Preparation and Performance Evaluation of Ionic Liquid Copolymer Shale Inhibitor for Drilling Fluid Gel System.

An inhibitor that can effectively inhibit shale hydration is necessary for the safe and efficient development of shale gas. In this study, a novel ionic liquid copolymer shale inhibitor (PIL) was prepared by polymerizing the ionic liquid monomers 1-vinyl-3-aminopropylimidazolium bromide, acrylamide, and methacryloyloxyethyl trimethyl ammonium chloride. The chemical structure was characterized using fourier transform infrared spectroscopy (FT-IR) and hydrogen-nuclear magnetic resonance (H-NMR), and the inhibition performance was evaluated using the inhibition of slurrying test, bentonite flocculation test, linear expansion test, and rolling recovery test. The experimental results showed that bentonite had a linear expansion of 27.9% in 1 wt% PIL solution, 18% lower than that in the polyether amine inhibitor. The recovery rate of shale in 1 wt% PIL was 87.4%. The ionic liquid copolymer could work synergistically with the filtrate reducer, reducing filtration loss to 7.2 mL with the addition of 1%. Mechanism analysis showed that PIL adsorbed negatively charged clay particles through cationic groups, which reduced the electrostatic repulsion between particles. Thus, the stability of the bentonite gel systems was destroyed, and the hydration dispersion and expansion of bentonite were inhibited. PIL formed a hydrophobic film on the surface of clay and prevented water from entering into the interlayer of clay. In addition, PIL lowered the surface tension of water, which prevented the water from intruding into the rock under the action of capillary force. These are also the reasons for the superior suppression performance of PIL.

Exploring the Preferences of Parents of Children with Myopia in Rural China for Eye Care Services Under Privatization Policy: Evidence from a Discrete Choice Experiment.

OBJECTIVES: This study aims to measure the preferences and valuations of parents of students with myopia parents for eye care service attributes in rural China, and to quantify the potential welfare impacts of privatization policy on children's eye care services. METHODS: A discrete choice experiment was designed and implemented among a sample of parents of children with myopia in rural China. We randomly selected 350 participants from the list of subjects obtained from local town schools and family doctors using a random number table method. The participants were asked to choose between two hypothetical scenarios defined by five attributes: provider type, distance, price, lenses type, and refractionists' professional competencies. We estimate conditional logit and mixed logit models to approximate individual preferences for these attributes and estimate the welfare effects by calculating willingness to pay. RESULTS: Respondents (n = 336) showed a significant preference for public providers of refractive error services, myopia control lenses, and professional refractionists (P < 0.01 for each). Consumer welfare losses due to a prohibition of the public provision of refractive error services could be compensated by improving the quality of products and services delivered by private providers. Lastly, both parent and child demographics and previous experience of eye care service consumption are important predictors of willingness to pay for refractive error services. CONCLUSIONS: The privatization policy on children's eye care services would not cater to the preferences of rural consumers, inevitably leading to welfare losses. However, reduced consumer welfare could be compensated by improving the quality of products and service delivery from private providers. These results could help inform strategies to improve and reduce inequities in access to high-quality eye care services in rural China.

Prevalence of self-reported chronic conditions and poor health among older adults with and without vision impairment in China: a nationally representative cross-sectional survey.

OBJECTIVE: To examine the self-reported prevalence of 13 chronic conditions and poor health among Chinese adults aged 45 years and older with and without self-reported vision impairment. DESIGN: Cross-sectional study from the China Health and Retirement Longitudinal Study 2018, a nationally representative survey of Chinese adults aged 45 years and older involving 19 374 participants. METHODS: We used logistic regression to assess the association between vision impairment and 13 common chronic conditions and between vision impairment and poor health for those with any of these chronic conditions. RESULTS: Older people with self-reported vision impairment were significantly more likely to report all 13 chronic conditions (all p<0·05). After controlling for age, gender, education, residential status (rural vs urban), smoking and BMI, the highest adjusted odds were for hearing impairment (OR=4.00 (95% CI 3·60 to 4·44]) and depression (OR=2.28 (95% CI 2.06 to 2.51)). The lowest risk, though still significant, was for diabetes (OR=1·33 (95% CI 1.11 to 2.05)) and hypertension (OR=1.20 (95% CI 1.04 to 1.38)). After controlling for these potential confounding factors, among older people with chronic conditions, those with vision impairment were 2.20 to 4.04 times more likely to have poor health, compared with those without vision impairment (all p<0.001), with the exception of cancer (p=0.595). CONCLUSIONS: Higher prevalence of chronic conditions is strongly associated with vision impairment among older Chinese adults and poor health is strongly associated with vision impairment among people with chronic conditions.

