclear antibodies in Chongqing, China: A cross-sectional observational study.

Epstein-Barr virus (EBV) infects over 95% of the global population and is strongly associated with various autoimmune diseases. Anti-nuclear antibodies (ANA) serve as valuable laboratory biomarkers for screening and supporting the diagnosis of various autoimmune diseases. The aim of this study was to assess the prevalence of EBV infection and its association with ANA. This retrospective study employed standard indirect immunofluorescence assay to determine ANA levels, EBV-specific immunofluorescence assay, or plasma EBV-DNA testing. Demographic data including gender and age were collected to observe variations in EBV infection status and ANA positivity rates among different populations. Incorporating 6492 hospitalized patients who underwent ANA antibody spectrum testing, it was observed that serum positivity rates gradually increased with age. The overall serum positivity rate of ANA in females (25.14%) was significantly higher than that in males (13.76%). Among hospitalized patients undergoing EBV-DNA testing, adults aged 21 to 40 years were least affected by EBV, with a positivity rate of 11.96%; however, as age increased, the positivity rate gradually increased. Among the 5225 patients undergoing EBV antibody spectrum testing, ANA-positive patients exhibited significantly higher serum positivity rates for Epstein-Barr nuclear antigen 1 immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin A, and Epstein-Barr virus viral capsid antigen immunoglobulin A antibodies compared to ANA-negative patients (P < .001; P < .001; P = .013; P < .001). The EBV-DNA positivity rate in ANA-positive patients was also significantly higher than in ANA-negative patients, yielding the same conclusion (P = .012). The positivity rates of ANA antibodies in patients with past EBV infection and reactivation were significantly higher than those in uninfected patients (P < .001; P = .006). The positivity rate of ANA antibodies in reactivated patients was significantly higher than that in primary infected patients and those with past infections (P < .001; P < .001). Among ANA-positive patients, the positivity rates of EBV antibody spectrum and EBV-DNA were higher compared to ANA-negative patients. The positivity rates of ANA in patients with past EBV infection and reactivation were higher than those in uninfected patients.

Visualization of cysteine in AD mouse with a high-quantum yield NIR fluorescent probe.

Alzheimer's disease (AD) has gradually received enthusiastic attention with the aging process, and studying its biological relevance is expected. Excitingly, fluorescence probes were considered to be powerful tools for exploring biological correlations. Therefore, a highly selective near-infrared (NIR) fluorescent probe (DCM-Cl-Acr) for imaging cysteine (Cys) in AD was designed and synthesized. Through structural optimization, the probe exhibited high fluorescence quantum yield and low detection limit (20 nM) towards Cys. Meanwhile, based on the high selectivity and high sensitivity response exhibited by the probe to Cys, it was successfully applied to visualize endogenous and exogenous Cys in living cells and zebrafish, and showed good discrimination from homocysteine (Hcy) and glutathione (GSH). Further, the correlation between AD and Cys concentration was clarified by imaging studies in hippocampus tissue of AD mouse, and the abnormal accumulation of Cys in the hippocampus of AD brain was demonstrated.

Patient-specific 3D-printed Brace for Adolescent Idiopathic Scoliosis: A Prospective Cohort Study.

