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Purpose The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms. Methods Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red. Results It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells. Conclusion It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

Background: CT screening can detect lung cancer early but suffers a high false-positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan. Methods: We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific antimicrobial antibodies. Results: Analyzing fourth quartile ORs, we found more antibodies with higher prevalence in the three BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-Helicobacter pylori antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤20 pack-years) compared with heavy smokers (>20 pack-years), in BNC with nodule size >1 cm than in those with ≤1 cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC versus SMC and ADC versus BNC with area under the ROC curve (AUC) of 0.88 and 0.80, respectively. Conclusions: Antimicrobial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development. Impact: Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.

Supplementary Figure S4 from Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules

Supplementary Table S2 from Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules

Background:CT screening can detect lung cancer early but suffers a high false-positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan.Methods:We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific antimicrobial antibodies.Results:Analyzing fourth quartile ORs, we found more antibodies with higher prevalence in the three BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-Helicobacter pylori antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤20 pack-years) compared with heavy smokers (>20 pack-years), in BNC with nodule size >1 cm than in those with ≤1 cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC versus SMC and ADC versus BNC with area under the ROC curve (AUC) of 0.88 and 0.80, respectively.Conclusions:Antimicrobial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development.Impact:Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.

Introducing polymerizable monomers into a binary hexagonal lyotropic liquid crystalline (LLC) template is a straightforward way for retaining the nanostructure but will decrease attractive intra- and inter- aggregate interactions. It is therefore crucial to understand the interfacial interactions at nanoscale after introducing the monomers but prior to polymerization. Herein, active species, poly (ethylene glycol) diacrylate (PEGDA) and 2-hydroxyethyl methacrylate (HEMA), were introduced into hexagonal LLC of dodecyl trimethylammonium bromide and water to explore the structural variables, dimensional stability, and dynamic property. At a proper volume ratio of PEGDA/HEMA (1/4), the system presents excellent homogeneity with a higher dimensional stability and lower dynamic property from rheological assessments, thereby achieving robust, free-standing, and transparent membranes after photo-polymerization. The unique property of the system also lies in the much lower order–disorder transition temperature (45 °C) that facilitates the reorientation of mesochannels. They are in contrast inaccessible for the ternary system only with PEGDA, though the nanostructure for both systems could be retained. An insight into subtle variations in these parameters allows us to prepare a polymerizable template possessing higher dimensional stability and suitable flexibility via molecular design, thereby enabling simultaneous structural alignment and retention for the development of functional nanomaterials.

A nanoscale Li-ion battery was constructed with a single MnO@C nanorod and the lithiation process during electrochemical reaction were in situ visualized in an aberration-corrected environmental transmission electron microscope.

The rapid development of the intelligent equipment industry has promoted the emergence of a series of emerging industries, effectively improving the technical level of society and people’s quality of life. Due to the inherent characteristics of smart devices, smart devices face serious privacy disclosure risks. Therefore, we have studied the security problem of the widely used smart device smart bracelet in this paper. We have adopted the attack method from easy to difficult to obtain the reading and writing instructions and timing characteristics of the intelligent devices to attack and steal private information. Specifically, we first attack through the strategy of log analysis; if this method is unable to obtain effective information, then we further acquire sensitive information on the basis of hook technology; and if the method on the basis of hook technology is still unable to obtain relevant information, then we will further use reverse engineering to conduct reverse analysis on the app to obtain sensitive information. Second, we develop a fake app on the basis of sensitive information and use it as a bridge to attack intelligent devices. In order to verify the effectiveness of the method, we successfully attacked and stole information from three popular business intelligence bracelets of different brands on the basis of the proposed method. The first step is to develop a fake app on the basis of the identified vulnerabilities. This app can bypass the protection measures of confusion and forced pairing and resetting to cheat the smart bracelet and can successfully enable or disable the jitters function remotely to modify the time and to obtain the sensitive data of the smart bracelet owner. In our attack process, we do not need the cooperation of the owner of the smart bracelet, nor do we need the target smart bracelet to match with our app.