EphA2 is a functional entry receptor for HCMV infection of glioblastoma cells.

Human cytomegalovirus (HCMV) infection is associated with human glioblastoma, the most common and aggressive primary brain tumor, but the underlying infection mechanism has not been fully demonstrated. Here, we show that EphA2 was upregulated in glioblastoma and correlated with the poor prognosis of the patients. EphA2 silencing inhibits, whereas overexpression promotes HCMV infection, establishing EphA2 as a crucial cell factor for HCMV infection of glioblastoma cells. Mechanistically, EphA2 binds to HCMV gH/gL complex to mediate membrane fusion. Importantly, the HCMV infection was inhibited by the treatment of inhibitor or antibody targeting EphA2 in glioblastoma cells. Furthermore, HCMV infection was also impaired in optimal glioblastoma organoids by EphA2 inhibitor. Taken together, we propose EphA2 as a crucial cell factor for HCMV infection in glioblastoma cells and a potential target for intervention.

Nano-laponite/polymer composite as filtration reducer on water-based drilling fluid and mechanism study.

In drilling deep complex formations, most drilling fluid additives have insufficient temperature and salt tolerance, resulting in the decline of drilling fluid performance. This study used 2-acrylamide-2-methylpropane sulfonic acid, acrylamide, dimethyl diallyl ammonium chloride and modified nano-laponite to synthesize a nanocomposite filtrate reducer (ANDP) with excellent temperature and salt resistance, which can maintain the performance of drilling fluid. The structure of ANDP was analysed by a transmission electron microscope and an infrared spectrometer. The thermal stability of ANDP was studied by thermogravimetric analysis. The performance of ANDP was evaluated in a water-based drilling fluid. The mechanism was analysed per clay particle size distribution, Zeta potential, filter cake permeability and scanning electron microscopy imaging. The results show that ANDP has good thermal stability and the expected molecular structure. The filtration of freshwater drilling fluid after ageing at 200°C is 10.4 ml and that of saturated brine drilling fluid is 6.4 ml after ageing at 150°C. Mechanism analysis suggests that the ANDP increases the thickness of clay particle hydration layer and maintains the colloidal stability of the drilling fluid. ANDP inhibits the agglomeration of clay particles and significantly reduces the filtration by forming dense mud cake.

Synthesis of a Low-Molecular-Weight Filtrate Reducer and Its Mechanism for Improving High Temperature Resistance of Water-Based Drilling Fluid Gel System.

During the exploitation of deep and ultradeep oil and gas resources, the high-temperature problem of deep reservoirs has become a major challenge for water-based drilling fluids. In this study, a novel high-temperature-resistant filtrate reducer (LDMS) with low molecular weight was synthesized using N, N-dimethylacrylamide; sodium p-styrene sulfonate; and maleic anhydride, which can maintain the performance of a drilling fluid gel system under high temperature. Unlike the conventional high-temperature-resistant polymer filtrate reducer, LDMS does not significantly increase the viscosity and yield point of the drilling fluid gel systems. After aging at 210 °C, the filtrate volume of a drilling fluid with 2 wt% LDMS was only 8.0 mL. The mechanism of LDMS was studied by particle size distribution of a drilling fluid gel system, Zeta potential change, adsorption experiment, change of bentonite interlayer spacing, filter cake scanning electron microscope, and related theoretical analysis. The mechanism study revealed that LDMS could be adsorbed on the surface of bentonite particles in large quantities and intercalated into the interlayer of bentonite. Thus, it can improve the hydration degree of bentonite particles and the colloidal stability of the drilling fluid gel system, maintain the content of fine particles in the drilling fluid gel system, form a compact mud cake, and significantly reduce the filtrate volume of the drilling fluid gel system. Therefore, this work will promote the application of a low-molecular-weight polymer filtrate reducer in high-temperature-resistant water-based drilling fluid gel systems.

Exergy Analysis of Phase-Change Heat-Storage Coupled Solar Heat Pump Heating System.