OBJECTIVE: To evaluate the efficacy and safety of patient-tailored 3D printed brace in the treatment of adolescent idiopathic scoliosis (AIS), and to compare the health-related quality of life (HRQoL) of patients treated with 2 different types of brace. MATERIALS AND METHODS: From September 2017 to August 2020, 103 AIS patients requiring non-operative management were prospectively recruited in this study. All patients were followed up every 6 months, clinical and radiologic examination were assessed at each follow-up time. Full-length anteroposterior radiographs of the spine in the standing position were obtained. At the last follow-up, each patient completed a standardized HRQoL questionnaire. Compliance is defined as that the patient insists on wearing the brace for ≥23 hours every day (full-time wearing) and follow-up every 6 months until bone maturity. The rate of major curve Cobb progression was defined that maximum Cobb angle of major curve greater than 6° compared with that at the initial diagnosis, or aggravated to more than 45° so that orthopedic surgery was recommended during treatment, which was defined as the rate of conversion to surgery. The effects of these 2 types of braces on the rate of major curve Cobb progression and HRQoL were analyzed by independent sample t test and χ2 test. RESULTS: The thickness was 4 mm for thoracolumbosacral orthosis (TLSO) and 3 mm for 3D-printed brace (3DPB). In addition, compared with the material used in TLSO, the weight (600-800 g) of the 3DPB materials with the same area is reduced by about 25% to 30%. In our sample, 55 patients (49.1%) and 48 patients (33.1%) were respectively included in the 3DPB cohort and the TLSO cohort. The maximum Cobb angle of major curve in the 3DPB cohort was significantly lower than those in the TLSO cohort at 6 months, 12 months, and the last follow-up (P < 0.01). The thoracic kyphosis (TK) and lumbar lordosis (LL) of the 2 cohorts at the last follow-up were lower than those before brace treatment, in addition, there was a significant difference in TK (P = 0.001) and LL (P = 0.004) between the 2 cohorts at the follow-up. The scores of physical function, pain, self-image, mental health, and treatment satisfaction in the Chinese version of the 22-item questionnaire of the Scoliosis Research Society in the 3DPB cohort were higher than those in the TLSO cohort (P < 0.01 and P < 0.05, respectively). The scores of the 3DPB cohort were significantly higher than those of the TLSO group in the 4 dimensions (P = 0.008, 0.013, 0.015, and 0.002, respectively) of the EuroQol-5D health description system except for mobility, and the overall health status of EuroQol-5D was higher for the 3DPB cohort (P < 0.001). At the last follow-up, 1 patient in the 3DPB cohort and 10 patients in the TLSO cohort had major curve Cobb progression of greater than 6°, and the rate of major curve Cobb progression in the 3DPB cohort was significantly lower than that in the TLSO cohort (OR 14.2, 95% CI 1.7∼115.8, P < 0.01). One patient in the 3DPB and 7 patients in the TLSO cohorts received subsequent surgery or were recommended for surgery, and the rate of conversion to surgery was significantly lower than in the 3DPB cohort (OR 9.2, 95% CI 1.1∼77.9, P < 0.05). CONCLUSIONS: A patient-tailored 3D-printed brace is lighter, thinner, and more comfortable than conventional braces in the treatment of AIS. It can substantially improve the HRQoL of patients and can significantly reduce the progression of major curve Cobb progression and rate of conversion of surgery.

Surface-mediated fluorescent sensor array for identification of gut microbiota and monitoring of colorectal cancer.

The development of efficient, accurate, and high-throughput technology for gut microbiota sensing holds great promise in the maintenance of health and the treatment of diseases. Herein, we developed a rapid fluorescent sensor array based on surface-engineered silver nanoparticles (AgNPs) and vancomycin-modified gold nanoclusters (AuNCs@Van) for gut microbiota sensing. By controlling the surface of AgNPs, the recognition ability of the sensor can be effectively improved. The sensor array was used to successfully discriminate six gut-derived bacteria, including probiotics, neutral, and pathogenic bacteria and even their mixtures. Significantly, the sensing system has also been successfully applied to classify healthy individuals and colorectal cancer (CRC) patients rapidly and accurately within 30 min, demonstrating its clinically relevant specificity.

NPAS2 dampens chemo-sensitivity of lung adenocarcinoma cells by enhancing DNA damage repair.

Chemotherapeutic agents, including cisplatin, have remained a cornerstone of lung adenocarcinoma (LUAD) treatment and continue to play an essential role in clinical practice, despite remarkable progress in therapeutic strategies. Hence, a thorough comprehension of the molecular mechanisms underlying chemotherapeutic agent resistance is paramount. Our investigation centered on the potential involvement of the NPAS2 gene in LUAD, which is highly expressed in tumors and its high expression has been associated with unfavorable overall survival rates in patients. Intriguingly, we observed that the depletion of NPAS2 in LUAD cells resulted in increased susceptibility to cisplatin treatment. Furthermore, mRNA sequencing analysis revealed that NPAS2 deficiency downregulated genes crucial to DNA repair. Additionally, NPAS2 depletion significantly impairs γH2AX accumulation, a pivotal component of the DNA damage response. Further investigation demonstrates that NPAS2 plays a crucial role in DNA double-strand breakage repair via homology-directed repair (HDR). Our inquiry into the molecular mechanisms underlying NPAS2 regulation of DDR revealed that it may enhance the stability of H2AX mRNA by binding to its mRNA, thereby upregulating the DNA damage repair pathway. In-vivo experiments further confirmed the crucial role of NPAS2 in modulating the effect of cisplatin in LUAD. Taken together, our findings suggest that NPAS2 binds to and enhances the stability of H2AX mRNA, thereby decreasing the sensitivity of tumor cells to chemotherapy by augmenting DNA damage repair.

