Recognition of rare antinuclear antibody patterns based on a novel attention-based enhancement framework.

Rare antinuclear antibody (ANA) pattern recognition has been a widely applied technology for routine ANA screening in clinical laboratories. In recent years, the application of deep learning methods in recognizing ANA patterns has witnessed remarkable advancements. However, the majority of studies in this field have primarily focused on the classification of the most common ANA patterns, while another subset has concentrated on the detection of mitotic metaphase cells. To date, no prior research has been specifically dedicated to the identification of rare ANA patterns. In the present paper, we introduce a novel attention-based enhancement framework, which was designed for the recognition of rare ANA patterns in ANA-indirect immunofluorescence images. More specifically, we selected the algorithm with the best performance as our target detection network by conducting comparative experiments. We then further developed and enhanced the chosen algorithm through a series of optimizations. Then, attention mechanism was introduced to facilitate neural networks in expediting the learning process, extracting more essential and distinctive features for the target features that belong to the specific patterns. The proposed approach has helped to obtained high precision rate of 86.40%, 82.75% recall, 84.24% F1 score and 84.64% mean average precision for a 9-category rare ANA pattern detection task on our dataset. Finally, we evaluated the potential of the model as medical technologist assistant and observed that the technologist's performance improved after referring to the results of the model prediction. These promising results highlighted its potential as an efficient and reliable tool to assist medical technologists in their clinical practice.

Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFß signaling.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

Development of a scoring system for predicting the severity of ulcerative colitis.

BACKGROUND AND STUDY AIMS: Monitoring disease activity in ulcerative colitis (UC) is critical in preventing long-term complications. This study aims to develop a scoring system using non-invasive indicators to predict endoscopic activities for ulcerative colitis (UC) patients. PATIENTS AND METHODS: All enrolled patients with UC admitted to Shanghai Xinhua Hospital between June 2017 and January 2021 were enrolled, and their clinical data were retrospectively collected and a number of serological biomarkers concentrations were analyzed. Patients were categorized into mild and moderate-to-severe disease groups. Univariate and multivariate logistic regression was used to predict moderate-to-severe endoscopic activities, which were then incorporated into a nomogram to establish a prediction scoring model. RESULT: Overall, 231 patients were divided into a mild group (n = 111, 48.0%) and a moderate-to-severe group (n = 120, 52.0%). The following variables were independently associated with the disease severity and were subsequently included into the prediction model: Proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA), C-reactive protein (CRP), hemoglobin(Hb), IL-10, stool frequency ≥ 5 times/day and hematochezia. Incorporating these 6 factors, the nomogram showed good discrimination with C-index of 0.819 and reliable calibration. A scoring model was established with the area under the curve 0.818. Moreover, PR3-ANCA and CRP correlated with the duration of hospital stay. CONCLUSION: We developed a predictive model for endoscopic disease activities by using noninvasive factors based on PR3-ANCA, CRP, Hb, IL-10, stool frequency and hematochezia. This prediction model might assist clinicians in managing patients with UC.

Intermittent hypoxia inhibits anti-tumor immune response via regulating PD-L1 expression in lung cancer cells and tumor-associated macrophages.

Accumulating evidence has shown an increased tumor incidence and reduced survival rate in cancer patients with obstructive sleep apnea (OSA). Although intermittent hypoxia is known to play a crucial role, the molecular mechanism by which intermittent hypoxia accelerates lung cancer progression remains to be elucidated.A lung cancer xenograft mouse model was established by subcutaneously injecting LLC cells into C57BL/6 mice. The tumor-bearing mice were exposed to either normoxia or intermittent hypoxia and received either IgG2a, anti-programmed death ligand-1 (PD-L1), PX-478, or anti-PD-L1 + PX-478 treatment.A significant upregulation of tumor associated macrophages (TAMs) papulation and PD-L1 levels was observed in lung adenocarcinoma patients with OSA. We further confirmed that hypoxia-inducible factor-1 alpha (HIF-1α) regulates PD-L1 at transcriptional levels, mainly through binding to the hypoxia response element 4. Using a lung cancer xenograft mouse model, we observed that intermittent hypoxia exposed tumors grew faster and bigger with upregulated HIF-1α and PD-L1 expression, enhanced TAMs and Treg populations, and reduced cytotoxic T cells and cytokine secretion. Finally, we found a combination of PX-478 and anti-PD-L1 exerted an encouraging tumor inhibition effect compared to single treatment. Combination therapies based on HIF-1α and PD-L1 blockade might serve as a promising strategy to treat lung cancer patients with OSA.

