m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism.

Glycolytic reprogramming is one of the most important features of cancer and plays an integral role in the progression of cancer. In cancer cells, changes in glucose metabolism meet the needs of self-proliferation, angiogenesis and lymphangiogenesis, metastasis, and also affect the immune escape, prognosis evaluation and therapeutic effect of cancer. The n6-methyladenosine (m6A) modification of RNA is widespread in eukaryotic cells. Dynamic and reversible m6A modifications are widely involved in the regulation of cancer stem cell renewal and differentiation, tumor therapy resistance, tumor microenvironment, tumor immune escape, and tumor metabolism. Lately, more and more evidences show that m6A modification can affect the glycolysis process of tumors in a variety of ways to regulate the biological behavior of tumors. In this review, we discussed the role of glycolysis in tumor genesis and development, and elaborated in detail the profound impact of m6A modification on different tumor by regulating glycolysis. We believe that m6A modified glycolysis has great significance and potential for tumor treatment.

A Novel Indole Derivative with Superior Photophysical Performance for Fluorescent Probe, pH-Sensing, and Logic Gates.

An indole-related molecules have been considered as the potential fluorescent probes for biological and electrochemical sensing. However, most of the indole probes have been usually used in a single detection mode. Indolium probes that enable accurate detection in complex environments are rarely reported. Here, four novel indole derivatives including the phenyl group substituted with different functional moieties were designed on the basis of the donor-π-acceptor (D-π-A) concept. These derivatives exhibit positive solvatochromism owing to their varied molecular conformations upon contacting to various solvents and the different HOMO-LUMO gaps caused by the difference in electronic push-pull capability of the substituents. Their solid-state fluorescence emissions and multiple chromisms are observed due to the inherent twisted geometries and aggregation modes. In addition, these derivatives show dramatic color and fluorescence responses due to the protonation of the nitrogen and oxygen containing groups, and thus novel colorimetric pH sensors, fluorescent papers and logic gates have been designed.

Three-Dimensional Metamaterial for Plasmon-Enhanced Raman Scattering at any Excitation Wavelengths from the Visible to Near-Infrared Range.

Plasmonic materials with highly confined electromagnetic fields at resonance wavelengths have been widely used to enhance Raman scattering signals. To achieve the maximum enhancement, the resonance peaks of the plasmonic materials should overlap with the excitation and emission wavelengths of target molecules, which is difficult for most of the plasmonic materials possessing a few narrow resonance peaks. Here, we report an ultrabroadband plasmonic metamaterial absorber (BPMA) that can absorb 99% of the incident light energy and excite plasmon resonance from the ultraviolet to near-infrared range (250-1900 nm), which allows us to observe efficient plasmon-enhanced Raman scattering (PERS) with any excitation sources. As demonstrated by the investigation on a self-assembled monolayer of the nonresonant molecule 4-mercaptobenzonitrile, the BPMA exhibits high PERS performance with a detection limit of down to 10-12 M under any excitation sources of three different lasers and excellent uniformity (∼5.51%) and reproducibility (∼5.50%), which corroborates the potential for high-throughput production with low cost and at a large scale. This work offers a novel platform for anti-interference PERS analysis in dynamic and complex environments.

Probing Multidimensional Structural Information of Single Molecules Transporting through a Sub-10 nm Conical Plasmonic Nanopore by SERS.

Probing the orientation and oxygenation state of single molecules (SMs) is of great importance for understanding the advanced structure of individual molecules. Here, we manipulate molecules transporting through the hot spot of a sub-10 nm conical gold nanopore and acquire the multidimensional structural information of the SMs by surface enhanced Raman scattering (SERS) detection. The sub-10 nm size and conical shape of the plasmonic nanopore guarantee its high detection sensitivity. SERS spectra show a high correlation with the orientations of small-sized single rhodamine 6G (R6G) during transport. Meanwhile, SERS spectra of a single hemoglobin (Hb) reveal both the vertical/parallel orientations of the porphyrin ring and oxygenated/deoxygenated states of Hb. The present study provides a new strategy for bridging the primary sequence and the advanced structure of SMs.