Boronic Acid-Decorated Carbon Dot-Based Semiselective Multichannel Sensor Array for Cytokine Discrimination and Oral Cancer Diagnosis.

Cytokines are essential components of the immune system and are recognized as significant biomarkers. However, detection of a single cytokine is not precise and reliable enough to satisfy the requirements for diagnosis. Herein, we developed a pattern recognition-based method for the multiplexed sensing of cytokines, which involves three-color-emitting boronic acid-decorated carbon dots (BCDs) and arginine-modified titanium carbide (Ti3C2 MXenes) as the sensor array. Initially, the fluorescence signals of the three BCDs were quenched by Ti3C2 MXenes. In the presence of cytokines, the fluorescence intensity of the BCDs was restored or further quenched by different cytokines. The fluorescence response occurs in two steps: first, boronic acid interacts with cis-diol functional groups of cytokines, and second, arginine headgroup selectively interacts with glycans. By exploiting the different competing binding of the BCDs and the cytokines toward Ti3C2 MXenes, seven cytokines and their mixtures can be effectively discriminated at a concentration of 20 ng mL-1. Furthermore, our sensor array demonstrated an excellent performance in classifying human oral cancer saliva samples from healthy individuals with clinically relevant specificity. The noninvasive method offers a rapid approach to cytokine analysis, benefiting early and timely clinical diagnosis and treatment.

A sensitive electrochemical sensor for glutathione based on specific recognition induced collapse of silver-contained metal organic frameworks.

An electrochemical sensor capable of detecting glutathione (GSH) with high sensitivity and selectivity was developed based on the unique novel electroactive silver-based metal organic framework (Ag-MOF). The Ag-MOF obtained by silver nitrate and 1,3,5-benzoic acid (H3BTC) was thoroughly characterized and was modified onto the electrode via facile drop-casting method. The electrochemical response of GSH on the Ag-MOF modified electrode showed a significant reduction in the current signal because the Ag-GSH complex had stronger specific affinity than Ag-H3BTC and resulted in the collapse of the Ag-MOF. This sensor demonstrated an extensive linear dynamic range of 0.1 nM-1 µM, along with the low detection limit of 0.018 nM. Additionally, it exhibited good reproducibility, stability, and resistance to interfering compounds. The Ag-MOF modified electrode demonstrated superior performance attributed to its rapid electron transfer rate, outstanding electrochemical redox activity, and specific recognition/competitive reaction. These factors improved both sensitivity and selectivity. The high anti-interference ability allowed for the selective detection of GSH in intricate surroundings. In the real sample testing, the RSD was lower than 3.1% and the recovery was between 98.1 and 103%. This research highlights the potential of Ag-MOFs in developing electrochemical sensors and their promising applications in determining GSH for food screening and early disease diagnosis.

DNA Sensor-Based Strategy to Visualize the TRPM7 mRNA-Mg2+ Signaling Pathway in Cancer Cells.

Technological advances and methodological innovations in cell signaling pathway analysis will facilitate progress in understanding biological processes, intervening in diseases, and screening drugs. In this work, an elaborate strategy for visualizing and monitoring the transient receptor potential melastatin 7 (TRPM7)-Mg2+ signaling pathway in living cells was constructed through the logical analysis of upstream mRNA and downstream molecules by two individual DNA sensors. The DNA sensors are constructed by modifying the dye-labeled DNA sequences on the surface of gold nanoparticles. By hybridizing with upstream mRNA, Cy5-modified DNA sensor 1 can detect and silence it simultaneously, outputting a red fluorescence signal. When the upstream mRNA is silenced, the concentration of downstream molecules of Mg2+ will be affected and down-regulated. The FAM-modified DNA sensor 2 detects this change and emits a green fluorescence as a signal. Therefore, the dynamic information on TRPM7 mRNA and the Mg2+-mediated signaling pathway can be successfully obtained by fluorescence imaging methods. Furthermore, the TRPM7 mRNA-Mg2+ signaling pathway also affects cell activity and migratory function through cell scratching and other experiments. More importantly, the proposed sensor also shows potential for screening signaling pathway inhibitors. Our work provides a simple and general strategy for the visualization of signaling pathways, which helps to understand the changes in the physiological activities of cancer cells and the causes of carcinogenesis and is crucial for cancer diagnosis and prognosis.

