Inhibition of KDM5B participates in immune microenvironment remodeling in pancreatic cancer by inducing STING expression.

OBJECTIVE: This study aims to investigate the effect of lysine demethylase 5B (KDM5B)-mediated dimethyl-lysine 4 histone H3 (H3K4me2) demethylation on immune microenvironment remodeling in pancreatic cancer. METHODS: Pan 02 mouse pancreatic cancer cell lines were cultured and used to establish tumor model in vivo. RT-qPCR and Western blot were used to detect the expression of stimulator of interferon gene (STING) and KDM5B in pancreatic cancer tissues and Pan 02 cells. The specific demethylation domain of KDM5B was detected by isothermal titration calorimetry binding assay. The regulatory roles of KDM5B in cell apoptosis and remodeling of immune microenvironment in vitro and in vivo were explored after loss-of functions in KDM5B. RESULTS: KDM5B was highly expressed but STING was poorly expressed in pancreatic cancer tissues and Pan 02 cells. After knockdown of KDM5B, CD8+ T cells recognized and killed Pan 02 cells, which promoted the infiltration of CD8+ T cells in Pan 02 cells, thus improving the anti-tumor ability. The PHD domain in KDM5B specifically bound to H3K4me2 peptide and inhibition of KDM5B induced STING expression. Knockdown of KDM5B up-regulated STING expression to promote apoptosis, thus regulating the immune microenvironment and inhibiting the growth of tumor in mice. Meanwhile, knockdown of KDM5B and STING simultaneously counteracted the knockdown effect of KDM5B. CONCLUSION: Inhibition of KDM5B can promote the expression of STING through H3K4me2 demethylation, which promoted the recognition and killing of Pan 02 cells by CD8+ T cells, thus improving the anti-tumor ability and regulating the immune microenvironment.

Investigation of Pre-service Teachers' Conceptions of the Nature of Science Based on the LDA Model.

This study used the Latent Dirichlet Allocation (LDA) topic model to analyze pre-service teachers' views on the nature of science (NOS). This approach can be used to automate the classification of documents, and at the same time, the researcher does not need to deduce with a NOS framework prior to evaluation. Participants were 155 pre-service teachers studying at the Shandong Normal University in China. To gather our data, we used an open questionnaire, namely, the Views of Nature of Science Questionnaire-Form C (VNOS-C). LDA topic modeling was used to classify the document, which was divided into 12 topics. By comparing the LDA topic modeling results with the theoretical framework behind the VNOS-C questionnaire, we categorized these 12 topics into eight descriptive aspects of the NOS: The Empirical Nature of Scientific Knowledge, Observation, Inference, and Theoretical Entities in Science, Scientific Theories and Laws, The Theory-Laden Nature of Scientific Knowledge, The Social and Cultural Embeddedness of Scientific Knowledge, The Myth of The Scientific Method, The Tentative Nature of Scientific Knowledge, and The Nature of Scientific Theory. The results show that pre-service teachers usually hold naive or mixed views of the NOS. In addition, each aspect of NOS is not independent of each other but interrelated and influencing each other. In the future, more consideration can be given to the relationship between each aspect of NOS.

Accurate potential energy surface of H2S+(X 2 A″) via extrapolation to the complete basis set limit and its use in dynamics study of S + ( D 2 ) + H 2 ( X 1 Σ g + ) reaction.

The single-sheeted potential energy surface (PES) of H 2 S + ( X 2 A ' ' ) is developed based on the ab initio energies calculated by the multi-reference configuration interaction method including the Davidson correction. All the ab initio energies are first calculated using aug-cc-pVQdZ and aug-cc-pV5dZ basis sets, which are then extrapolated to the complete basis set (CBS) limit. A switching function is developed to model the transition of S + D 2 to S + S 4 . The many-body expansion formalism is employed to obtain the H 2 S + ( X 2 A ' ' ) PES by fitting such CBS energies and the root-mean square derivation is 0.0367 eV. The topographical features of the present PES are examined in detail, which are well consistent with previous studies. The quasiclassical trajectory method is subsequently utilized to study the S + D 2 + H 2 ( X 1 Σ g + ) → S H + ( X 3 Σ - ) + H ( S 2 ) reaction. The capture time, integral cross sections, and rovibrational distributions are calculated. By examining the capture time, it can be concluded that the title reaction is mainly controlled by the indirect mechanism for lower collision energies, while the direct and indirect mechanisms coexist and the latter plays a dominant role for higher collision energies.

Diagnostic utility of plasma lncRNA small nucleolar RNA host gene 1 in patients with hepatocellular carcinoma.

Long non­coding RNAs (lncRNAs) offer great potential as cancer biomarkers. Owing to the limited sensitivity and specificity of α­fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma (HCC), the present study used an lncRNA microarray to screen aberrantly expressed lncRNAs in HCC tissues. Subsequently, the expression profile of the target lncRNAs was investigated in plasma from patients with HCC or hepatitis B virus­positive chronic hepatitis and cirrhosis (HCH), as well as from healthy volunteers. A total of six aberrantly expressed lncRNAs were identified in HCC tissues and corresponding normal tissues, from which only small nucleolar RNA host gene 1 (SNHG1) expression in HCC tissues demonstrated a good correlation with those in plasma from HCC patients. Subsequent analysis revealed that high plasma SNHG1 expression levels were correlated with tumor size, TNM stage and AFP levels. Receiver operating characteristic analysis demonstrated that SNHG1 yields an excellent diagnostic ability to differentiate between patients with HCC and unaffected control patients, which was superior to that of AFP. The combination of SNHG1 with AFP may be able to distinguish HCC from HCH or healthy volunteers with the area under the curve values of 0.86 and 0.97, respectively. In summary, it was demonstrated that plasma SNHG1 has great potential as a sensitive and reliable biomarker for the diagnosis of HCC.