Prediction of Prognosis for cHCC-CC Patients After Surgery: Comparison of Tumor Marker Score Based on AFP, CEA, CA19-9, and Other Clinical Stages.

BACKGROUND: The effectiveness of clinical stage as a prognostic factor in combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) patients is controversial. PATIENTS AND METHODS: Medical records of all pathologically confirmed cHCC-CC patients from 2000 to 2017 at West China Hospital were retrieved. Tumor marker score (TMS) was determined from optimal AFP, CEA, and CA19-9 cutoff values. Interaction and subgroup analysis were conducted according to potential confounders. Prognostic value of TMS and other prognostic models were evaluated by Kaplan-Meier (K-M) analysis, c-index, and time-dependent receiver operating curves (td-ROC). RESULTS: Optimal cutoff values for preoperative AFP, CEA, and CA19-9 were 10.76 ng/mL, 5.24 ng/mL, and 31.54 U/mL, respectively. Among 128 patients, 24, 58, and 46 were classified into TMS 0, TMS 1, and TMS ≥ 2, respectively. TMS could stratify our series into groups of statistically different prognosis. Subgroup analysis according to potential confounders and test for interactions showed that TMS 1 and TMS ≥ 2 were stable risk factors relative to TMS 0. Univariate (HR: TMS1 = 2.30, p = 0.014; TMS ≥ 2 = 5.1, p < 0.001) and multivariate Cox regression analyses (HR: TMS1 = 1.72, p = 0.124; TMS ≥ 2 = 4.15, p < 0.001) identified TMS as an independent prognostic risk factor. TMS had good discrimination (c-index 0.666, 95% CI 0.619-0.714), and calibration plots revealed favorable consistency. Area under the curve (AUC) value of td-ROC for TMS and integrated AUC was higher than for other clinical stages at any month within 5 years postoperation. CONCLUSION: TMS exhibited optimal prognostic value over other widely used clinical stages for cHCC-CC after surgery and may guide clinicians in prognostic prediction.

Surface-Enhanced Raman Scattering Probing the Translocation of DNA and Amino Acid through Plasmonic Nanopores.

DNA and amino acids are important biomolecules in living organisms. Probing such biomolecules with structural characters can provide valuable information for life study. Here, gold plasmonic nanopores (GPNs) with high SERS activity (a local enhancement factor higher than 109) are synthesized at the tip of a glass nanopipette. An electric field drives individual molecules to translocate through the GPNs, which enables in situ collection of the surface-enhanced Raman scattering (SERS). Nonresonant biomolecules, including nucleobases, amino acids, and oligonucleotides (DNA), with single nucleobase differences can be distinguished. The intensity of SERS is tunable by modulating the affinity between DNA and the GPNs. The present study shows the feasibility of applying a plasmonic nanopore to DNA and protein detection, which may also provide an easy way for tracking single molecule translocation by developing a well-defined single plasmonic nanopore.

Structural Change of a Single Ag Nanoparticle Observed by Dark-field Microspectroscopy.

Silver nanoparticles (AgNPs) have been widely used as photocatalysts and nanosensors. Observation of the spectroscopy of a single AgNP greatly helps us understand the catalytic characteristics and morphology change of the AgNP during reactions. In the present study, AgNPs physically adsorbed on indium tin oxide (ITO) conductive glass were electrochemically reduced and oxidized, and the plasmonic resonance Rayleigh scattering (PRRS) spectrum of an individual AgNP was observed under a dark-field microscopy (DFM) equipped with a spectrometer. The electrochemical oxidization of the AgNP under constant potential caused a redshift of the PRRS peak for 30±5 nm. However, electrochemical reduction of the AgNP could not make the PRRS peak completely shift back to the initial position. In situ AFM and SEM characterization confirmed that very small Ag fragments (<10 nm) formed around the AgNP core during electrochemical oxidization. Results showed that dark-field microspectroscopy could be used as a sensitive tool for estimating the morphology/structural changes of nanoparticles that can hardly be observed through the cyclic voltammograms of multiple AgNPs.