Consuming intracellular glucose and regulating the levels of O2/H2O2 via the closed cascade catalysis system of Cu-CeO2 nanozyme and glucose oxidase.

Imbalances in the intracellular environment caused by high levels of glucose, H2O2, and hypoxia can greatly impact cancer development and treatment. However, there is limited research on regulating the levels of these species simultaneously in tumor cells. Here, a pH-responsive nanozyme-enzyme hybrid system was developed to regulate intracellular glucose, H2O2 and O2. The system, named DMSN@Cu-CeO2@GOx, consists of Cu-CeO2 nanoparticles and glucose oxidase (GOx) immobilized in dendritic mesoporous silica (DMSN) spheres. GOx efficiently consumes glucose in tumor cells, causing a drop in pH and producing a significant amount of H2O2. Cu-CeO2 then catalyzes the conversion of H2O2 to O2 due to its high catalase-like (CAT) activity in weakly acidic conditions. The process was monitored by fluorescence probes, and the mechanism was investigated through fluorescence spectroscopy and confocal laser scanning microscopy. The cascade catalytic system with excellent biocompatibility continuously consumes glucose and elevates the level of O2 in cells. This hybrid nanomaterial offers a means to regulate the glucose/H2O2/O2 levels in cells and may provide insights into starvation therapy by modulating reactive species within cells.

Molecular dynamic simulation reveals the molecular interactions of epidermal growth factor receptor with musk xylene are involved in the carcinogenicity.

Musk xylene (MX), a kind of personal care product, has become a new type of environmental contaminant in recent years. Long-term exposure to MX is associated with a variety of cancers, but the mechanism is still unclear. Meanwhile, our previous research showed that MX exposure could lead to malignant transformation of human liver cells L02 and up-regulation of multi genes which are involved in the MAPK signaling pathway, such as the epidermal growth factor receptor (EGFR). These findings indicated that the MAPK signaling pathway might be involved in the malignant transformation caused by MX, but the mechanism is also unclear. In this study, the underlying interaction mechanisms between EGFR and MX were investigated using molecular dynamics (MD) simulation. Results revealed that MX bound to the ECD of EGFR in four binding sites, which was mainly driven by van der Waals and nonpolar interactions, and the affinity of MX toward ECD was sIII > sI > sII > sIV. Further analysis through MD simulation found that s III, the site with the strongest binding, was coincidentally located at the binding area of EGF, which is the natural ligand of EGFR. Therefore, we speculated that MX may activate the MAPK signaling pathway by binding to EGFR in a similar way to EGF, and finally lead to tumorigenesis. In addition, the MM/PBSA method could also be utilized to calculate the hot residues in each binding site. The prediction of hot residues would provide some theoretical guidance for further study of the carcinogenesis mechanisms of MX both in MD simulation and experimental research.

General Strategy for Specific Fluorescence Imaging of Homocysteine in Living Cells and In Vivo.

The aberrantly changed level of homocysteine (Hcy) triggers a variety of pathological symptoms and subsequently Hcy-related diseases. Direct and selective visualization of Hcy in biological systems is pivotal to understanding the pathological functions of Hcy at the molecular level. Herein, a general strategy was developed for the specific fluorescence imaging of Hcy through the combination of dual-binding sites and the introduction of a nitro group at the 6-position of the 7-diethylaminocoumarin fluorophore. Also, a series of novel fluorescent probes were exploited for monitoring Hcy with excellent selectivity, high sensitivity, and far-red/near-infrared fluorescence emission. Furthermore, fluorescence imaging of endogenous Hcy dynamics in living cells and in vivo was achieved, providing direct and solid evidence for the increasement of endogenous Hcy in type 2 diabetes mellitus and Alzheimer's disease. This research will greatly advance the development and understanding of the molecular nexus between the Hcy metabolism cascade and the root causes of diseases related to Hcy.

Recognition Engineering-Mediated Multichannel Sensor Array for Gut Microbiota Sensing.

