ATRX is a predictive marker for endocrinotherapy and chemotherapy resistance in HER2-/HR+ breast cancer through the regulation of the AR, GLI3 and GATA2 transcriptional network.

Drug resistance in breast cancer (BC) is a clinical challenge. Exploring the mechanism and identifying a precise predictive biomarker for the drug resistance in BC is critical. Three first-line drug (paclitaxel, doxorubicin and tamoxifen) resistance datasets in BC from GEO were merged to obtain 1,461 differentially expressed genes for weighted correlation network analysis, resulting in identifying ATRX as the hub gene. ATRX is a chromatin remodelling protein, therefore, ATRX-associated transcription factors were explored, thereby identifying the network of AR, GLI3 and GATA2. GO and KEGG analyses revealed immunity, transcriptional regulation and endocrinotherapy/chemotherapy resistance were enriched. Moreover, CIBERSORT revealed immunity regulation was inhibited in the resistance group. ssGSEA showed a significantly lower immune status in the ATRX-Low group compared to the ATRX-High group. Furthermore, the peaks of H3K9me3 ChIP-seq on the four genes were higher in normal tissues than in BC tissues. Notably, the frequency of ATRX mutation was higher than BRCA in BC. Moreover, depressed ATRX revealed worse overall survival and disease-free survival in the human epidermal growth factor receptor 2 (HER2)-/hormone receptor (HR)+ BC. Additionally, depressed ATRX predicted poor results for patients who underwent endocrinotherapy or chemotherapy in the HER2-/HR+ BC subgroup. A nomogram based on ATRX, TILs and ER exhibited a significantly accurate survival prediction ability. Importantly, overexpression of ATRX significantly inhibited the IC50 of the three first-line drugs on MCF-7 cell. Thus, ATRX is an efficient predictive biomarker for endocrinotherapy and chemotherapy resistance in HER2-/HR+ BC and acts by suppressing the AR, GLI3 and GATA2 transcriptional network.

Towards sustainable transport: quantifying and mitigating pollutant emissions from heavy-duty diesel trucks in Northeast China.

Heavy-duty diesel trucks (HDDTs) have caused serious environmental pollution in China. Accurate estimation of their pollutant emission characteristics is essential to reduce emissions and associated environmental and public health impacts. To achieve sustainable development for transport emissions in Northeast China, we developed localized emission factors and a high-resolution emission inventory of HDDTs, based on on-board test, Guidebook and international vehicle emission (IVE) model. The results show that the total emissions of CO, NO, NO2, and PM from HDDTs in Northeast China in 2020 were 172.2 kt, 531.5 kt, 11.2 kt, and 921.4 t, respectively. In terms of spatial distribution, emissions decreased from the city center to the city fringe. Temporally, the NOx emission variation curves of different types of roads presented a "single-peak" emission characteristic, which was different from the peak of traffic flow. Three emission reduction scenarios are further developed in the paper. Scenario analysis shows that elimination of HDDTs that follow the old China III emission standard and installing tailpipe treatment devices are the most effective pollutant reduction measure. The reduction percentages for CO, NO, NO2, and PM ranged from 62.9 to 83.89%. The results of our study could inform policymakers to devise feasible strategies to reduce vehicle pollution in Northeast China.

Study on preparation and sintering properties of nano-silver-coated tin slurry.

A nano-sized silver-coated tin (Sn@Ag) slurry was prepared by heterogeneous flocculation method by adjusting the pH value of solution and selecting different dispersants. The slurry improved the oxidation resistance of tin and its dispersibility in silver matrix. The sintering strength of nanometre Sn@Ag slurry increases with the increase of Sn content. When the Sn content reaches 5%, the shear strength of the joint reaches the highest 50 MPa, which is more than 10 MPa higher than that of the pure nanometre silver slurry sintered joint. The increase of shear strength is due to the fact that the equilibrium phase formed after sintering is Ag-Sn replacement solid solution and intermetallic compound Ag3Sn, which have the effect of replacement solution strengthening and dispersion strengthening, respectively. It is proved by experiments and analysis that the application of nano-silver paste in chip interconnection is feasible. The research of this subject provides experimental reference and theoretical basis for the application of new generation interconnect materials in power devices and promotes the development of microelectronics packaging technology.

Simulation Palynologists for Pollinosis Prevention: A Progressive Learning of Pollen Localization and Classification for Whole Slide Images.