Copper-Nitrogen-Doped Graphene Hybrid as an Electrochemical Sensing Platform for Distinguishing DNA Bases.

An electrochemical sensor using ultralight and porous copper-nitrogen-doped graphene (CuNRGO) nanocomposite as the electrocatalyst has been constructed to simultaneously determine DNA bases such as guanine (G) and cytosine (C), adenine (A), and thymine (T). The nanocomposite is synthesized by thermally annealing an ice-templated structure of graphene oxide (GO) and Cu(phen)2. Because of the unique structure and the presence of Cu2+-N active sites, the CuNRGO exhibits outstanding electrocatalytic activity toward the oxidation of free DNA bases. After optimizing the experimental conditions, the CuNRGO-based electrochemical sensor shows good linear responses for the G, A, T, and C bases in the concentration ranges of 0.132-6.62 µM, 0.37-5.18 µM, 198.2-5551 µM, and 270.0-1575 µM, respectively. The results demonstrate that CuNRGO is a promising electrocatalyst for electrochemical sensing devices.

Size-Controllable Gold Nanopores with High SERS Activity.

Nanopore structures have been successfully employed in next-generation DNA sequencing. For more complicated protein which normally contains 20 different amino acids, identifying the fluctuation of ionic current caused by different amino acids appears inadequate for protein sequencing. Therefore, it is highly desirable to develop size-controllable nanopores with optical activity that can provide additional structural information. Herein, we discovered the novel nanopore properties of the self-assembled ultramicroelectrodes originally developed by Bard and co-workers. Using a slightly modified method, the self-assembly of 7 ± 1 nm gold nanoparticles (AuNPs) can be precisely controlled to form a gold nanoporous sphere (GPS) on the tip of a glass capillary. Different dithiol linker molecules (1,3-propanedithiol, C3; 1,6-hexanedithiol, C6; and 1,9-nonanedithiol, C9) reproducibly led to rather similar nanopore sizes (5.07 ± 0.02, 5.13 ± 0.02, and 5.25 ± 0.01 nm), respectively. The GPS nanostructures were found to exhibit high ionic current rectification as well as surface-enhanced Raman scattering (SERS) activity due to the presence of nanopores and numerous "hot spots" among the cross-linked AuNPs on the surface of GPS. The rectification effect of the small nanopores was observed even under high concentration of electrolyte (290 mM), along with SERS enhancement factors well above 1 × 105. The GPS nanostructures were successfully applied for SERS-based detection of glutathione from a single HeLa cell.

Insight into the Unique Fluorescence Quenching Property of Metal-Organic Frameworks upon DNA Binding.

Metal-organic frameworks (MOFs) have been successfully used as efficient quenchers for fluorescent DNA detection. However, the surface charge property of MOFs can inevitably affect their fluorescence quenching behavior. Herein, nanoscale MOFs (NMOFs), including MOF nanosheets and nanoparticles, have been employed to investigate the relationship between the fluorescence quenching and surface properties of NMOFs. We find that the positively and negatively charged NMOFs exhibited totally opposite fluorescence quenching properties toward negatively charged FAM-labeled double-stranded DNA (dsDNA). On the contrast, they show negligible influence on the sensing of positively charged TAMRA-labeled dsDNA. This study provides a new insight of the fluorescence quenching property of NMOFs and offers a new concept for construction of ratiometric fluorescence DNA biosensors.

Nanopipette-Based SERS Aptasensor for Subcellular Localization of Cancer Biomarker in Single Cells.

