Effects of polycyclic aromatic hydrocarbons on the gut-testis axis.

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds which are comprised of two or more fused benzene rings. As a typical environmental pollutant, PAHs are widely distributed in water, soil, atmosphere and food. Despite extensive researches on the mechanisms of health damage caused by PAHs, especially their carcinogenic and mutagenic toxicity, there is still a lack of comprehensive summarization and synthesis regarding the mechanisms of PAHs on the gut-testis axis, which represents an intricate interplay between the gastrointestinal and reproductive systems. Thus, this review primarily focuses on the potential forms of interaction between PAHs and the gut microbiota and summarizes their adverse outcomes that may lead to gut microbiota dysbiosis, then compiles the possible mechanistic pathways on dysbiosis of the gut microbiota impairing the male reproductive function, in order to provide valuable insights for future research and guide further exploration into the intricate mechanisms underlying the impact of gut microbiota dysbiosis caused by PAHs on male reproductive function.

Gas-Dependent Active Sites on Cu/ZnO Clusters for CH3OH Synthesis.

This study describes an instantaneously gas-induced dynamic transition of an industrial Cu/ZnO/Al2O3 catalyst. Cu/ZnO clusters become "alive" and lead to a promotion in reaction rate by almost one magnitude, in response to the variation of the reactant components. The promotional changes are functions of either CO2-to-CO or H2O-to-H2 ratio which determines the oxygen chemical potential thus drives Cu/ZnO clusters to undergo reconstruction and allows the maximum formation of Cu-Zn2+ sites for CH3OH synthesis.

Morphology evolution of the aluminum surface in a fluorine-containing environment.

The interaction between aluminum (Al) and F and O atoms is essential to understand the etching process of Al and alumina (Al2O3) by fluorine-containing gases. In addition, it also has an influence on the corrosion behavior of Al devices, e.g., the Al collector in lithium-ion batteries operates in fluorine-containing electrolytes. However, the understanding of the structural evolution of the Al surface by fluorination at the atomistic level still remains elusive. Here, the thermodynamic and kinetic behaviors of F adatoms as well as co-adsorbed F and O adatoms on typical Al surfaces have been systematically investigated by combining density functional theory (DFT) calculations, canonical Monte Carlo (CMC) simulations and reactive molecular dynamics (RMD) simulations. The results of DFT calculations indicate that there is a repulsion (about 0.07 eV on Al(111) and Al(110), and 0.7 eV on Al(100)) between the first nearest neighboring (1NN) F adatoms, while an attraction of 0.14 eV on Al(111) exists within a 1NN F-O pair. CMC simulations reveal that the configurations of co-adsorbed F and O adatoms on the Al(111) surface at medium to low temperature (<600 K) and low total coverage (<0.2 monolayer, ML) have F adatoms dispersed in the hexagonal islands of O adatoms due to the attraction within the O-O and F-O pairs and the repulsion between F adatoms. As the coverage increases, the surface undergoes serious deformation. The average 1NN coordination numbers (1st CN) of O-to-O, F-to-O and F-to-F are six, three and zero, respectively. As the temperature increases, the interactions among adsorbates begin to be disrupted: the 1st CNs of O-to-O and F-to-O decrease, while that of F-to-F increases. The O-F hexagonal pattern remains until above the Al melting temperature (>1200 K). For F adatoms, both their migration on the surface and the penetration into the subsurface are easier than those of O adatoms, confirmed by both the DFT and RMD simulations. Our study on the co-adsorbates with opposite lateral interactions is instructive for understanding the thermal etching of Al and Al2O3 by fluorine-containing compounds.

Coverage-dependent adsorption and dissociation of H2O on Al surfaces.