The composition and activity of the gut microbiota are crucial for health management and disease treatment. Herein, we develop a rapid and robust multichannel sensor array via a recognition engineering strategy using antimicrobial agent (vancomycin, bacitracin, and lysozyme) functional gold nanoclusters and gluconamide-modified Ti3C2 MXenes, which provide superior fingerprint patterns to distinguish gut-derived bacteria. The discrimination ability of the sensor array was highly improved via the synergistic recognition between the bacteria and the various antimicrobial agents. Five gut-derived bacteria, including probiotics, neutral, and pathogenic bacteria were clearly differentiated and discriminated from the bacteria mixtures. Furthermore, the sensing system was successfully applied for the accurate classification of human colorectal cancer samples from healthy individuals rapidly (30 min) with clinically relevant specificity. The rapidity, simplicity, and economic cost of this strategy offers a robust platform for gut microbiota analysis.

Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma.

BACKGROUND: Cuproptosis is a new type of copper-induced cell death that is characterized by the aggregation of lipoylated tricarboxylic acid (TCA) cycle proteins. However, its role in hepatocellular carcinoma (HCC) remains unclear. The goal of this research is to develop a cuproptosis-related signature predicting the prognosis of HCC. METHODS: The cuproptosis-related genes were defined using Pearson correlation coefficients. LASSO-Cox regression analysis was used to evaluate the prognostic values of cuproptosis-related genes to construct a cuproptosis-related prognostic model. The immune microenvironment analysis was performed by "ssGSEA" to reveal the associated immune cell infiltration patterns with the cuproptosis-related genes signature. The expression levels of one of the prognostic genes PDXK were then verified in HCC samples by Western Blot and immunohistochemistry. The potential roles of target genes in cuproptosis were further explored during in-vitro experiments. RESULTS: A total of 136 cuproptosis-related genes were discovered using Pearson correlation analysis in HCC. A cuproptosis-related signature that included 5 cuproptosis-related genes (PDXK, HPN, SLC25A28, RNFT1, CLEC3B) was established in the TCGA-LIHC training cohort. TCGA validation cohort and another two external validation cohorts confirmed the robustness of the signature's predictive value. Moreover, a nomogram using the risk score was created to best predict the survival of HCC patients. The immune microenvironment analysis revealed distinct immune infiltrations patterns between different risk groups based on the signature model. Furthermore, the upregulation of PDXK was confirmed in HCC tumor tissues in 30 clinical HCC specimens. The knockdown of PDXK reduced the proliferation, migration and invasion of HCC cells. Besides, the expression of PDXK was upregulated after the induction of cuproptosis by elesclomol-CuCL2, which could be suppressed when pretreated with a copper ion chelator. And PDXK deficiency increased the sensitivity of HCC cells to cuproptosis inducer. CONCLUSION: Our study identified a new cuproptosis-related gene signature that could predict the prognosis of HCC patient. Besides, the upregulated PDXK could promote the proliferation and metastasis of HCC. And PDXK deficiency facilities cuproptosis in HCC. Therefore, these fundings highlighted that PDXK might serve as a potential diagnostic and therapeutic target for HCC.

Insulin-like growth factor-2 mRNA-binding protein 3 promotes cell migration, invasion, and epithelial-mesenchymal transition of esophageal squamous cell carcinoma cells by targeting zinc finger E-box-binding homeobox 1 mRNA.

The role and mechanism of insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) in the metastasis of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, IGF2BP3 mRNA and protein expression levels were evaluated in ESCC tissues. Small interfering RNAs (siRNAs), plasmid overexpression, and stable lentivirus transfection were used to manipulate intracellular IGF2BP3 expression levels. The role of IGF2BP3 in ESCC tumorigenesis was investigated in vitro and in vivo. IGF2BP3 target transcripts were detected, and the acetylation effect ratios of the IGF2BP3 promoter region by H3K27ac were determined. IGF2BP3 mRNA expression levels were significantly higher in ESCC tissues than in normal esophageal tissues. Increased IGF2BP3 expression levels were detected in node-negative ESCC tissues and correlated with greater lesion depth in ESCC. Overexpression of IGF2BP3 promoted ESCC development in vitro and in vivo, and IGF2BP3 knockdown caused an opposite effect. IGF2BP3 was found to directly bind to the zinc finger E-box-binding homeobox 1 (Zeb1) mRNA, and the downregulation of IGF2BP3 reduced the stability of Zeb1 mRNA. IGF2BP3 induced epithelial-mesenchymal transition in ESCC cells in a Zeb1-dependent manner. IGF2BP3 was transcriptionally activated in ESCC cell lines via H3K27 acetylation. Our results demonstrate that IGF2BP3 plays a vital role in ESCC cell proliferation, invasion, and metastasis and is a potential therapeutic target for treating ESCC.