Existing API approaches usually independently leverage detection or classification models to distinguish allergic pollens from Whole Slide Images (WSIs). However, palynologists tend to identify pollen grains in a progressive learning manner instead of the above one-stage straightforward way. They generally focus on two pivotal problems during pollen identification. (1) Localization: where are the pollen grains located? (2) Classification: which categories do these pollen grains belong to? To perfectly mimic the manual observation process of the palynologists, we propose a progressive method integrating pollen localization and classification to achieve allergic pollen identification from WSIs. Specifically, data preprocessing is first used to cut WSIs into specific patches and filter out blank background patches. Subsequently, we present the multi-scale detection model to locate coarse-grained pollen regions (targeting at "pollen localization problem") and the multi-classifiers combination to determine the fine-grained category of allergic pollens (targeting at "pollen classification problem"). Extensive experimental results have demonstrated the feasibility and effectiveness of our proposed method.

Ultrafast pulse wave velocity and ensemble learning to predict atherosclerosis risk.

Pulse wave velocity (PWV) can evaluate potential atherosclerosis (AS) and ultrafast pulse wave velocity (ufPWV) is a new technique to accurately assess PWV. However, few studies have examined the predictive value of ufPWV for AS risk. We aimed to establish a classification model for AS risk diagnosis based on ufPWV, so that AS can be diagnosed and prevented in advance. We collected imaging data, as well as clinical and laboratory data. A total of 613 patients with 20 attributes were admitted in this study. There were 392 patients with hyperlipidemia (AS risk group) and 221 healthy adults as the control group. In order to build AS risk prediction models, we considered decision tree, five different ensemble learning (EL) models [random forest (RF), adaptive boosting (AdaBoost), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost) and light gradient boosting machine (LGBM)] and two different feature selection methods [statistical analysis and RF]. Accuracy and the area under the ROC curve (AUC) were used as the main criterion for model evaluation. In the prediction of AS risk with statistical analysis as the feature selection method, the performances of XGBoost (accuracy: 0.851; AUC: 0.884) and RF (accuracy: 0.844; AUC: 0.889) were better than other models. Besides, in the prediction of AS risk with RF as the feature selection method, the performances of LGBM (accuracy: 0.870; AUC: 0.903) and XGBoost (accuracy: 0.857; AUC: 0.903) were better than other models. In conclusions, EL models with RF as the feature selection method might provide accurate results in predicting AS risk. Besides, ufPWV, especially PWV of left common carotid artery at the end of systole, was an important feature in the AS risk prediction models.

Logistic Regression Model Based on Ultrafast Pulse Wave Velocity and Different Feature Selection Methods to Predict the Risk of Hypertension.

Background: Hypertension is the main reason why the incidence of cardiovascular disease has increased year-by-year and early diagnosis of hypertension is necessary to reducing the incidence of cardiovascular disease. This also puts forward higher requirements for the accuracy of diagnosis. We tried a variety of feature selection methods to improve the accuracy of logistic regression (LR). Methods: We collected 397 samples from Nanjing, Jiangsu, China between Jan 2016 and Dec 2017, including 178 hypertension samples and 219 control samples. It includes not only clinical and laboratory data, but also imaging data. We focused on the difference of imaging attributes between the control group and the hypertension group, and analyzed the correlation coefficients of all attributes. In order to establish the optimal LR model, this study tried three different feature selection methods, including statistical analysis, random forest (RF) and extreme gradient boosting (XGBoost). The area under the ROC curve (AUC) and accuracy were used as the main criterion for model evaluation. Results: In the prediction of hypertension, the performance of LR with RF as the feature selection method (accuracy: 0.910; AUC: 0.924) was better than the performance of LR with XGBoost as the feature selection method (accuracy: 0.897; AUC: 0.915) and the performance of LR with statistical analysis as the feature selection method (accuracy: 0.872; AUC: 0.926). Conclusion: LR with RF as the feature selection method may provide accurate results in predicting hypertension. Carotid intima-media thickness (cIMT) and pulse wave velocity at the end of systole (ESPWV) are two key imaging indicators in the prediction of hypertension.

Synthesis, Characterization, DNA/HSA Interactions, and Anticancer Activity of Two Novel Copper(II) Complexes with 4-Chloro-3-Nitrobenzoic Acid Ligand.