Third-harmonic generation from gold nanowires of rough surface considering classical nonlocal effect.

We demonstrate that the nonlocal dielectric response of metal, comparing with the traditional local model, will significantly boost the third-order harmonic generation (THG) from gold nanowires of rough surface by a factor of several orders of magnitude. The enhancement is probably due to the penetrated field into the fine nanostructures on the metal surface in nonlocal model. The anisotropy THG efficiency versus the angle of incidence is also demonstrated due to the inhomogeneous surface morphology. The possible ways to verify the nonlocal effect to the THG are demonstrated. The results have a general significance in explaining the experimental observations.

Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor.

Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array.

Globally accurate potential energy surface for the ground-state HCS(X2A') and its use in reaction dynamics.

A globally accurate many-body expansion potential energy surface is reported for HCS(X2A') by fitting a wealth of accurate ab initio energies calculated at the multireference configuration interaction level using aug-cc-pVQZ and aug-cc-pV5Z basis sets via extrapolation to the complete basis set limit. The topographical features of the present potential energy surface are examined in detail and is in good agreement with the raw ab initio results, as well as other theoretical results available in literatures. By utilizing the potential energy surface of HCS(X2A'), the dynamic studies of the C(3P) + SH(X2Π) → H(2S) + CS(X1∑+) reaction has been carried out using quasi-classical trajectory method.

State-to-State Quantum Dynamics of Reactions O((3)P) + HD (v = 0-1, j = 0) → OH+D and OD+H: Reaction Mechanism and Vibrational Excitation.

Time-dependent quantum wave packet dynamics calculations have been performed in order to characterize the dynamics and mechanism of O((3)P) + HD (v = 0-1, j = 0) → OH+D and OD+H reactive collisions using the adiabatic potential energy surface by Rogers et al. [J. Phys. Chem. A 2000, 104, 2308] Special attention has been paid to the calculations and discussion of the state resolved integral and differential cross sections and the product state distributions. In addition, the intramolecular isotopic branching ratio has been determined. The results revealed that the OD + H is the favored product channel and the product OH has the same quantum number v as the reactant HD. For low collision energy, the product angular distributions concentrate in the backward region being consistent with a rebounding mechanism. In the case of higher collision energy, the stripping collisions with larger impact parameters tend to produce sideways and forward scatterings, especially for the HD vibrationally excited state. The cross section and intramolecular isotopic branching ratio are in agreement with the previous theoretical results. A cartoon depiction collision model is built and works well for our calculation results.

Graphene-Based Flexible and Transparent Tunable Capacitors.

We report a kind of electric field tunable transparent and flexible capacitor with the structure of graphene-Bi1.5MgNb1.5O7 (BMN)-graphene. The graphene films with low sheet resistance were grown by chemical vapor deposition. The BMN thin films were fabricated on graphene by using laser molecular beam epitaxy technology. Compared to BMN films grown on Au, the samples on graphene substrates show better quality in terms of crystallinity, surface morphology, leakage current, and loss tangent. By transferring another graphene layer, we fabricated flexible and transparent capacitors with the structure of graphene-BMN-graphene. The capacitors show a large dielectric constant of 113 with high dielectric tunability of ~40.7 % at a bias field of 1.0 MV/cm. Also, the capacitor can work stably in the high bending condition with curvature radii as low as 10 mm. This flexible film capacitor has a high optical transparency of ~90 % in the visible light region, demonstrating their potential application for a wide range of flexible electronic devices.

Graphene/Cu nanoparticle hybrids fabricated by chemical vapor deposition as surface-enhanced Raman scattering substrate for label-free detection of adenosine.

We present a graphene/Cu nanoparticle hybrids (G/CuNPs) system as a surface-enhanced Raman scattering (SERS) substrate for adenosine detection. The Cu nanoparticles wrapped by a monolayer graphene shell were directly synthesized on flat quartz by chemical vapor deposition in a mixture of methane and hydrogen. The G/CuNPs showed an excellent SERS enhancement activity for adenosine. The minimum detected concentration of the adenosine in serum was demonstrated as low as 5 nM, and the calibration curve showed a good linear response from 5 to 500 nM. The capability of SERS detection of adenosine in real normal human urine samples based on G/CuNPs was also investigated and the characteristic peaks of adenosine were still recognizable. The reproducible and the ultrasensitive enhanced Raman signals could be due to the presence of an ultrathin graphene layer. The graphene shell was able to enrich and fix the adenosine molecules, which could also efficiently maintain chemical and optical stability of G/CuNPs. Based on the G/CuNPs system, the ultrasensitive SERS detection of adenosine in varied matrices was expected for the practical applications in medicine and biotechnology.