The Role of TSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical Target.

Atopic dermatitis (AD) is a kind of chronic skin disease with inflammatory infiltration, characterized by skin barrier dysfunction, immune response dysregulation, and skin dysbiosis. Thymic stromal lymphopoietin (TSLP) acts as a regulator of immune response, positively associated with AD deterioration. Mainly secreted by keratinocytes, TSLP interacts with multiple immune cells (including dendritic cells, T cells, and mast cells), following induction of Th2-oriented immune response during the pathogenesis of AD. This article primarily focuses on the TSLP biological function, the relationship between TSLP and different cell populations, and the AD treatments targeting TSLP.

Multispectral camouflage nanostructure design based on a particle swarm optimization algorithm for color camouflage, infrared camouflage, laser stealth, and heat dissipation.

With the development of camouflage technology, single camouflage technology can no longer adapt to existing environments, and multispectral camouflage has attracted much research focus. However, achieving camouflage compatibility across different bands remains challenging. This study proposes a multispectral camouflage metamaterial structure using a particle swarm optimization algorithm, which exhibits multifunctional compatibility in the visible and infrared bands. In the visible band, the light absorption rate of the metamaterial structure exceeds 90%. In addition, color camouflage can be achieved by modifying the top cylindrical nanostructure to display different colors. In the infrared band, the metamaterial structure can achieve three functions: dual-band infrared camouflage (3-5 µm and 8-14 µm), laser stealth (1.06, 1.55, and 10.6 µm), and heat dissipation (5-8 µm). This structure exhibits lower emissivity in both the 3-5-µm (ɛ=0.18) and 8-14-µm (ɛ=0.27) bands, effectively reducing the emissivity in the atmospheric window band. The structure has an absorption rate of 99.7%, 95.5%, and 95% for 1.06, 1.55, and 10.6 µm laser wavelengths, respectively. Owing to its high absorptivity, laser stealth is achieved. Simultaneously, considering the heat dissipation requirements of metamaterial structures, the structural emissivity is 0.7 in the non-atmospheric window (5-8 µm), and the heat can be dissipated through air convection. Therefore, the designed metamaterial structure can be used in military camouflage and industrial applications.

D-Mannose ameliorates DNCB-induced atopic dermatitis in mice and TNF-α-induced inflammation in human keratinocytes via mTOR/NF-κB pathway.

D-mannose is a C-2 epimer of glucose, widely distributed in nature. Atopic dermatitis (AD) is a chronic inflammatory disease characterized by repetitious itching. The present study aimed to explore the protective effect and the underlying mechanism of D-mannose against the development of atopic dermatitis. We tested the effect of D-mannose by establishing DNCB (2,4-dinitrochlorobenzene)-induced AD mice models in vivo and culturing keratinocytes (HaCaT and NHEK) in vitro. The skin lesion severity was evaluated by histochemical staining. Cytokine expression levels were measured by real-time PCR and ELISA assay. The expression of the mammalian target of rapamycin (mTOR)/ nuclear transcription factor κB (NF-κB)-signaling-related molecules were determined by western blotting. Here, we found that topical supplementation of D-mannose remarkably attenuated skin lesions and recovered skin barrier function in AD mice model induced by DNCB. Furthermore, in vivo and in vitro experiments indicated that D-mannose inhibited tumor necrosis factor-α (TNF-α)-mediated increased expression of inflammatory cytokines. D-mannose also markedly downregulated TNF-α-stimulated activation of mTOR/NF-κB signaling pathway that was crucial for regulating the inflammatory condition. However, these effects were abolished by treatment with inhibitors of mTOR or NF-κB in HaCaT and NHEK. As far as we know, this is the first study uncovering the effective role of D-mannose via skin topical application. We found that D-mannose plays a regulatory role on inflammatory keratinocytes, suggesting its therapeutic utilization as a potential drug against atopic dermatitis.