Prorocentrum donghaiense blooms occur annually in the East China Sea coastal waters, degrading ecosystem functions and impeding economic development. Dissolved organic nitrogen and phosphorus (DON and DOP) are the main components in the marine nutrient pools and are closely related to harmful algal blooms. From April to June 2019, a survey was conducted along the East China Sea coast (Sansha and Lianjiang counties) to investigate the relationship between dissolved organic nutrients and P. donghaiense bloom. Our findings showed that dinoflagellates dominated the phytoplankton community, and dissolved organic nutrients were the major factors influencing community structure during the P. donghaiense bloom. Redundancy analysis indicated that P. donghaiense abundance was primarily affected by DON in the Sansha area while it was primarily affected by DON and DOP in the Lianjiang area. Correlation analysis also confirmed a strong positive correlation between dissolved organic nutrients and P. donghaiense abundance both in the Sansha and Lianjiang coastal areas (p 0.001). Furthermore, a culture experiment was carried out during the bloom to further investigate the effect of dissolved organic nutrients on the phytoplankton community structure. After 10 days of culture, dinoflagellates' relative abundance decreased from 97.1% to 28.2% in the inorganic treatment, whereas dinoflagellates continued to dominate the phytoplankton community in the organic treatment (76.9%). As a result, we propose that dissolved organic nutrients are responsible for the P. donghaiense bloom outbreak and promote the phytoplankton community shift from diatoms to dinoflagellates.

Discovering novel changes in the proteome of malignant lung epithelial cells and/or the tumor-microenvironment is paramount for diagnostic, prognostic, and/or therapy development. A time-dependent 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mouse lung tumor model was used to screen the proteome of lung tumors. NNK-transformed human lung epithelial BEAS-2B cells were then established to evaluate the epithelial cell-specific protein changes. A duration-dependent increase of tumor burden was observed in NNK-treated mice, 2/12 (17%), 8/12 (67%), 9/12 (75%), and 10/10 (100%) at weeks 8, 12, 16, and 20 after the NNK exposure, respectively. A total of 25 differentially expressed proteins (≥ twofold change), predominantly structural, signaling, and metabolic proteins, were detected by two-dimensional difference gel electrophoresis and identified by mass spectrometry. Calregulin, ezrin, histamine releasing factor (HRF), and inorganic pyrophosphatase 1 (PPA1) exhibited changes and were further confirmed via immunoblotting. In addition, immunohistochemistry (IHC) analysis indicated upregulated E-cadherin and decreased vimentin expression in epithelial cells of tumor tissues. Acquisition of a neoplastic phenotype in NNK-transformed BEAS-2B cells was demonstrated by enhanced wound closure and increased anchorage independent colony formation. In transformed BEAS-2B cells, protein expression of E-cadherin, ezrin, and PPA1 (but not calregulin and HRF) was upregulated, as was observed in tumor tissues IHC staining using mouse lung tumor tissues further revealed that HRF upregulation was not lung epithelial cell specific. Altogether, tumorigenesis after NNK exposure may be initiated by protein dysregulation in lung epithelial cells together with proteome derangement derived from other cell types existing in the tumor-microenvironment.

Computer Tomography (CT) screening can detect lung cancer early but suffers a high false positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan.We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific anti-microbial antibodies.Analyzing 4th quartile odds ratios, we found more antibodies with higher prevalence in the 3 BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-Helicobacter pylori antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤ 20 pack-years) compared with heavy smokers (20 pack-years), in BNC with nodule size1cm than in those with= 1cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC vs. SMC and ADC vs. BNC with area under the receiver operating characteristics curve (AUC) of 0.88 and 0.80, respectively.Anti-microbial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development.Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.

BACKGROUND: Around 10% of gastric carcinomas (GC) contain Epstein-Barr virus (EBV) DNA. We characterized the GC-specific antibody response to this common infection, which may provide a noninvasive method to detect EBV-positive GC and elucidate its contribution to carcinogenesis. METHODS: Plasma samples from EBV-positive (n=28) and EBV-negative (n=34) Latvian GC patients were immune-profiled against 85 EBV proteins on a multi-microbial Nucleic Acid Programmable Protein Array (EBV-NAPPA). Antibody responses were normalized for each sample as ratios to the median signal intensity (MNI) across all antigens, with seropositivity defined as MNI ≥2. Antibodies with ≥20% sensitivity at 95% specificity for tumor EBV status were verified by enzyme-linked immunosorbent assay (ELISA) and validated in independent samples from Korea and Poland (n=24 EBV-positive, n=65 EBV-negative). RESULTS: Forty anti-EBV IgG and 8 IgA antibodies were detected by EBV-NAPPA in ≥10% of EBV-positive or EBV-negative GC patients, of which 9 IgG antibodies were discriminative for tumor EBV status. Eight of these nine were verified and seven were validated by ELISA: anti-LF2 (odds ratio=110.0), anti-BORF2 (54.2), anti-BALF2 (44.1), anti-BaRF1 (26.7), anti-BXLF1 (12.8), anti-BRLF1 (8.3), and anti-BLLF3 (5.4). The top three had areas under receiver operating characteristics curves of 0.81–0.85 for distinguishing tumor EBV status. CONCLUSIONS: The EBV-associated GC-specific humoral response was exclusively directed against lytic cycle immediate-early and early antigens, unlike other EBV-associated malignancies such as nasopharyngeal carcinoma and lymphoma where humoral response is primarily directed against late lytic antigens. Specific anti-EBV antibodies could have utility for clinical diagnosis, epidemiologic studies, and immune-based precision treatment of EBV-positive GC.