The purpose of this study was to identify new metal-based anticancer drugs; to this end, we synthesized two new copper(II) complexes, namely [Cu(ncba)4(phen)] (1) and [Cu(ncba)4(bpy)] (2), comprised 4-chloro-3-nitrobenzoic acid as the main ligand. The single-crystal XRD approach was employed to determine the copper(II) complex structures. Binding between these complexes and calf thymus DNA (CT-DNA) and human serum albumin (HSA) was explored by electronic absorption, fluorescence spectroscopy, and viscometry. Both complexes intercalatively bound CT-DNA and statically and spontaneously quenched DNA/HSA fluorescence. A CCK-8 assay revealed that complex 1 and complex 2 had substantial antiproliferative influences against human cancer cell lines. Moreover, complex 1 had greater antitumor efficacy than the positive control cisplatin. Flow cytometry assessment of the cell cycle demonstrated that these complexes arrested the HepG2 cell cycle and caused the accumulation of G0/G1-phase cells. The mechanism of cell death was elucidated by flow cytometry-based apoptosis assays. Western blotting revealed that both copper(II) complexes induced apoptosis by regulating the expression of the Bcl-2(Bcl-2, B cell lymphoma 2) protein family.

Riboflavin/ultraviolet A-induced collagen cross-linking in rabbit corneal scar.

AIM: To evaluate the biomechanical stability of the corneal scar treating with riboflavin and ultraviolet A (UVA). METHODS: Totally 86 New Zeal rabbits were divided into control group (group A, n=8) and trauma groups [group B (n=27), group C (n=24) and group D (n=27)]. Then groups B, C and D were divided into three sub-groups according to the time points of sacrifice, i.e. groups Ba, Ca and Da (4wk, n=8); Bb, Cb and Db (6wk, n=8); Bc (n=11), Cc (n=8) and Dc (8wk, n=11). The right corneas of these 78 rabbits in the trauma groups were penetrated. Group B were only sutured. Group C were treated with corneal cross-linking (CXL) immediately after suturing. Group D were treated with CXL seven days after suturing. The corneal scar strips of 4.0×10.0 mm2 were cut and the stress and Young's modulus at 10% strain were evaluated. Samples from the three rabbits of group Bc and three of group Dc were used to measure the expression of alpha smooth muscle action (α-SMA). RESULTS: The mechanical strength of the corneal scar increased with time, and was strongest at 8wk after the injury. The ultimate stress of corneal scar (group D) were 2.17±0.52 MPa, 2.92±0.63 MPa, and 4.21±0.68 Mpa at 4wk, 6wk and 8wk, respectively; Young's modulus were 10.94±1.57 MPa, 11.16±2.50 MPa, and 13.36±2.10 Mpa, which were higher than that of other groups except for normal control. The expression of α-SMA in group B and group D were 0.28±0.11 and 0.65±0.20, respectively, and the difference was statistically significant (P=0.048). CONCLUSION: CXL with riboflavin/UVA at seven days after suturing improved the biomechanical properties of corneal scars most effectively in the present study.

Voltammetric aptasensor for sulfadimethoxine using a nanohybrid composed of multifunctional fullerene, reduced graphene oxide and Pt@Au nanoparticles, and based on direct electron transfer to the active site of glucose oxidase.

This work describes a voltammetric and ultrasensitive aptasensor for sulfadimethoxine (SDM). It is based on signal amplification by making use of a multifunctional fullerene-doped reduced graphene oxide nanohybrid. The nanohybrid was coated with poly(diallyldimethylammonium chloride) to obtain a material (P-C60-rGO) with large specific surface area and a unique adsorption ability for loading it with glucose oxidase (GOx). The coating also facilitates the direct electron transfer between the active site of GOx and the glassy carbon electrode (GCE). The P-C60-rGO were then modified with Pt@Au nanoparticles, and the thiolated SDM-binding aptamer was immobilized on the nanoparticles. On exposure of the modified GCE to a solution containing SDM, it binds to the aptamer. The results were recorded through the signal responses generated from the redox center of GOx (FAD/FADH2) by cyclic voltammetry at a scan rate of 100 mV·s-1 from -0.25 to -0.65 V. Accordingly, The sensor has good specificity and stability, and response is linear in the 10 fg·mL-1 to 50 ng·mL-1 SDM concentration range with a detection limit of 8.7 fg·mL-1. Graphical abstract Schematic presentation of an electrochemical aptasensor for sulfadimethoxine (SDM) using multifunctional fullerene-doped graphene (C60-rGO) nanohybrids for amplification. The limit of detection for SDM is as low as 8.7 fg·mL-1.

[Application Value of Blunt Separation Method in the Modified Sytinger Technology PICC Catheterization in Hemopathic Patients].