The adsorption and dissociation of H2O on Al surfaces including crystal planes and nanoparticles (ANPs) are systematically investigated by using density functional theory (DFT) calculations. H2O adsorption strength follows the order ANPs > Al(110) > Al(111) > Al(100). Due to the smaller cluster deformation caused by the moderate H2O adsorption, the relative magnitude of H2O adsorption strength on ANPs and crystal planes is opposite to the trend of adatoms like O* and/or N*. The energy barrier for the decomposition of H2O into H* and OH* is larger on ANPs than on crystal planes, and it decreases with the increasing cluster size. Due to the competition between the hydrogen (H) bonding among water molecules and the interaction between the water molecules and the substrate, the adsorption strength of H2O first increases and then decreases with the increase of water coverage. Moreover, each H2O molecule can efficiently form up to two H bonds with two H2O molecules. As a result, H2O molecules tend to aggregate into cyclic structures rather than chains on Al surfaces. Furthermore, the dissociation energy barrier of H2O drops with the increasing water coverage due to the presence of H bonds. Our results provide insight into interactions between water and Al, which can be extended to understand the interaction between water and other metal surfaces.

Interspecific differences in thermal tolerance landscape explain aphid community abundance under climate change.

A single critical thermal limit is often used to explain and infer the impact of climate change on geographic range and population abundance. However, it has limited application in describing the temporal dynamic and cumulative impacts of extreme temperatures. Here, we used a thermal tolerance landscape approach to address the impacts of extreme thermal events on the survival of co-existing aphid species (Metopolophium dirhodum, Sitobion avenae and Rhopalosiphum padi). Specifically, we built the thermal death time (TDT) models based on detailed survival datasets of three aphid species with three ages across a broad range of stressful high (34-40 °C) and low (-3∼-11 °C) temperatures to compare the interspecific and developmental stage variations in thermal tolerance. Using these TDT parameters, we performed a thermal risk assessment by calculating the potential daily thermal injury accumulation associated with the regional temperature variations in three wheat-growing sites along a latitude gradient. Results showed that M. dirhodum was the most vulnerable to heat but more tolerant to low temperatures than R. padi and S. avenae. R. padi survived better at high temperatures than Sitobion avenae and M. dirhodum but was sensitive to cold. R. padi was estimated to accumulate higher cold injury than the other two species during winter, while M. dirhodum accrued more heat injury during summer. The warmer site had higher risks of heat injury and the cooler site had higher risks of cold injury along a latitude gradient. These results support recent field observations that the proportion of R. padi increases with the increased frequency of heat waves. We also found that young nymphs generally had a lower thermal tolerance than old nymphs or adults. Our results provide a useful dataset and method for modelling and predicting the consequence of climate change on the population dynamics and community structure of small insects.

A novel nomogram for predicting cancer-specific survival in women with uterine sarcoma: a large population-based study.

BACKGROUND: Uterine sarcoma (US) is a rare malignant uterine tumor with aggressive behavior and rapid progression. The purpose of this study was to constructa comprehensive nomogram to predict cancer-specific survival (CSS) of patients with US-based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A retrospective population-based study was conducted using data from patients with US between 2010 and 2015 from the SEER database. They were randomly divided into a training cohort and a validation cohort ata 7-to-3 ratio. Multivariate Cox analysis was performed to identify independent prognostic factors. Subsequently, a nomogram was established to predict patient CSS. The discrimination and calibration of the nomogram were evaluated by the concordance index (C-index) and the area under the curve (AUC). Finally, net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the benefits of the new prediction model. RESULTS: A total of 3861 patients with US were included in our study. As revealed in multivariate Cox analysis, age at diagnosis, race, marital status, insurance record, tumor size, pathology grade, histological type, SEER stage, AJCC stage, surgery status, radiotherapy status, and chemotherapy status were found to be independent prognostic factors. In our nomogram, pathology grade had strongest correlation with CSS, followed by age at diagnosis and surgery status. Compared to the AJCC staging system, the new nomogram showed better predictive discrimination with a higher C-index in the training and validation cohorts (0.796 and 0.767 vs. 0.706 and 0.713, respectively). Furthermore, the AUC value, calibration plotting, NRI, IDI, and DCA also demonstrated better performance than the traditional system. CONCLUSION: Our study validated the first comprehensive nomogram for US, which could provide more accurate and individualized survival predictions for US patients in clinical practice.