Lung-specific exosomes for co-delivery of CD47 blockade and cisplatin for the treatment of non-small cell lung cancer.

A cluster of differentiation 47 (CD47) and immune-modulatory protein for myeloid cells has been implicated in cisplatin (CDDP) resistance. Exosome delivery of drugs has shown great potential for targeted drug delivery in the treatment of various diseases. In the current study, we explored the approach of co-delivering CDDP and CD47 antibody with MDA-MB-231 cell-derived exosome 231-exo (CaCE) and assessed the phagocytosis activity of bone marrow flow cytometry derived macrophages (BMDM) against co-cultured A549 cells. CD8+ T-cell proliferation was examined with flow cytometry analysis. In vivo, we used the Lewis lung carcinoma (LLC) tumor-bearing mouse model and assessed survival rate, tumor weight, phagocytosis, and T-cell proliferation, as well as cytokine levels in tumors analyzed by enzyme-linked immunoassay (ELISA). Although co-administration of CDDP with anti-CD47 (CDDP and aCD47) showed a significant antitumor effect, CaCE had an even more dramatic anticancer effect in survival rate and tumor weight. We observed increased phagocytosis activity selectively against lung tumor cells in vivo and in vitro with exosome CaCE treatment. CaCE treatment also increased T-cell proliferation compared to the vehicle treatment and co-administration groups. Furthermore, immunostimulatory interleukin (IL)-12p and interferon (IFN)-γ were increased, whereas transforming growth factor ß (TGF-ß) were decreased, indicating the improved CDDP anticancer effect is related to a tumor microenvironmental change. Our study demonstrates a dramatically improved anticancer effect of CDDP when administered by exosome co-delivery with anti-CD47.

Uncovering the extensive trade-off between adaptive evolution and disease susceptibility.

Favored mutations in the human genome may make the carriers adapt to changing environments and lifestyles but also susceptible to specific diseases. The scale and details of the trade-off between adaptive evolution and disease susceptibility are unclear because most favored mutations in different populations remain unidentified. As no statistical test can discriminate favored mutations from nearby hitchhiking neutral ones, we report a deep-learning network (DeepFavored) to integrate multiple statistical tests and divide identifying favored mutations into two subtasks. We identify favored mutations in three human populations and analyzed the correlation between favored/hitchhiking mutations and genome-wide association study (GWAS) sites. Both favored and hitchhiking neutral mutations are enriched in GWAS sites with population-specific features, and the enrichment and population specificity are prominent in genes in specific Gene Ontology (GO) terms. These provide evidence for extensive and population-specific trade-offs between adaptive evolution and disease susceptibility. The unveiled scale helps understand and investigate differences and diseases of humans.

A Dual-Band Guided Laser Absorber Based on Plasmonic Resonance and Fabry-Pérot Resonance.

We numerically investigated a dual-band metamaterial absorber based on the combination of plasmonic resonance and Fabry-Pérot (FP) resonance, which can achieve near-unity absorption for guided lasers. The absorber is constructed by a three-layer metal-insulator-metal (MIM) periodic configuration. In each unit cell, there is a gold-silicon cross on a thin silicon layer and a bottom nickel film. Numerical results show that, at normal incidence, the structure strongly absorbs light at wavelengths of 1.064 µm and 10.6 µm, with absorption rates higher than 94%. It is revealed that the two absorption peaks result from FP resonance in the thin silicon layer and plasmonic resonance in the cross, respectively. In addition, the absorber is polarization insensitive and is tolerant to the incident angle. The proposed combination of different resonances has the advantage of easily producing double absorption peaks with very large wavelength differences, and provides a new approach to the design of metamaterial absorbers.

CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model.

Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8+ T cells, and cytokines (tumor growth factor (TGF)-ß, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.

Artemisinin ameliorates intestinal inflammation by skewing macrophages to the M2 phenotype and inhibiting epithelial-mesenchymal transition.