Single cell analysis is essential for understanding the heterogeneity, behaviors of cells, and diversity of target analyte in different subcellular regions. Nucleolin (NCL) is a multifunctional protein that is markedly overexpressed in most of the cancer cells. The variant expression levels of NCL in subcellular regions have a marked influence on cancer proliferation and treatments. However, the specificity of available methods to identify the cancer biomarkers is limited because of the high level of subcellular matrix effect. Herein, we proposed a novel technique to increase both the molecular and spectral specificity of cancer diagnosis by using aptamers affinity based portable nanopipette with distinctive surface-enhanced Raman scattering (SERS) activities. The aptamers-functionalized gold-coated nanopipette was used to capture target, while p-mercaptobenzonitrile (MBN) and complementary DNA modified Ag nanoparticles (AgNPs) worked as Raman reporter to produce SERS signal. The SERS signal of Raman nanotag was lost upon NCL capturing via modified DNA aptamers on nanoprobe, which further helped to verify the specificity of nanoprobe. For proof of concept, NCL protein was specifically extracted from different cell lines by aptamers modified SERS active nanoprobe. The nanoprobes manifested specifically good affinity for NCL with a dissociation constant Kd of 36 nM and provided a 1000-fold higher specificity against other competing proteins. Furthermore, the Raman reporter moiety has a vibrational frequency in the spectroscopically silent region (1800-2300 cm-1) with a negligible matrix effect from cell analysis. The subcellular localization and spatial distribution of NCL were successfully achieved in various types of cells, including MCF-7A, HeLa, and MCF-10A cells. This type of probing technique for single cell analysis could lead to the development of a new perspective in cancer diagnosis and treatment at the cellular level.

Global concentration additivity and prediction of mixture toxicities, taking nitrobenzene derivatives as an example.

The toxicity of a mixture depends not only on the mixture concentration level but also on the mixture ratio. For a multiple-component mixture (MCM) system with a definite chemical composition, the mixture toxicity can be predicted only if the global concentration additivity (GCA) is validated. The so-called GCA means that the toxicity of any mixture in the MCM system is the concentration additive, regardless of what its mixture ratio and concentration level. However, many mixture toxicity reports have usually employed one mixture ratio (such as the EC50 ratio), the equivalent effect concentration ratio (EECR) design, to specify several mixtures. EECR mixtures cannot simulate the concentration diversity and mixture ratio diversity of mixtures in the real environment, and it is impossible to validate the GCA. Therefore, in this paper, the uniform design ray (UD-Ray) was used to select nine mixture ratios (rays) in the mixture system of five nitrobenzene derivatives (NBDs). The representative UD-Ray mixtures can effectively and rationally describe the diversity in the NBD mixture system. The toxicities of the mixtures to Vibrio qinghaiensis sp.-Q67 were determined by the microplate toxicity analysis (MTA). For each UD-Ray mixture, the concentration addition (CA) model was used to validate whether the mixture toxicity is additive. All of the UD-Ray mixtures of five NBDs are global concentration additive. Afterwards, the CA is employed to predict the toxicities of the external mixtures from three EECR mixture rays with the NOEC, EC30, and EC70 ratios. The predictive toxicities are in good agreement with the experimental toxicities, which testifies to the predictability of the mixture toxicity of the NBDs.

Insight into Ion Transfer through the Sub-Nanometer Channels in Zeolitic Imidazolate Frameworks.

A crack-free sub-nanometer composite structure for the study of ion transfer was constructed by in situ growth of ZIF-90 [Zn(ICA)2 , ICA=Imidazole-2-carboxaldehyde] on the tip of a glass nanopipette. The potential-driven ion transfer through the sub-nanometer channels in ZIF-90 is strongly influenced by the pH of the solution. A rectification ratio over 500 is observed in 1 m KCl solution under alkaline conditions (pH 11.58), which is the highest value reported under such a high salt concentration. Fluorescence experiments show the super-high rectification ratio under alkaline conditions results from the strong electrostatic interaction between ions and the sub-nanometer channels of ZIF-90. In addition to providing a general pathway for further study of mass-transfer process through sub-nanometer channels, the approach enable all kinds of metal-organic frameworks (MOFs) to be used as ionic permselectivity materials in nanopore-based analysis.

BML-111 Protected LPS/D-GalN-Induced Acute Liver Injury in Rats.