With the rapid development of industrialization, the excessive use of fossil fuels has caused problems such as increased greenhouse gas emissions and energy shortages. The development and use of renewable energy has attracted increased attention. In recent years, solar heat pump heating technology that uses clean solar energy combined with high-efficiency heat pump units is the development direction of clean heating in winter in northern regions. However, the use of solar energy is intermittent and unstable. The low-valley electricity policy is a night-time electricity price policy. Heat pump heating has problems such as frosting and low efficiencies in cold northern regions. To solve these problems, an exergy analysis model of each component of a phase-change heat-storage coupled solar heat pump heating system was established. Exergy analysis was performed on each component of the system to determine the direction of optimization and improvement of the phase-change heat-storage coupled solar heat pump heating system. The results showed that optimizing the heating-end heat exchanger of the system can reduce the exergy loss of the system. When the phase-change heat-storage tank meets the heating demand, its volume should be reduced to lower the exergy loss of the tank heat dissipation. Air-type solar collectors can increase the income exergies of solar collectors.

Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01 (a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma.

OBJECTIVE: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01 (a rituximab biosimilar) and reference rituximab sourced from China (MabThera®; rituximab-CN). METHODS: Here we report the results of two phase 1 studies. In the phase 1a, open-label, dose-escalation study (NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m2 HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity (DLT). In the phase 1b, double-blind study (NCT02584920, CTR20140764), eligible patients were given a single dose of 375 mg/m2 HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1a and the area under the plasma concentration-time curve from time zero to day 91 (AUC0-91 d) for the phase 1b study. Equivalence was concluded if 90% confidence interval (90% CI) for the geometric least squares mean ratio (GLSMR) fell in the pre-specified equivalence criteria (80%-125%). RESULTS: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events (AEs), discontinuations or DLTs. Between November 8, 2014 and August 13, 2015, 87 eligible patients were enrolled in the phase 1b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6% (90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups. CONCLUSIONS: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma. HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles.

Small-scale alpine topography at low latitudes and high altitudes: refuge areas of the genus Chrysanthemum and its allies.

Cultivated chrysanthemum (Chrysanthemum morifolium Ramat.) is an economically important ornamental plant species grown worldwide. However, the origin of the genus Chrysanthemum remains unclear. This study was conducted in the Hengduan Mountains, Yunnan Province. We took advantage of a special geographic region where the southernmost species of Ajania and the highest altitude population of Chrysanthemum indicum coexist to investigate their evolutionary origins. Diversity analysis of 9 populations of 5 species that came from 3 genera was carried out based on morphological traits and SRAP markers. Furthermore, topographical and ecological analyses and surveys of the vegetation communities in the plots were carried out for correlation analysis, and past data were used to reconstruct the ancient topography and vegetation to estimate the migration path and divergence time. We found that Chrysanthemum and Ajania were closely related based on the smooth transition states among marginal female florets and their common pollination system. The genetic relationship between Phaeostigma and Chrysanthemum was relatively distant, and Ajania was between them. Low light intensity and relatively humid habitats may be driving the elongation and evolution of marginal female florets. We found that Chrysanthemum and related genera were largely restricted to stony topographies at an altitude of ~3000 m.a.s.l. and in specialized alpine coniferous (Pinus) and broad-leaved (Quercus) mixed forest marginal communities. These stony topographies have become ecological islands of refuge for these species in the current interglacial period. The Hengduan Mountains play a key role in the evolution, divergence, and survival of Chrysanthemum and its allies.

The Synthesis of Polymeric Nanospheres and the Application as High-Temperature Nano-Plugging Agent in Water Based Drilling Fluid.

Nanoscale plugging agent is essential to wellbore stability of troublesome shale formation in the drilling of oil and gas wells. In this paper, polymeric nanospheres (PNS) with a double cross-linked structure were synthesized using monomers of styrene (ST), acrylamide (AM), 2-Acrylamide- 2-methylpropanesulfonic acid (AMPS), and dimethyl diallyl ammonium chloride (DMDAAC). PNS were characterized by FTIR, SEM and TGA. The plugging performance of PNS was analyzed using nitrogen adsorption experiments and SEM. And compatibility with water based drilling fluid (WBM) was studied. Experimental results showed that PNS had a mean particle size of 133 nm, and could retain about half of the original size after high temperature treatment under 150-200°C. TGA showed that the initial decomposition temperature of PNS is around 315°C. After plugging by PNS, both the specific surface area and pore volume of the shale cuttings decreased substantially compared with those of shale samples treated with water. Thus, PNS was thermal stable in WBM under high temperature and could effectively plug shale pores. Besides, PNS was beneficial to reduce both API and HTHP fluid loss of WBM.