BACKGROUND: Inflammatory bowel disease (IBD) is a self-destructive intestinal disease whose etiology is unclear but complex and the effective treatment is deficient. Increasing evidences have indicated that immune dysfunction and epithelial-mesenchymal transition (EMT)-related intestinal mucosal barrier impaired hold critical position in the pathogenesis of IBD. Artemisinin (ART) is a sesquiterpenoid compound extracted from Chinese herbal medicine which has good immunomodulatory effects. Studies have shown that artemisinin and its analogues have therapeutic effects on a variety of tumors and immune-related disorders. The purpose of current study was to research the effect and mechanism about artemisinin-induced macrophage polarization to M2 phenotype and inhibiting the process of EMT. METHODS: In vitro, the anti-inflammatory effect of artemisinin is mainly verified by RAW264.7 cells and tissue (colon tissue and PBMC) from CD patients with active intestinal inflammation. RAW264.7 cells stimulated with LPS to induce inflammatory state and ART were used as therapeutic treatment in different concentration. Then the expression levels of pro-inflammatory factors, macrophage polarization and ERK pathway were analyzed. Colon tissue and PBMC from CD patients were treated with ART in different concentrations and macrophage polarization, pro-inflammatory factors expression, EMT-related protein were analyzed. In vivo, DSS-induced colitis mice were treated by ART for seven days. The DAI score was calculated and the colons and spleens were harvested after the animals were sacrificed. The expression of macrophage markers and EMT-related markers in the intestines of mice in each group were monitored by qPCR and western blot. RESULT: ART treatment could decrease the levels of pro-inflammatory coefficient expressed in theRAW264.7 cells and human PBMC. Moreover, ART could ameliorate the intestinal inflammation in vivo through down-regulating the expression of pro-inflammatory factors, promoting macrophage polarization to M2 phenotype and inhibiting the process of EMT. CONCLUSION: Taken together, our findings demonstrated that artemisinin might ameliorate inflammation by inducing macrophage polarization to M2 phenotype and inhibiting the process of EMT, suggesting that ART may be applied to the rehabilitation of IBD in the future.

Prognostic value of YKL-40 in solid tumors: a meta-analysis of 41 cohort studies.

BACKGROUND: Serum/plasma YKL-40 can be a useful index that is associated with tumor development. However, the prognostic value of serum/plasma YKL-40 in patients with solid tumors is still unclear. We aimed to utilize the existing literature to investigate the prognostic value of serum/plasma YKL-40 in solid tumors. METHODS: An extensive literature search for relevant studies was conducted with the Embase, Medline and Web of Science databases. The effect on survival was measured with the hazard ratio (HR). Then, pooled HRs and 95% confidence intervals (CIs) were calculated using the random and fixed-effects models according to the heterogeneity of the included studies. RESULTS: This meta-analysis was based on 41 publications and comprised a total of 7762 patients with solid tumors. The pooled HR showed that elevated serum/plasma YKL-40 was significantly associated with poor OS (HR, 1.44; 95% CI 1.33-1.56). We also found that elevated serum/plasma YKL-40 had significant prognostic effects on OS in various cancer subgroups such as gastrointestinal tumors (HR, 1.37; 95% CI 1.18-1.58), ovarian cancer (HR, 2.27; 95% CI 1.69-3.06), melanoma (HR, 1.77; 95% CI 1.18-2.67), lung cancer (HR, 1.73; 95% CI 1.35-2.23), urologic neoplasms (HR, 1.61; 95% CI 1.08-2.40) and glioblastoma (HR, 1.23; 95% CI 1.07-1.42); in contrast, the prognostic effect of serum/plasma YKL-40 was not statistically significant in breast cancer (HR, 1.07; 95% CI 0.98-1.17). CONCLUSIONS: The available evidence supports the hypothesis that elevated serum/plasma YKL-40 is associated with poor survival in patients with solid tumors and that serum/plasma YKL-40 may serve as a novel prognostic biomarker.

A fluorometric aptamer nanoprobe for alpha-fetoprotein by exploiting the FRET between 5-carboxyfluorescein and palladium nanoparticles.