Lipoxins (LXs) display unique pro-resolving and anti-inflammatory functions in a variety of inflammatory conditions. The present study was undertaken to investigate the effects of BML-111 (5(S),6(R),7-trihydroxyheptanoic acid methyl ester), the agonist of lipoxin A4 receptor, in a model of Lipopolysaccharides (LPS) and d-Galactosamine (d-GalN) induced acute liver injury, and to explore the mechanisms. Histopathological analyses were carried out to quantify liver injury degree. The activities of myeloperoxidase (MPO) were examined to evaluate the levels of neutrophil infiltration. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were detected to evaluate the functions of the liver. The amounts of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1ß (IL-1ß) were measured using enzyme-linked immunosorbent assay (ELISA), and the expression levels of transforming growth factor-ß1(TGF-ß1) and cyclooxygenase-2 (COX-2) were examined using Western blotting. The antioxidant capacity, the activities of inducible nitric oxide synthase (iNOS), the contents of malondialdehyde (MDA) and nitric oxide (NO) were analyzed with the kits via biochemical analysis. We established the model of acute liver injury with lipopolysaccharide and d-Galactosamine (LPS/d-GalN): (1) histopathological results and MPO activities, with the activities of AST and ALT in serum, consistently demonstrated LPS and d-GalN challenge could cause severe liver damage, but BML-111 could prevent pathological changes, inhibit neutrophil infiltration, and improve the hepatic function; (2) LPS/d-GalN increased TNF-α, IL-1ß, COX-2, and IL-10, while decreasing TGF-ß1. However, BML-111 could repress LPS/d-GalN -induced TNF-α, IL-1ß and COX-2, meanwhile increasing the expression levels of TGF-ß1 and IL-10; (3) LPS/d-GalN inhibited the activities of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and hydroxyl radical-scavenging ability, simultaneously increasing the levels of MDA and NO, so also the activity of iNOS. Otherwise, BML-111 could reverse all the phenomena. In a word, BML-111 played a protective role in acute liver injury induced by LPS and d-GalN in rats, through improving antioxidant capacity and regulating the balance of inflammatory cytokines.

Zinc finger protein 180 induces an apoptotic phenotype by activating METTL14 transcriptional activity in colorectal cancer.

Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitation­PCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6­adenosine­methyltransferase non­catalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.

Performance of magnetic resonance elastography and diffusion-weighted imaging for the staging of hepatic fibrosis: A meta-analysis.

UNLABELLED: A meta-analysis was performed to assess and compare the accuracies of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for the staging of hepatic fibrosis. Online journal databases and a manual search from January 2000 to May 2011 were used. We identified 41 studies, but only 14 met the criteria to perform a meta-analysis assessing MRE (five trials) or DWI (10 trials). Fibrosis was categorized by redistribution into five stages according to histopathological description. A bivariate binomial model was used to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from which diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (sROC) were derived to indicate the diagnostic accuracy of imaging modalities. With MRE, the sensitivity, specificity, DOR, PLR, NLR, and area under sROC curve (with 95% CIs) for staging F0 ∼ F1 versus F2 ∼ F4 and F0 ∼ F2 versus F3 ∼ F4 were 0.94 (0.81-0.98), 0.95 (0.87-0.98), 20 (7-57), 0.06 (0.02-0.22), 317 (55-1,796), 0.98 (0.97-0.99) and 0.92 (0.85-0.96), 0.96 (0.91-0.98), 21 (10-45), 0.08 (0.04-0.16), 251 (103-609), and 0.98 (0.96-0.99), respectively; and with DWI, these values were 0.77 (0.71-0.82), 0.78 (0.69-0.85), 3 (2-5), 0.30 (0.22-0.40), 12 (6-21), 0.83 (0.79-0.86) and 0.72 (0.60-0.81), 0.84 (0.77-0.89), 5 (3-7), 0.34 (0.23-0.50), 13 (6-29), and 0.86 (0.83-0.89), respectively. A z test demonstrated that MRE had a significantly higher accuracy than DWI in those indicators (P < 0.05). CONCLUSION: MRE is more reliable for staging hepatic fibrosis, compared with DWI, with a high combination of sensitivity, specificity, likelihood ratios, DOR, and area under sROC curve.