Joint Intra/Inter-Slot Code Design for Unsourced Multiple Access in 6G Internet of Things.

Unsourced multiple access (UMA) is the technology for massive, low-power, and uncoordinated Internet-of-Things in the 6G wireless system, improving connectivity and energy efficiency on guaranteed reliability. The multi-user coding scheme design is a critical problem for UMA. This paper proposes a UMA coding scheme based on the T-Fold IRSA (irregular repetition slotted Aloha) paradigm by using joint Intra/inter-slot code design and optimization. Our scheme adopts interleave-division multiple access (IDMA) to enhance the intra-slot coding gain and the low-complexity joint intra/inter-slot SIC (successive interference cancellation) decoder structure to recover multi-user payloads. Based on the error event decomposition and density evolution analysis, we build a joint intra/inter-slot coding parameter optimization algorithm to minimize the SNR (signal-to-noise ratio) requirement at an expected system packet loss rate. Numerical results indicate that the proposed scheme achieves energy efficiency gain by balancing the intra/inter-slot coding gain while maintaining relatively low implementation complexity.

Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis.

BACKGROUND: The NLRP3-mediated pyroptosis, which could be regulated by miRNA-27a, is a key player in the development of depression. Isoliquiritin is a phenolic flavonoid compound that has been demonstrated to suppress NLRP3-mediated pyroptosis. However, it is still unknown whether isoliquiritin could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by stimulating miRNA-27a. Thus, in the current study, we explored the antidepressant activity of isoliquiritin and its underlying mechanism. METHODS: Expression of miRNA-27a in depressed patients or mice was measured using qRT-PCR. Luciferase reporter assay was performed to illustrate the link between miRNA-27a and SYK. Lipopolysaccharide (LPS) and chronic social defeat stress (CSDS) depression models were established to investigate the antidepressant actions of isoliquiritin. Changes in miRNA-27a/SYK/NF-κB axis and NLRP3-mediated pyroptosis were also examined. The role of miRNA-27a in isoliquiritin-related antidepressant effect was further investigated by using miRNA-27a inhibitors and mimics of miRNA-27a. RESULTS: Our results showed the miRNA-27a expression was downregulated in the serum of depressed patients, and decreased serum and hippocampus expression of miRNA-27a were observed in rodent models of depression. SYK gene expression was significantly reduced by miRNA-27a mimic incubation. Isoliquiritin profoundly attenuated LPS or CSDS-induced depressive symptoms, as well as CSDS-induced anxiety behavior. In the hippocampus, LPS and CSDS decreased miRNA-27a mRNA expression; increased the protein levels of SYK, p-NF-κB, and NLRP3: cleaved Caspase-1, IL-1ß, and GSDMD-N: and elevated the concentration of IL-1ß, IL-6, and TNF-α, which were all restored by isoliquiritin administration. Meanwhile, isoliquiritin upregulated the hippocampal NeuN protein level, improved the survival and morphology of neurons, and decreased pyroptosis-related neuronal cell death. Moreover, isoliquiritin protected primary microglia against LPS and adenosine triphosphate (ATP) elicited NLRP3 inflammasome activation in vitro, evidenced by declined protein levels of p-NF-κB, NLRP3; cleaved Caspase-1, IL-1ß, and GSDMD-N; upregulated miRNA-27a mRNA expression; and decreased the mRNA and protein levels of SYK. Nevertheless, miRNA-27a inhibitors significantly reversed isoliquiritin-generated therapeutic efficacy in CSDS mice and in vitro. Furthermore, the cytoprotective effect of isoliquiritin was similar to that of miRNA-27a mimics in LPS and ATP-treated primary microglia. Taken together, these findings suggest that isoliquiritin possesses potent antidepressant property, which requires miRNA-27a/SYK/NF-κB axis controlled decrease of pyroptosis via NLRP3 cascade.

Screening for proteins related to the biosynthesis of hispidin and its derivatives in Phellinus igniarius using iTRAQ proteomic analysis.

BACKGROUND: Hispidin (HIP) and its derivatives, a class of natural fungal metabolites, possess complex chemical structures with extensive pharmacological activities. Phellinus igniarius, the most common source of HIP, can be used as both medicine and food. However, the biosynthetic pathway of HIP in P. igniarius remains unclear and we have a limited understanding of the regulatory mechanisms related to HIP. In this work, we sought to illustrate a biosynthesis system for hispidin and its derivatives at the protein level. RESULTS: We found that tricetolatone (TL) is a key biosynthetic precursor in the biosynthetic pathway of hispidin and that its addition led to increased production of hispidin and various hispidin derivatives. Based on the changes in the concentrations of precursors and intermediates, key timepoints in the biosynthetic process were identified. We used isobaric tags for relative and absolute quantification (iTRAQ) to study dynamic changes of related proteins in vitro. The 270 differentially expressed proteins were determined by GO enrichment analysis to be primarily related to energy metabolism, oxidative phosphorylation, and environmental stress responses after TL supplementation. The differentially expressed proteins were related to ATP synthase, NAD binding protein, oxidoreductase, and other elements associated with electron transfer and dehydrogenation reactions during the biosynthesis of hispidin and its derivatives. Multiple reaction monitoring (MRM) technology was used to selectively verify the iTRAQ results, leading us to screen 11 proteins that were predicted to be related to the biosynthesis pathways. CONCLUTION: These findings help to clarify the molecular mechanism of biosynthesis of hispidin and its derivatives and may serve as a foundation for future strategies to identify new hispidin derivatives.

High-Preservation Single-Cell Operation through a Photo-responsive Hydrogel-Nanopipette System.

Single-cell and in situ cell-based operation with nanopipette approach offers a possibility to elucidate the intracellular processes and may aid the improvement of therapy efficiency and precision. We present here a photo-responsive hydrogel-nanopipette hybrid system that can achieve single-cell operation with high spatial/temporal resolution and negligible cell damage. This strategy overcomes long-time obstacles in nanopipette single-cell studies as high electric potential (ca. 1000 mV) or organic solvent is always used during operations, which would inevitably impose disturbance and damage to targeted cells. The light-triggered system promotes a potential-free, non-invasive single-cell injection, resulting in a well-retained cell viability (90 % survival rate). Moreover, the photo-driven injection enables a precisely dose-controllable single-cell drug delivery. Significantly reduced lethal doses of doxorubicin (163-217 fg cell-1 ) are demonstrated in corresponding cell lines.

Dissociative chemisorption of O2 on Agn and Agn-1Ir (n = 3-26) clusters: a first-principle study.

Understanding the interactions between O2 and small metal clusters is of great importance in exploring heterogeneous catalysis particularly involving an oxidation reaction. We herein present the dissociative chemisorption of O2 on Agn and Agn-1Ir clusters (n = 3-26) by using density functional theory calculations. Combining a particle swarm optimization algorithm and a minima hopping method, we have optimized and obtained stable geometric structures of Agn and Agn-1Ir clusters without and with O2 adsorption. Some important physical parameters, including bond length, adsorption energy, dissociation barriers and bader charge, have been systematically calculated for appraising the stability and reactivity of Agn and Agn-1Ir clusters. It is found that the dopant Ir atom can largely enhance the stability and promote the O2 dissociation, especially on small Agn-1Ir clusters (n = 3-10). It is mainly attributed to the dopant Ir atom being completely exposed outside the Ag atoms. For O2 adsorption and dissociation on large Agn-1Ir clusters (n = 11-26), the dissociation barriers are much higher due to the dopant Ir emerging into the core of Agn-1Ir clusters, which is very similar to those on large Agn (n = 11-26). Microkinetic simulation results provide direct evidence for high reaction temperature and pressure effects on improving O2 dissociation on Agn and Agn-1Ir clusters especially for small clusters (n < 10). It is found that the Ag5Ir cluster is the most suitable nanocluster for promoting O2 dissociation at the given reaction temperatures and pressures. Our theoretical work is helpful for the rational design of doped silver nanocluster catalysts in future experiments.

Monitoring Hydrogen Evolution Reaction Catalyzed by MoS2 Quantum Dots on a Single Nanoparticle Electrode.

Hydrogen evolution reaction (HER) catalyzed by molybdenum sulfide quantum dots (MoS2 QDs) has attracted extensive attention in the energy field. Monitoring HER catalyzed by MoS2 QDs based on a glass nanopore with an electrochemically confined effect was proposed for the first time. MoS2 QDs inside the glass nanopore is driven toward the orifice of the nanopore and bonded with the Ag nanoparticles (Ag NPs) to form a single nanocomposite. When enough voltage is applied across the orifice, the single Ag NP acts as a single nanoparticle electrode to conduct the electrochemically bipolar reaction on its two extremities. In the process, HER is catalyzed by MoS2 QDs, and Ag NPs are oxidized at the same time. The appearance of blockages on the elevated ionic current is attributed to the generation of a H2 bubble. Furthermore, by analyzing the modulations in the ionic current oscillation, the frequency of hydrogen bubble generation that is related to the catalytic efficiency of MoS2 QDs could be estimated. The results reveal the capability of the glass nanopore for the real-time monitoring electrocatalytic behavior, which makes the glass nanopore an ideal candidate to further reveal the heterogeneity of catalytic capability at the single particle level.

A nomogram for determining the disease-specific survival in Ewing sarcoma: a population study.

BACKGROUND: We aimed to develop and validate a nomogram for predicting the disease-specific survival of Ewing sarcoma (ES) patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify ES from 1990 to 2015, in which the data was extracted from 18 registries in the US. Multivariate analysis performed using Cox proportional hazards regression models was performed on the training set to identify independent prognostic factors and construct a nomogram for the prediction of the 3-, 5-, and 10-year survival rates of patients with ES. The predictive values were compared by using concordance indexes (C-indexes), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS: A total of 2,643 patients were identified. After multivariate Cox regression, a nomogram was established based on a new model containing the predictive variables of age, race, extent of disease, tumor size, and therapy of surgery. The new model provided better C-indexes (0.684 and 0.704 in the training and validation cohorts, respectively) than the model without therapy of surgery (0.661 and 0.668 in the training and validation cohorts, respectively). The good discrimination and calibration of the nomogram were demonstrated for both the training and validation cohorts. NRI and IDI were also improved. Finally, DCA demonstrated that the nomogram was clinically useful. CONCLUSION: We developed a reliable nomogram for determining the prognosis and treatment outcomes of patients with ES in the US. However, the proposed nomogram still requires external data verification in future applications, especially for regions outside the US.

Licorisoflavan A Exerts Antidepressant-Like Effect in Mice: Involvement of BDNF-TrkB Pathway and AMPA Receptors.

Depression is a highly debilitating and life-threatening psychiatric disorder. The classical antidepressants are still not adequate due to undesirable side effects. Therefore, the development of new drugs for depression treatment is an urgent strategic to achieving clinical needs. Licorisoflavan A is a bioactive ingredient isolated from Glycyrrhizae Radix and has been recently reported for neuroprotective effects. In this study, the antidepressant-like effect and neural mechanism of licorisoflavan A were explored. In the mice behavioral despair test, we observed that licorisoflavan A exhibited powerful antidepressant-like effect in forced swimming test (FST), tail suspension test (TST), without affecting locomotor activity in open field test (OFT). Additionally, licorisoflavan A administration significantly restored Chronic mild stress (CMS)-induced changes in sucrose preference test (SPT), FST, and TST, without altering the locomotion in OFT. In chronical-stimulated mice, the licorisoflavan A treatment effectively attenuated the expressions of Brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), the phosphorylations of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK)-1/2, eukaryotic elongation factor 2 (eEF2), mammalian target of rapamycin (mTOR), initiation factor 4E-binding protein 1 (4E-BP-1), and p70 ribosomal protein S6 kinase (p70S6K) in hippocampus of CMS-induced mice. Additionally, licorisoflavan A could reverse the decreases in synaptic proteins post-synaptic density protein 95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) caused by CMS, and its antidepressant-like effect was blocked by the AMPA receptor antagonist NBQX. These findings served as preclinical evidence that licorisoflavan A exerted potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors. Licorisoflavan A might be used as a potential medicine against depression-like disorder.

miR-206 Inhibits Cell Proliferation and Extracellular Matrix Accumulation by Targeting Hypoxia-Inducible Factor 1-alpha (HIF-1α) in Mesangial Cells Treated with High Glucose.

BACKGROUND The goal of this study was to investigate the expression of miR-206 in human glomerular mesangial cells (hMCs) treated by exposure to high glucose (HG) levels, to assess the influence of miR-206 on the proliferation and extracellular matrix (ECM) deposition of hMCs, and to investigate the potential mechanisms of action. MATERIAL AND METHODS The level of miR-206 was detected by RT-qPCR. MTT assay and colony formation assay were used to assess hMCs cell proliferation ability. Western blotting was carried out to measure the expression of related proteins. Bioinformatics software (http://www.targetscan.org) was used to predict the potential target genes of miR-206, and dual-luciferase reporter assay was used to confirm this prediction. RESULTS Our results suggest that the level of miR-206 was downregulated in HG-treated hMCs. Cell proliferation was promoted in HG-induced hMCs, while this phenomenon was significantly reversed with miR-206 mimics. miR-206 mimics significantly enhanced p21 expression and decreased cyclin D1 and CDK2 expressions, but the opposite was found in HG-induced hMCs. Moreover, the level of ECM proteins was notably increased in hMCs treated with HG, which was also significantly reversed by miR-206 mimics. miR-206 inhibitor had the opposite effects. Furthermore, HIF-1alpha was found to be a direct target of miR-206, and was negatively regulated by miR-206 in hMCs. miR-206 can target HIF-1alpha to modulate cell proliferation and ECM accumulation. CONCLUSIONS Collectively, our results suggest that miR-206 plays a vital role in HG-treated hMCs through inhibiting cell proliferation and ECM accumulation, partly via targeting HIF-1alpha.

Development and validation of a nomogram containing the prognostic determinants of chondrosarcoma based on the Surveillance, Epidemiology, and End Results database.

BACKGROUND: We aimed to develop and validate a reliable nomogram for predicting the disease-specific survival (DSS) of chondrosarcoma patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2004 to 2015 to identify cases of histologically confirmed chondrosarcoma. Multivariate Cox regression analysis was performed to identify independent prognostic factors and construct a nomogram for predicting the 3- and 5-year DSS rates. Predictive values were compared between the new model and the American Joint Committee on Cancer (AJCC) staging system using concordance indexes (C-indexes), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS: Multivariate Cox regression identified 1180 patients, who were used to establish a nomogram based on a new model containing the predictive variables of age, socioeconomic status, tumor size, surgery status, chemotherapy status, and AJCC staging. In the nomogram, age at diagnosis is the factor with the highest risk, followed by AJCC stage IV and tumor size > 100 mm. Both the C-index and the calibration plots demonstrated the good performance of the nomogram. Moreover, both NRI and IDI were improved compared to the AJCC staging system, and also DCA demonstrated that the nomogram is clinically useful. CONCLUSION: We have developed a reliable nomogram for determining the prognosis and treatment outcomes of chondrosarcoma patients that is superior to the traditional AJCC staging system.

Abnormal subsurface hydrogen diffusion behaviors in heterogeneous hydrogenation reactions.