Alpha-fetoprotein (AFP) is a reliable clinical marker of hepatocellular carcinoma (HCC). A highly sensitive fluorometric aptamer nanoprobe is described for AFP detection. It is based on fluorescence resonance energy transfer (FRET) between AFP aptamer labelled with 5-carboxyfluorescein (FAM) and palladium nanoparticles (PdNPs). The PdNPs quench the green fluorescence of the FAM-AFP aptamer via interactions between nitrogen functional groups of the AFP aptamer and PdNPs. When AFP was introduced into the FAM-AFP aptamer-PdNPs FRET system, the AFP aptamer preferentially combines with AFP. This results in a conformational change and weakens the interaction between the aptamer and the PdNPs. Thus, the fluorescence of FAM recovers. The fluorescence recovery of FAM increases linearly in the 5.0-150 ng·mL-1 AFP concentration range and has a 1.4 ng·mL-1 detection limit. The assay was applied to the analysis of spiked diluted human serum. The recovery values ranged from 98.3 to 112.9%, with relative standard deviations of <1.1%. This biosensing strategy provides a reliable and ultrasensitive protocol for the quantification of biomarkers with relevant antigens and aptamers. Graphical abstract Schematic presentation of a fluorometric aptamer nanoprobe for AFP assay based on fluorescence resonance energy transfer (FRET) between AFP aptamer labelled with 5-carboxyfluorescein (FAM) and palladium nanoparticles (PdNPs).

Efficacy of Xianling Gubao capsule in treating sarco-osteopenia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Sarco-osteopenia (SOP) is a new type of geriatric syndrome, resulting from the combination of sarcopenia (SP) and osteoporosis (OP). Xianling Gubao capsule (XLGBC), made from several traditional Chinese medicine, is reported to have a therapeutic effect on diseases of bones and joints. This protocol will be designed to assess the efficacy of XLGBC in the treatment of SOP. METHODS: Relevant randomized controlled trial literatures evaluating the effect of XLGBC on patients with SOP will be obtained by searching the following 7 electronic databases: Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical Database (CBM), and Wanfang Database, from inception to March 2019. The primary outcomes will be bone mineral density, skeletal muscle mass index, handgrip strength, and gait speed. Stata V.13.0 software will be used for data synthesis and analysis, sensitivity analysis, subgroup analysis, and risk of bias assessment. Reporting bias will be evaluated utilizing a funnel, with Egger tests assessing funnel plot symmetries. Quality of evidence will be evaluated according to guidance of the Recommendations Assessment, Development, and Evaluation guideline. RESULT: This study will provide a rational synthesis of current evidences for XLGBC on SOP. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of XLGBC on SOP. ETHICS AND DISSEMINATION: This systematic review will be contributed to peer-reviewed publications, aiming to provide evidence about efficacy of XLGBC on SOP. TRIAL REGISTRATION NUMBER: CRD42019128223.

Eugenol inhibits non-small cell lung cancer by repressing expression of NF-κB-regulated TRIM59.

In view of the recognized anti-tumor properties of eugenol against non-small cell lung cancer (NSCLC) in cell culture, here we further set out to investigate the potential therapeutic effect of eugenol in vivo and elucidate the underlying molecular mechanism. The relative expression levels of TRIM59 and p65 in NSCLC were quantified by real-time polymerase chain reaction. Xenograft tumor model was established with TRIM59-deficient H1975 cells, and tumor progression was monitored. Kaplan-Meier's analysis was performed to measure overall survival. Protein levels of TRIM59 and p65 in xenograft tumor were determined by western blot. Direct binding of p65 on the TRIM59 promoter was analyzed by chromatin immunoprecipitation assay, and the regulatory effect was interrogated with luciferase reporter assay. Both TRIM59 and p65 were up-regulated in NSCLC. Eugenol treatment significantly inhibited xenograft tumor progression and prolonged the overall survival of tumor-bearing mice. Mechanistically, eugenol suppressed p65 expression, which subsequently decreased TRIM59 expression. TRIM59 deficiency fully recapitulated the anti-tumoral phenotype elicited by eugenol. Ectopic expression of TRIM59 completely abolished the tumor suppressive effect of eugenol, which underlined the predominant role of TRIM59 in mediating the signaling downstream of eugenol treatment. Eugenol inhibited NSCLC via repression NF-κB-TRIM59 pathway.

TRIM59 promotes gefitinib resistance in EGFR mutant lung adenocarcinoma cells.