Identification and validation of a novel cuproptosis-related signature as a prognostic model for lung adenocarcinoma.

Background: Cuproptosis is a novel form of copper-induced cell death that targets lipoylated tricarboxylic acid (TCA) cycle proteins. However, its prognostic role in lung adenocarcinoma (LUAD) remains unclear. This study aimed to establish a cuproptosis-related prognostic signature for patients with LUAD. Methods: Transcriptome data of LUAD samples were extracted from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic value of cuproptosis-related genes (CRGs) was investigated using Cox regression analysis to develop a cuproptosis-related prognostic model. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO) and gene set variation analysis (GSVA) were conducted to characterize different biological activities or pathways between high- or low-CRG groups. The expression pattern and prognostic values of CRGs were validated in 37 paired tumor-normal samples using quantitative PCR. Furthermore, in vitro experiments were performed to investigate the relationship between cuproptosis and CRG expression and to explore the function of target genes in cuproptosis. Results: Among the 36 CRGs, 17 genes were upregulated, and 3 genes were downregulated in LUAD. A total of 385 CRGs were identified using Pearson correlation analysis. A cuproptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) analysis. The prognostic value of the cuproptosis-related signature was validated in six external validation cohorts and in LUAD specimens from our facility. Patients in the high-risk group based on the CRG signature score had shorter overall survival than those in the low-risk group in both the datasets and clinical specimens. In vitro experiments revealed that the expression of BARX1, GFRA3, and KHDRBS2 was upregulated after cuproptosis was induced by elesclomol-CuCL2, whereas the upregulation was suppressed on pretreatment with tetrathiomolybdate (TTM), a chelator of copper. Further, the cell proliferation assay revealed that the BARX1 and GFRA3 deficiency facilities the cuproptosis induced by elesclomol-CuCL2. Conclusion: This study established a new CRG signature that can be used to predict the OS of LUAD patients. Moreover, the knockdown of BARX1 and GFRA3 could increase the sensitivity of LUAD cells to the cuproptosis.

Self-Cascade Nanoenzyme of Cupric Oxide Nanoparticles (CuO NPs) Induced in Situ Catalysis Formation of Polyelectrolyte as Template for the Synthesis of Near-Infrared Fluorescent Silver Nanoclusters and the Application in Glutathione Detection and Bioimaging.

In this work, near-infrared fluorescent silver nanoclusters (Ag NCs) were prepared based on the in situ formed poly methacrylic acid (PMAA) as the template and stabilizer, which is synthesized by methacrylic acid (MAA) and hydroxyl radical (·OH) that is generated by the cascade nanoenzyme reaction of cupric oxide nanoparticles (CuO NPs). CuO NPs possess the intrinsic glutathione-like (GPx-like) and peroxidase-like (POD-like) activities, which can catalyze glutathione (GSH) and O2 to produce hydrogen peroxide (H2O2), and then transform into ·OH. The fluorescence intensity of Ag NCs decreases with the addition of GSH, because the -SH can easily anchor on the surface, resulting in the PMAA leaving the Ag NCs, and the coeffect of GSH and PMAA results in the aggregation to form larger Ag NPs. A good linear relationship between the fluorescence quenching rate and the GSH concentration was found in the range 0.01-40 µM with the detection limit 8.0 nM. The Ag NCs can be applied in the detection of GSH in the serum, as well as bioimaging of endogenous and exogenous GSH in cells with high sensitivity. Moreover, the normal and cancer cells can be distinguished through bioimaging because of the different GSH levels. The new method for the preparation of biocompatible nanoprobe based on the nanozyme tandem catalysis and the in situ formed template can avoid the direct usage of polymers or protein templates that hinder preparation and separation, providing a reliable approach for the synthesis, biosensing, and bioimaging of nanoclusters.

Picomolar glutathione detection based on the dual-signal self-calibration electrochemical sensor of ferrocene-functionalized copper metal-organic framework via solid-state electrochemistry of cuprous chloride.