Migration of titanium dioxide from PET/TiO2 composite film for polymer-laminated steel.

PET/TiO2 composite film is the most widely used film for polymer-laminated steel, and the migration of TiO2 is very important for the safety evaluation of its packaged food. Microwave digestion, wet digestion and dry ashing were used for pretreatment of composite film to determine the content of TiO2 in composite film. Migration tests were carried out at 40°C, 60°C and 80°C 4% using acetic acid and 50% ethanol as the acid and ester food simulants. The migration amount of TiO2 was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). With increasing temperature and time, the migration of TiO2 increased. In 4% acetic acid, the migration amount of TiO2 at 40°C for 10 days was 1.88 mg kg-1 and the migration amount at 80°C for 8 h was 3.32 mg kg-1, indicating that the effect of temperature on migration was more obvious. Under the same conditions, the migration amount of TiO2 in 4% acetic acid was greater than in 50% ethanol. X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC) were used to analyse the crystal structure, morphology, chemical groups and thermal properties of the film before and after the migration tests. The results showed that filmTiO2 had a stable rutile type crystal structure and it was almost uniformly distributed. PET and TiO2 were combined with strong chemical bonds. After TiO2 migration, the crystallinity and the glass transition temperature (Tg) of the film decreased, but the change of melting temperature (Tm) was not obvious.

EasyLB: Adaptive Load Balancing Based on Flowlet Switching for Wireless Sensor Networks.

Load balancing is effective in reducing network congestion and improving network throughput in wireless sensor networks (WSNs). Due to the fluctuation of wireless channels, traditional schemes achieving load balancing in WSNs need to maintain global or local congestion information, which turn out to be complicated to implement. In this paper, we design a flowlet switching based load balancing scheme, called EasyLB, by extending OpenFlow protocol. Flowlet switching is efficient to achieve adaptive load balancing in WSNs. Nevertheless, one tricky problem lies in determining the flowlet timeout value, δ . Setting it too small would risk reordering issue, while setting it too large would reduce flowlet opportunities. By formulating the timeout setting problem with a stationary distribution of Markov chain, we give a theoretical reference for setting an appropriate timeout value in flowlet switching based load balancing scheme. Moreover, non-equal probability path selection and multiple parallel load balancing paths are considered in timeout setting problem. Experimental results show that, by setting timeout value following the preceding theoretical reference, EasyLB is adaptive to wireless channel condition change and achieves fast convergence of load balancing after link failures.

Nanoscale Laponite as a Potential Shale Inhibitor in Water-Based Drilling Fluid for Stabilization of Wellbore Stability and Mechanism Study.

Shale hydration is the main reason causing wellbore instability in oil and gas drilling operations. In this study, nanoscale laponite as a shale inhibitor was employed to stabilize wellbores. The inhibition property of laponite suspensions was evaluated by an immersion experiment, linear swelling measurement, and a shale recovery test. Then the shale inhibition mechanism was studied by using capillary suction time (CST) measurement, a thixotropy study, plugging performance evaluation, and related theoretical analysis. Evaluation experiment results showed that laponite had a better inhibition property than widely used inhibitors of potassium chloride (KCl) and poly(ester amine) (PA). The mechanism study revealed that integration of several factors strengthened the inhibition property of laponite suspensions. Laponite nanoparticles could plug interlayer spaces of clays by electrostatic interaction to reduce water invasion; the "house of cards" structure of laponite suspensions enables large CST values and low free water contents; the excellent thixotropy of a laponite nanofluid could allow a nanofilm to form in order to reduce water invasion into the formation; the nanoscale laponite particles could substantially reduce the shale permeability and form less porous surfaces. Furthermore, laponite could considerably decrease the filtrate volume of the drilling fluid, while KCl and PA had negative influences on the properties of the drilling fluid. This approach described herein might provide an avenue to inhibit shale hydration.

Author Correction: Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry.

In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl benzoic acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl benzoic acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl benzoic acid derivative. All references to 2,5-dimethylpyrrolyl benzoic acid in the Letter have now been changed to reflect this.Although 2,5-dimethylpyrrolyl benzoic acid derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein-Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.

Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry.

Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR-Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl benzoic acid efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi's sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.

The herpes simplex virus 1 UL36USP deubiquitinase suppresses DNA repair in host cells via deubiquitination of proliferating cell nuclear antigen.