AIMS: The relationship between TRIM59 and drug resistance is elusive despite of its multiple uncovered roles in human cancers. Here we aimed to characterize the expression status of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells and elucidate its mechanism underlying the drug resistance. MAIN METHODS: Gefitinib-resistant cell lines were established by progressive dosage. Relative expression of TRIM59 was determined by both real-time PCR and Western blot. Target gene knockdown was achieved by specific shRNAs. Cell viability was measured by MTT assay. Cell apoptosis was analyzed by flow cytometry with Annexin V/7-AAD double staining. Cell proliferation was determined by clonogenic formation assay. Migration and invasion capacities were detected using transwell chamber assay. Direct interaction between TRIM59 and STAT3 was analyzed by co-immunoprecipitation assay. KEY FINDINGS: We first observed overexpression of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells. ShRNA-mediated knockdown of TRIM59 significantly inhibited cell viability and stimulated apoptosis. Meanwhile, TRIM59-deficiency suppressed cell migration and invasion. We further identified the interaction between TRIM59 and STAT3. TRIM59-deficiency remarkably impaired the activation of STAT3 signaling. STAT3-specific shRNAs significantly re-sensitized TRIM59-proficient EGFR mutant lung adenocarcinoma cells to gefitinib. SIGNIFICANCE: Our data characterized aberrant TRIM59 overexpression in gefitinib-resistance EGFR mutant lung adenocarcinoma cells, and indicated the potential involvement of TRIM59-STAT3 signaling in the occurrence of gefitinib-resistance.

Non-enzymatic electrochemical hydrogen peroxide biosensor based on reduction graphene oxide-persimmon tannin­platinum nanocomposite.

Hydrogen peroxide (H2O2) is one of the most universal and essential ingredients in distinct biological tissues. Herein, a novel non-enzymatic sensor based on reduction graphene oxide-persimmon tannin­platinum nanocomposite (RGO-PT-Pt) was exploited for H2O2 detection. RGO-PT-Pt nanocomposite was prepared by reduction procedure with ascorbic acid as reducing agent and characterized by Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-vis) and Fourier infrared spectroscopy (FT-IR). Taking advantage of high electro-catalytic efficiency of Pt nanoparticles, high electronic conductivity and large surface area of RGO, and significant adsorption ability of PT on metal ions and its prevention of agglomeration to promote RGO dispersion, RGO-PT-Pt nanocomposite revealed better catalytic ability towards H2O2 via a synergistic effect. Under the optimal conditions, the RGO-PT-Pt non-enzymatic biosensor exhibited outstanding electrocatalytic activity towards H2O2 reduction. The amperometric response demonstrated a linear relationship with H2O2 concentration from 1.0 to100 µM with the correlation coefficient of 0.9931. The limit of detection was 0.26 µM (S/N = 3) and the response time was 3 s. Furthermore, the fabricated sensor exhibited a practical applicability in the quantification of H2O2 in human serum samples with an excellent recovery rate. Due to excellent performance such as fast response time, low detection limit, high stability and selectivity, the RGO-PT-Pt non-enzymatic biosensor has potential application in clinical diagnostics.

Label-free electrochemical aptasensor for detection of alpha-fetoprotein based on AFP-aptamer and thionin/reduced graphene oxide/gold nanoparticles.

Sensitive and accurate detection of tumor markers is critical to early diagnosis, point-of-care and portable medical supervision. Alpha fetoprotein (AFP) is an important clinical tumor marker for hepatocellular carcinoma (HCC), and the concentration of AFP in human serum is related to the stage of HCC. In this paper, a label-free electrochemical aptasensor for AFP detection was fabricated using AFP-aptamer as the recognition molecule and thionin/reduced graphene oxide/gold nanoparticles (TH/RGO/Au NPs) as the sensor platform. With high electrocatalytic property and large specific surface area, RGO and Au NPs were employed on the screen-printed carbon electrode to load TH molecules. The TH not only acted as a bridging molecule to effectively capture and immobilize AFP-aptamer, but as the electron transfer mediator to provide the electrochemical signal. The AFP detection was based on the monitoring of the electrochemical current response change of TH by the differential pulse voltammetry. Under optimal conditions, the electrochemical responses were proportional to the AFP concentration in the range of 0.1-100.0 µg/mL. The limit of detection was 0.050 µg/mL at a signal-to-noise ratio of 3. The proposed method may provide a promising application of aptamer with the properties of facile procedure, low cost, high selectivity in clinic.