Modeling non-monotonic dose-response relationships: model evaluation and hormetic quantities exploration.

Non-monotonic (biphasic) dose-response relationships, known as hormetic relationships, have been observed across multiple experimental systems. Several models were proposed to describe non-monotonic relationships. However, few studies provided comprehensive description of hermetic quantities and their potential application. In this study, five biphasic models were used to fit five hormetic datasets from three different experimental systems of our lab. The bisection algorithm based on individual monotone functions was proposed to calculate arbitrary hormetic quantities instead of traditional methods (e.g., model reparameterization) which need complex mathematical manipulation. Results showed that all the five biphasic models could describe those datasets fairly well with coefficient of determination ( R(2) adj) greater than 0.95 and root mean square error (RMSE) smaller than 0.10. The best-fit model could be selected based on EC(R10), RMSE, and a supplemental criterion of Akaike information criterion (AIC). Hormetic quantities that trigger 10% stimulation at the left (EC(L10)) and right (EC(R10)) side of stimulatory peak were calculated and emphasized for their implication in hormesis exploration for the first time. Furthermore, the EC(L10), proposed as an alarm threshold for hormesis, was expected to be useful in risk assessment of environmental chemicals. This study lays a foundation in the quantitative description of the low dose hormetic effect and the investigation of hormesis in environmental risk assessment.

[Simplification of NIR model for citrus's sugar content based on sensory methods].

The prediction of sugar content (SC) in citrus by near-infrared spectroscopy (NIRS) and sensory test was investigated the validation whether the result of non-destructive determination methods by NIRS can meet the request of consumers' sensory or not, and the simplification of the prediction model of NIRS for citrus's SC with variables selection on the basis of meeting their demands. Result of the latter analyzed by one-way ANOVA shows that there was a significant difference influenced by individual diversity, but not by gender. After excluding the sensuous outliers, root mean standard error of deviation (RMSED) of every participator was calculated and the minimum equaled to 0.633, which was chosen as borderline of NIR model's RMSEP to meet the sensory request Then, combined with spectral preprocessing and variables selection methods, SPA-MLR model was obtained by its robustness with Rp = 0.86, as well as RMSEP = 0.567 for prediction set, furthermore, prediction time just costs 6.8 ms. The achievement that not only meets the customers' sensory, but also simplifies the prediction model can be a good reference for real time application in future.

Gold Nanotriangle-Assembled Nanoporous Structures for Electric Field-Assisted Surface-Enhanced Raman Scattering Detection of Adenosine Triphosphate.

A reliable, rapid, cost-effective, and simple method for the detection of biomolecules would greatly promote the research of analytical detection of single molecules. A nanopore-based analytical technique is promising for detecting biomolecules. Conventional electrochemical nanopores cannot distinguish biomolecules precisely because of their fast translocation speed and limited electrochemical information. Therefore, it is highly desirable to develop electrochemical surface-enhanced Raman scattering (SERS) nanopores to obtain multidimensional information. Herein, we designed and fabricated gold nanotriangle (AuNT)-assembled porous structures at the tip of a glass capillary using dithiol adenosine triphosphate (ATP) aptamers as cross-linking molecules. The AuNTs exhibited an edge length of 57.3 ± 6.2 nm and thickness of about 15 nm. The gold nanoporous structure (GPS) showed a strong ion rectification even at a high concentration of electrolyte (2 M) and a high SERS activity. Based on these designed structures, SERS and electrochemistry techniques were combined to control the rapid movement of ATP to the vicinity of the GPS by an applied potential of +1 V, where ATP was concentrated by ATP aptamers and the molecular signals were amplified by SERS. As a result, the GPS successfully detected ATP at a concentration as low as 10-7 M.

Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed. METHODS: We performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. RESULTS: A total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL. CONCLUSIONS: Our study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL.