Direct visualization of electric current induced dipoles of atomic impurities

Learning the electron scattering around atomic impurities is a fundamental step to fully understand the basic electronic transport properties of realistic conducting materials. Although many efforts have been made in this field for several decades, atomic scale transport around single point-like impurities has yet been achieved. Here, we report the direct visualization of the electric current induced dipoles around single atomic impurities in epitaxial bilayer graphene by multi-probe low temperature scanning tunneling potentiometry as the local current density is raised up to around 25 A/m, which is considerably higher than that in previous studies. We find the directions of these dipoles which are parallel or anti-parallel to local current are determined by the charge polarity of the impurities, revealing the direct evidence for the existence of the carrier density modulation effect proposed by Landauer in 1976. Furthermore, by $in$ $situ$ tuning local current direction with contact probes, these dipoles are redirected correspondingly. Our work paves the way to explore the electronic quantum transport phenomena at single atomic impurity level and the potential future electronics toward or beyond the end of Moore's Law

Investigation of the prevalence and clinical implications of ERBB2 exon 16 skipping mutations in Chinese pan-cancer patients

BackgroundAlthough rare, ERBB2 exon 16 skipping mutations (ERBB2ΔEx16) have been implicated in resistance to anti-HER2 and anti-EGFR targeted agents. Our study investigated the prevalence and clinical significance of ERBB2ΔEx16 in Chinese pan-cancer patients.MethodsWe retrospectively screened 40996 patients, spanning 19 cancer types, who had available genomic profiles acquired with DNA-based next-generation sequencing (NGS). We characterized the clinical and molecular features of the ERBB2ΔEx16-positive patients. Furthermore, we also analyzed a pan-cancer dataset from the Cancer Genome Atlas (TCGA; n=8705).ResultsA total of 22 patients were detected with ERBB2ΔEx16, resulting in an overall prevalence rate of 0.054% (22/40996). Of them, 16 patients had lung cancer (LC; 0.05%, 16/30890), five patients had gastric cancer (GC; 0.35%, 5/1448), and one patient had ovarian cancer (0.12%, 1/826). Among the 16 LC patients, ERBB2ΔEx16 was detected in four treatment-naïve EGFR/ALK-negative patients and 12 EGFR-positive patients after the onset of resistance to EGFR tyrosine kinase inhibitors (TKIs). The treatment-naïve patients harbored no LC-associated oncogenic drivers except ERBB2 amplification, suggesting a potential oncogenic role for ERBB2ΔEx16. Consistently, ERBB2ΔEx16+ patients from TCGA data also carried no known drivers despite various concurrent alterations. In the 12 EGFR TKI-resistant LC patients, relative variant frequencies for ERBB2ΔEx16 were lower than in untreated patients, suggesting ERBB2ΔEx16 as secondary alterations following TKI treatment and thereby implicating ERBB2ΔEx16 in mediating therapeutic resistance.ConclusionsOur study identified an overall ERBB2ΔEx16 prevalence rate of 0.054% and provided insights into the clinical implications of ERBB2ΔEx16 in Chinese pan-cancer patients

Thioredoxin Glutathione Reductase as a Novel Drug Target: Evidence from Schistosoma japonicum

Background: Schistosomiasis remains a major public health concern affecting billions of people around the world. Currently, praziquantel is the only drug of choice for treatment of human schistosomiasis. The emergence of drug resistance to praziquantel in schistosomes makes the development of novel drugs an urgent task. Thioredoxin glutathione reductase (TGR) enzymes in Schistosoma mansoni and some other platyhelminths have been identified as alternative targets. The present study was designed to confirm the existense and the potential value of TGR as a target for development of novel antischistosomal agents in Schistosoma japonicum, a platyhelminth endemic in Asia. Methods and Findings: After cloning the S. japonicum TGR (SjTGR) gene, the recombinant SjTGR selenoprotein was purified and characterized in enzymatic assays as a multifunctional enzyme with thioredoxin reductase (TrxR), glutathione reductase (GR) and glutaredoxin (Grx) activities. Immunological and bioinformatic analyses confirmed that instead of having separate TrxR and GR proteins in mammalian, S. japonicum only encodes TGR, which performs the functions of both enzymes and plays a critical role in maintaining the redox balance in this parasite. These results were in good agreement with previous findings in Schistosoma mansoni and some other platyhelminths. Auranofin, a known inhibitor against TGR, caused fatal toxicity in S. japonicum adult worms in vitro and reduced worm and egg burdens in S. japonicum infected mice. Conclusions: Collectively, our study confirms that a multifunctional enzyme SjTGR selenoprotein, instead of separate Trx

Circ_0020123 promotes non‐small cell lung cancer progression via miR‐146a‐5p mediated regulation of EIF4G2 expression