Hydrogen adsorption and diffusion behaviors on noble metal model catalyst surfaces and into the subsurfaces are of paramount significance in the exploration of novel heterogenous catalytic hydrogenation reactions. We present an in-depth study of hydrogen adsorption on and diffusion into the subsurfaces of three typical 5d noble metals from three-dimensional electronically adiabatic potential energy surfaces (PESs) by interpolating plenty of ab initio density functional theory (DFT) configuration-energy points. The surfaces and subsurfaces regions of the relaxed Ir(100) and (111), Pt(100) and (111), and Au(100) and (111) surfaces, are, respectively, taken into account. For hydrogen adsorption on the (100) surfaces, the lowest adsorption energy site is the Bridge site, instead of the traditional Hollow site. Hydrogen prefers to follow the indirect pathway with a lower diffusion barrier, in the competition with the direct pathway with much higher diffusion barrier. For hydrogen diffusion on the (111) surfaces, hydrogen follows the pathway from Top site to fcc site on the surface and prefers an up-down direct pathway into the subsurface. Importantly, the nudged elastic band (NEB) based on the PESs can reproduce those results calculated from the NEB(DFT) very well. The developed highly-accurate and efficient approach based on the PESs helps us to further investigate the more complex reactant diffusion dynamics at surfaces.

[Network pharmacology of flavonoids in Sophora alopecuroides].

The aim of this paper was to investigate the potential pharmacological effect of flavonoids in Sophora alopecuroides by network pharmacology. This study predicted the potential targets of 11 flavonoids of S. alopecuroides with help of reversed pharmacophore matching target recognition service platform (PharmMapper). The pathway information was acquired from DAVID and KEGG databases. Cytoscape software was used to construct the "ingredient-target-pathway" network of flavonoids active components of S. alopecuroides. The flavonoids active components of S. alopecuroides play anti-inflammatory, blood sugar regulating and other pharmacological effects by regulating 62 targets (such as INSR，KDR，MET) and intervening 44 pathways, such as B cell receptor signaling pathway, insulin signaling pathway, neurotrophin signaling pathway, and T cell receptor signaling pathway. In this study, the mechanism of "muti components-multitargets-multiple pathway" of flavonoids was studied. It reflects the multi-components, multi-targets and multiple pathway features of traditional Chinese medicine. Meanwhile, it provides a scientific basis for the elucidation the mechanism of S. alopecuroides as a medicine, and the development and utilization resources of S. alopecuroides.

A 30 nm Nanopore Electrode: Facile Fabrication and Direct Insights into the Intrinsic Feature of Single Nanoparticle Collisions.

Clarifying the hidden but intrinsic feature of single nanoparticles by nanoelectrochemistry could help understand its potential for diverse applications. The uncontrolled interface and bandwidth limitation in the electrochemical measurement put the obstacle in single particle collision. Here, we demonstrate a well-defined 30 nm nanopore electrode with a rapid chemical-electrochemical fabrication method which provides a high reproducibility in both size and performance. A capacitance-based detection mechanism is demonstrated to achieve a high current resolution of 0.6 pA ±0.1 pA (RMS) and a high the temporal resolution of 0.01 ms. By utilizing this electrode, the dynamic interactions of every single particle in the mixture could be directly read during the collision process. The collision frequency is two orders of magnitude higher than previous reports, which helps reveal the hidden features of nanoparticles during the complex and multidimensional interaction processes.

Wireless Bipolar Nanopore Electrode for Single Small Molecule Detection.

Solid-state nanopore-based techniques have become a promising strategy for diverse single molecule detections. Owing to the challenge in well and rapid fabrication of solid-state nanopores with the diameter less than 2 nm, small molecule detection is hard to be addressed by existing label-free nanopore methods. In this work, we for the first time propose a metal-coated wireless nanopore electrode (WNE) which offers a novel and generally accessible detection method for analyzing small molecules and ions at the single molecule/ion level. Here, a silver-coated WNE is developed as a proof-of-principle model which achieves the detection the self-generated H2, the smallest known molecule, and Ag+ at single molecule/ion level by monitoring the enhanced ionic signatures. Under a bias potential of -800 mV, the WNE could accomplish the distinction of as low as 14 H2 molecules and 28 Ag+ from one spike signal. The finite element simulation is introduced to suggest that the generation of H2 at the orifice of the WNE results in the enhanced spike of ionic current. As a proof-of-concept experiment, the WNE is further utilized to directly detect Hg2+ from 100 pM to 100 nM by monitoring the frequency of the spike signals. This novel nanoelectrode provides a brand new label-free, ultrasensitive, and simple detection mechanism for various small molecules/ions detection, especially for redox analytes.