Chemical biosensing techniques are essential for food analysis and disease diagnosis. Nanomaterials with redox activity show great potential in electrochemical analysis, acting as signal labels or signal amplification unit, which can reflect the targets concentration in foods and biological samples. Here, an ultra-sensitive dual-signal intrinsic self-calibration electrochemical platform for GSH was firstly fabricated based on the novel electroactive nanomaterial of ferrocene-functionalized copper metal-organic framework (Fc-Cu-MOF). Due to the solid-state electrochemical property of cuprous chloride (CuCl), a sharp characteristic peak with an increased signal appears with the coexistence of chloride ions in solution. The stronger specific affinity between Cu+ and GSH than that of Cu+ and Cl- triggers a "crowding effect" that causes the current signal of CuCl decrease greatly. Meanwhile, the peak current of ferrocene keeps unchanged as an internal reference. Based on the ratio of the peak current variation (ΔICu/ΔIFc) as the signal output, Fc-Cu-MOF modified electrode showed wider linear range in 0.1 nM -1 µM for GSH with the detection limit as low as 0.025 nM. And the sensor was successfully applied in the determination of GSH with excellent recoveries in various real samples such as food and serum samples, providing good prospect in application of bioanalysis and food screening.

Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells.

Both tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine can be metabolized by cytochrome P450 2A13 (CYP2A13). Previous studies have shown that nicotine has a potential inhibitory effect on the toxicity of NNK. However, due to the lack of CYP2A13 activity in conventional lung cell lines, there had been no systematic in vitro investigation for the key target organ, the lung. Here, BEAS-2B cells stably expressing CYP2A13 (B-2A13 cells) were constructed to investigate the effects of nicotine on the cytotoxicity and genotoxicity of NNK. The results showed more sensitivity for NNK-induced cytotoxicity in B-2A13 cells than in BEAS-2B and B-vector cells. NNK significantly induced DNA damage, cell cycle arrest, and chromosomal damage in B-2A13 cells, but had no significant effect on BEAS-2B cells and the vector control cells. The combination of different concentration gradient of nicotine without cytotoxic effects and a single concentration of NNK reduced or even counteracted the cytotoxicity and multi-dimensional genotoxicity in a dose-dependent manner. In conclusion, CYP2A13 caused the cytotoxicity and genotoxicity of NNK in BEAS-2B cells, and the addition of nicotine could inhibit the toxicity of NNK.

Signal On-Off Electrochemical Sensor for Glutathione Based on a AuCu-Decorated Zr-Containing Metal-Organic Framework via Solid-State Electrochemistry of Cuprous Chloride.

A novel signal on-off glutathione (GSH) electrochemical sensor was developed based on a AuCu bimetal-decorated Zr-containing metal-organic framework (Zr-MOF), in which a signal amplification strategy promoted by solid-state electrochemistry of cuprous chloride (CuCl) was used. The Zr-MOF with a large surface area can be effectively used as the substrate for the in situ growth of AuCu bimetals to obtain the Zr-MOF@AuCu nanocomposite. The interaction between Cu in Zr-MOF@AuCu and Cl- in the solution accompanied with the formation of CuCl displays an enlarged stable oxidation current, which greatly declines with the addition of GSH owing to the specific Cu-GSH interaction. The conversion of CuCl into Cu-GSH triggered the "crowding-out effect" and resulted in a sharp drop in the peak current of CuCl, which can realize the ultrasensitive and selective detection of GSH. The detection mechanism was investigated, and the detection range was 10 pM-1 mM with the detection limit as low as 2.67 pM. The special response mechanism for the detection of GSH allows the highly selective detection of GSH in various real samples with reliable results, endowing the proposed electroanalysis sensor with broad application prospects in biological and food analysis.

From part to whole, operative link on to endoscopic grading of gastric intestinal metaplasia, pathology to endoscopy: gastric intestinal metaplasia graded by endoscopy.

Objective: To conduct a systematic review and meta-analysis on the prediction of severity of gastric intestinal metaplasia (GIM) in localized and entire gastric mucosa using endoscopy. Methods: The authors searched Web of Science, PubMed, Embase and Cochrane Central Register of Controlled Trials and performed systematic searches on endoscopic grading of GIM of the entire stomach using Meta-DiSc and Stata. Results: Sensitivity and specificity for the stratified prediction of overall GIM were 0.91 (95% CI: 0.85-0.95) and 0.91 (95% CI: 0.88-0.93), respectively. Sensitivity in predicting the different grades of GIM was higher in operative link on GIM assessment grades 0, III and IV but lower in grades I and II. Conclusion: Digital chromoendoscopy is well suited to predicting the severity of localized and overall GIM.