Abstract Background Circular RNAs (circRNAs) have been reported to be involved in the initiation and development of cancers. The aim of this study was to determine the role of a circRNA, circ_0020123, in the development of non‐small cell lung cancer (NSCLC). Methods The expression of circ_0020123, microRNA‐146a‐5p (miR‐146a‐5p), and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) mRNA was detected by quantitative real‐time PCR (qPCR). Western blot was used to determine the protein levels of cyclin D1, Bax, MMP‐9, and EIF4G2. Cell proliferation was assessed by cell counting kit‐8 (CCK‐8) assay and colony formation assay. Flow cytometry assay was applied to determine cell cycle apoptosis. Cell migration and invasion were assessed using transwell assay. The potential relationship between miR‐146a‐5p and circ_0020123 or EIF4G2 was ascertained by dual‐luciferase reporter assay and RIP assay. The role of circ_0020123 in vivo was explored by xenograft assay. Results Circ_0020123 was upregulated in NSCLC, and circ_0020123 knockdown repressed proliferation, migration, and invasion of NSCLC cells. Circ_0020123 targeted miR‐146a‐5p, and miR‐146a‐5p inhibitor reversed the effects of circ_0020123 knockdown on NSCLC cells. In addition, miR‐146a‐5p suppressed cell proliferation, migration, and invasion by targeting EIF4G2. Moreover, the antitumor role of circ_0020123 knockdown was verified in vivo. Conclusion Knockdown of circ_0020123 inhibited NSCLC cell progression and tumor growth by targeting the miR‐146a‐5p/EIF4G2 axis

Spatial Distribution Characteristics and Influencing Factors of the Success or Failure of China’s Overseas Arable Land Investment Projects—Based on the Countries along the “Belt and Road”

As globalization continues, overseas arable land investment is becoming a viable option for China to alleviate its agricultural growth constraints, and the “Belt and Road” initiative offers plenty of opportunities for China to invest in overseas arable land. This study used data from the Land Matrix, KOF, World Bank, CEPII, UNCTAD and other databases to analyze the spatial distribution characteristics and factors influencing the success or failure of China’s overseas farmland investment projects in countries along the “Belt and Road” project through spatial analysis and the Logit model. The results show that North America has the largest share of production versus contracted acreage in current acreage investment cases, and Asian projects have the highest success rate. Both successful and failed projects in China regarding arable land investment are highly correlated spatially and characterized by a strong concentration and low uniformity of distribution, with differences in the degree of concentration in Asia, Africa and other regions. The contracted area, host country participation and host country resource endowment, business environment and institutional quality have significant, inverted “U-shaped”, negative and positive effects on project success, respectively. In addition, the involvement of the host country has a significant negative impact on the success of investment projects in Africa, and the length of investment and the type of investment purpose have a significant positive and negative impact on the success of investment projects in Asian countries. Therefore, China’s overseas arable land investment should be based on a full examination of existing investment projects in each country, the selection of host countries with abundant resource endowments and a good business environment and institutional environment and the adoption of a model suitable for each location to carry out investments according to local conditions

Spatial Distribution Characteristics and Influencing Factors of the Success or Failure of China’s Overseas Arable Land Investment Projects—Based on the Countries along the “Belt and Road”

As globalization continues, overseas arable land investment is becoming a viable option for China to alleviate its agricultural growth constraints, and the “Belt and Road” initiative offers plenty of opportunities for China to invest in overseas arable land. This study used data from the Land Matrix, KOF, World Bank, CEPII, UNCTAD and other databases to analyze the spatial distribution characteristics and factors influencing the success or failure of China’s overseas farmland investment projects in countries along the “Belt and Road” project through spatial analysis and the Logit model. The results show that North America has the largest share of production versus contracted acreage in current acreage investment cases, and Asian projects have the highest success rate. Both successful and failed projects in China regarding arable land investment are highly correlated spatially and characterized by a strong concentration and low uniformity of distribution, with differences in the degree of concentration in Asia, Africa and other regions. The contracted area, host country participation and host country resource endowment, business environment and institutional quality have significant, inverted “U-shaped”, negative and positive effects on project success, respectively. In addition, the involvement of the host country has a significant negative impact on the success of investment projects in Africa, and the length of investment and the type of investment purpose have a significant positive and negative impact on the success of investment projects in Asian countries. Therefore, China’s overseas arable land investment should be based on a full examination of existing investment projects in each country, the selection of host countries with abundant resource endowments and a good business environment and institutional environment and the adoption of a model suitable for each location to carry out investments according to local conditions

Locally Differentially Private Heterogeneous Graph Aggregation with Utility Optimization

Graph data are widely collected and exploited by organizations, providing convenient services from policy formation and market decisions to medical care and social interactions. Yet, recent exposures of private data abuses have caused huge financial and reputational costs to both organizations and their users, enabling designing efficient privacy protection mechanisms a top priority. Local differential privacy (LDP) is an emerging privacy preservation standard and has been studied in various fields, including graph data aggregation. However, existing research studies of graph aggregation with LDP mainly provide single edge privacy for pure graph, leaving heterogeneous graph data aggregation with stronger privacy as an open challenge. In this paper, we take a step toward simultaneously collecting mixed attributed graph data while retaining intrinsic associations, with stronger local differential privacy protecting more than single edge. Specifically, we first propose a moderate granularity attributewise local differential privacy (ALDP) and formulate the problem of aggregating mixed attributed graph data as collecting two statistics under ALDP. Then we provide mechanisms to privately collect these statistics. For the categorical-attributed graph, we devise a utility-improved PrivAG mechanism, which randomizes and aggregates subsets of attribute and degree vectors. For heterogeneous graph, we present an adaptive binning scheme (ABS) to dynamically segment and simultaneously collect mixed attributed data, and extend the prior mechanism to a generalized PrivHG mechanism based on it. Finally, we practically optimize the utility of the mechanisms by reducing the computation costs and estimation errors. The effectiveness and efficiency of the mechanisms are validated through extensive experiments, and better performance is shown compared with the state-of-the-art mechanisms