Acrylamide has been shown to be neurotoxic. Brain-derived neurotrophic factor (BDNF) can alleviate acrylamide-induced synaptic injury; however, the underlying mechanism remains unclear. In this study, dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma (NB-1) cells were exposed with 0-100 μg/mL acrylamide for 24-72 hours. Acrylamide decreased cell viability and destroyed synapses. Exposure of co-cultured NB-1 cells and Schwann cells to 0-100 μg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF, suggesting that Schwann cells can activate self-protection of neurons. Under co-culture conditions, activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect. Exogenous BDNF can increase expression of TrkB, Erk1/2, and synapsin I, while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes. Taken together, Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway, indicating that BDNF plays an important role in this process. Therefore, exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control, a division of the Chinese Center for Disease Control and Prevention (approval No. EAWE-2017-008) on May 29, 2017.

Chronic Helicobacter pylori infection is the major risk factor for gastric cancer (GC). However, only some infected individuals develop this neoplasia. Previous H. pylori serology studies have been limited by investigating small numbers of candidate antigens. Therefore, we evaluated humoral responses to a nearly complete H. pylori immunoproteome (1527 proteins) among 50 GC cases and 50 controls using Nucleic Acid Programmable Protein Array (NAPPA). Seropositivity was defined as median normalized intensity ≥2 on NAPPA, and 53 anti-H. pylori antibodies had >10% seroprevalence. Anti-GroEL exhibited the greatest seroprevalence (77% overall), which agreed well with ELISA using whole-cell lysates of H. pylori cells. After an initial screen by H. pylori-NAPPA, we discovered and verified that 12 antibodies by ELISA in controls had ≥15% of samples with an optical reading value exceeding the 95th percentile of the GC group. ELISA-verified antibodies were validated blindly in an independent set of 100 case-control pairs. As expected, anti-CagA seropositivity was positively associated with GC (odds ratio, OR = 5.5; p < 0.05). After validation, six anti-H. pylori antibodies showed lower seropositivity in GC, with ORs ranging from 0.44 to 0.12 (p < 0.05): anti-HP1118/Ggt, anti-HP0516/HsIU, anti-HP0243/NapA, anti-HP1293/RpoA, anti-HP0371/FabE, and anti-HP0875/KatA. Among all combinations, a model with anti-Ggt, anti-HslU, anti-NapA, and anti-CagA had an area under the curve of 0.73 for discriminating GC vs. controls. This study represents the first comprehensive assessment of anti-H. pylori humoral profiles in GC. Decreased responses to multiple proteins in GC may reflect mucosal damage and decreased bacterial burden. The higher prevalence of specific anti-H. pylori antibodies in controls may suggest immune protection against GC development.

A lithium metal anode is regarded as the most promising anode material for the next generation of high-energy density batteries because of its high specific capacity and low reduction potential. Ho...

Extensively used in several industries in China as a cleaning agent, 1-bromopropane (1-BP) has significant adverse effects on the central nervous system. However, neither its mechanism of action nor sensitive biomarkers related to it have been determined thus far. In this study, animal experiments and occupational surveys were performed to explore the typical exposure and effect biomarkers of neurotoxicity induced by 1-BP. Male Wistar rats were exposed to 0, 500, or 1000 ppm of 1-BP followed by pathological and biomarker analyses. An epidemiological survey was conducted on 71 workers each from 1-BP exposed and control groups. Serum and urine samples were collected for biomarker testing. cNSE represents neuron-specific enolase (NSE) in the cerebral cortex, where as sNSE represents NSE in the serum; similar terminology applies to S-100β, and cyclooxygenase-2 (COX-2). In rats exposed to 1000 ppm 1-BP, pathological changes were observed in Purkinje cells, lumbar gray matter, and tibiofibular nerve, while levels of cNSE, cS-100β, cCOX-2, sS-100β, and sCOX-2 were significantly elevated at different time checkpoints. In the 500 ppm group, cCOX-2, sNSE, and sCOX-2 levels were significantly elevated at different time checkpoints. 1-BP and N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) were detected in rat urine, and there was a correlation between the level of sNSE or sCOX-2 and AcPrCys in the 500 ppm group. In the occupational epidemiological study, a significant correlation between AcPrCys and exposure concentration was also detected. The findings of this study indicated that AcPrCys was a sensitive exposure biomarker of 1-BP in rats as well as occupational populations.