Herpes simplex virus 1 (HSV-1) infection manipulates distinct host DNA-damage responses to facilitate virus proliferation, but the molecular mechanisms remain to be elucidated. One possible HSV-1 target might be DNA damage-tolerance mechanisms, such as the translesion synthesis (TLS) pathway. In TLS, proliferating cell nuclear antigen (PCNA) is monoubiquitinated in response to DNA damage-caused replication fork stalling. Ubiquitinated PCNA then facilitates the error-prone DNA polymerase η (polη)-mediated TLS, allowing the fork to bypass damaged sites. Because of the involvement of PCNA ubiquitination in DNA-damage repair, we hypothesized that the function of PCNA might be altered by HSV-1. Here we show that PCNA is a substrate of the HSV-1 deubiquitinase UL36USP, which has previously been shown to be involved mainly in virus uptake and maturation. In HSV-1-infected cells, viral infection-associated UL36USP consistently reduced PCNA ubiquitination. The deubiquitination of PCNA inhibited the formation of polη foci and also increased cell sensitivity to DNA-damage agents. Moreover, the catalytically inactive mutant UL36C40A failed to deubiquitinate PCNA. Of note, the levels of virus marker genes increased strikingly in cells infected with wild-type HSV-1, but only moderately in UL36C40A mutant virus-infected cells, indicating that the UL36USP deubiquitinating activity supports HSV-1 virus replication during infection. These findings suggest a role of UL36USP in the DNA damage-response pathway.

Liposomes incorporating sodium deoxycholate for hexamethylmelamine (HMM) oral delivery: development, characterization, and in vivo evaluation.

Liposomes incorporating sodium deoxycholate (NaDC) were prepared by the method of reverse phase evaporation and used for drug delivery by the oral route. Hexamethylmelamine (HMM), an anti-tumor agent, was chosen as a model drug and encapsulated into liposomes incorporating NaDC (NaDC-Lip). Several properties of NaDC-Lip containing HMM (HMM NaDC-Lip), such as particle size, entrapment efficiency, pinacyanol chloride (PIN) spectral characteristics with various molar ratio of NaDC/PC, as well as the vesicle stability measurements with calcein were evaluated. In vivo, the area under the plasma concentration-time curve obtained from the pharmacokinetics study of HMM NaDC-Lip was found to be approximately 9.76- and 1.21-fold higher than that of HMM solution and HMM Lip, respectively, indicating that NaDC-Lip can be used as a potential carrier for oral drug administration.

[Clinical study of trimetazidine for myocardial protection in acute myocardial infarction].

OBJECTIVE: To assess the effect of trimetazidine as an adjunctive treatment to reperfusion therapy in acute myocardial infarction. METHODS: Sixty patients with acute myocardial infarction were randomized to receive trimetazidine (a loading dose of 60 mg followed by 20 mg 3 times daily) for 2 weeks (n = 32) or to be controls (n = 28). The loading dose was started early before the reperfusion therapy. Patients received intermittent ST-segment monitoring to assess the resolution of ST-segment deviation one hour after reperfusion therapy. Venous blood samples for measurement of malondialdehyde (MDA) and endothelin (ET-1) were taken immediately on admission and 1, 4, 8, 24 and 48 hours as well as 7 days after reperfusion. In-hospital and 3-months major adverse cardiac events were recorded. RESULTS: Blinded ST-segment analysis showed that there was a more marked return towards baseline one hour after reperfusion therapy in the trimetazidine group, than in the control group [change (7.14 +/- 3.50) mm vs (3.79 +/- 1.32) mm, P = 0.041]. The measurement of plasma MDA showed that, there was a significantly lower level in the trimetazidine group 4, 8, 24, 48 hours and 7 days after reperfusion (P < 0.05). The level of plasma ET-1 was significantly lower in the trimetazidine group 8 hours and 7 days after reperfusion (P < 0.05). There was no side effect due to trimetazidine. Clinical outcomes were similar between the two groups. CONCLUSIONS: Trimetazidine is effective for the resolution of ST-segment elevation. The effect of trimetazidine against malondialdehyde and ET-1 formation suggested that it might be the mechanism of the myocardial protection.

Molecular sensing with the tunnel junction of an Au nanogap in solution.

The tunnel junction of a gold nanogap was fabricated electrochemically for a molecular sensing device in solution. The tunnel junction was sensitive enough to detect the variation of a potential barrier within the nanogap, such as the chemical adsorption of molecules. By monitoring the variation of the tunneling current, which represents the change of a potential barrier due to molecular adsorption, the molecules could be detected.