OBJECTIVE: To explore the application value of blunt separation method in the modified sytinger technology peripherally inserted central catheter (PICC) catheterization in the hemopathic patients. METHODS: One hundred and twenty cases of the hemopathic diseases used modified sytinger technology PICC catheterization were selected from January 2016 to July 2017 in our Hospital, and randomly divided into blunt and routine group, each with 60 patients. For the routine group, the routine longitudinal method was used to expand the skin, for the blunt group the blunt separation method was used to expand the skin. RESULTS: At the time point of 24 h after the blunt catheterization, the bleeding volume and exudation rate in the blunt group were significantly lower than those in the rouline group (P<0.05). At the 1, 3, 5 d after catheterization, pain visual analogue score (VAS) showed that the scores of blunt group were significantly lower than those of the routine group (P<0.05). in expanding skin, the successful rate of catheterization once in blunt group and routine group were not significantly different (P>0.05). CONCLUSIONS: Compared with the longitudinal method, the blunt separation method has considerable skin expansion and sheath feeding effect on the modified sytinger technology PICC catheterization for the hemopathic patients. This method can effectively reduce the patient's catheter trauma and percolation, and is helpful to relieve the patients' pain symptoms, worthing for further clinical promotion.

An amperometric aptasensor for ultrasensitive detection of sulfadimethoxine based on exonuclease-assisted target recycling and new signal tracer for amplification.

The risks caused by veterinary drug residues in animal foodstuffs are of great concern to the public. Accordingly, this work reported an amperometric aptasensor for highly sensitive detection of sulfadimethoxine (SDM). Functionalised fullerene (C60)-doped graphene (C60-rGO) nanohybrid was designed and prepared to load electroactive toluidine blue (Tb) through the π-π stacking, forming a C60-rGO-Tb nanocomposite. Furthermore, the as-prepared nanocomposite was decorated with gold nanoparticles and used for the immobilization of signal probes to form a new signal tracer, which was coupled with exonuclease-catalyzed target recycling for amplification. To construct the aptasensor, a thiolated double-stranded DNA (dsDNA) of aptamer-capture probe complex was immobilised on a gold electrode surface through strong Au-S bond. In the presence of SDM, the aptamer preferred to form an aptamer-SDM complex, which led to the dissociation of dsDNA. Then aptamer could be selectively digested by RecJf exonuclease, resulting in liberated SDM molecules to participate in the next reaction cycling and achieve signal amplification. Then, capture probes released from the cyclic processes were hybridized with the signal tracer, which could further enhance electrochemical signal responses. On the basis of cascade signal amplification strategies, the proposed aptasensor exhibited a wide linear range from 10 fg/mL to 10 ng/mL for SDM with high sensitivity, good selectivity and satisfactory stability.

DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling.

Remodeling of the extracellular matrix (ECM) in the tumor microenvironment promotes glioma progression. Chondroitin sulfate (CS) proteoglycans appear in the ECM and on the cell surface, and can be catalyzed by dermatan sulfate epimerase to form chondroitin sulfate/dermatan sulfate (CS/DS) hybrid chains. Dermatan sulfate epimerase 1 (DSE) is overexpressed in many types of cancer, and CS/DS chains mediate several growth factor signals. However, the role of DSE in gliomas has never been explored. In the present study, we determined the expression of DSE in gliomas by consulting a public database and conducting immunohistochemistry on a tissue array. Our investigation revealed that DSE was upregulated in gliomas compared with normal brain tissue. Furthermore, high DSE expression was associated with advanced tumor grade and poor survival. We found high DSE expression in several glioblastoma cell lines, and DSE expression directly mediated DS chain formation in glioblastoma cells. Knockdown of DSE suppressed the proliferation, migration, and invasion of glioblastoma cells. In contrast, overexpression of DSE in GL261 cells enhanced these malignant phenotypes and in vivo tumor growth. Interestingly, we found that DSE selectively regulated heparin-binding EGF-like growth factor (HB-EGF)-induced signaling in glioblastoma cells. Inhibiting epidermal growth factor receptor (EGFR) and ErbB2 with afatinib suppressed DSE-enhanced malignant phenotypes, establishing the critical role of the ErbB pathway in regulating the effects of DSE expression. This evidence indicates that upregulation of DSE in gliomas contributes to malignant behavior in cancer cells. We provide novel insight into the significance of DS chains in ErbB signaling and glioma pathogenesis.

High-resolution 133Cs 6S-6D, 6S-8S two-photon spectroscopy using an intracavity scheme.

This Letter presents an intracavity scheme for diode laser based two-photon spectroscopy. To demonstrate generality, three (133)Cs hyperfine transition groups of different wavelengths are shown. For the 6S-6D transitions, we achieved a 10(2) times better signal-to-noise ratio than in previous work [J. Phys. Soc. Jpn. 74, 2487 (2005)] with 10(-3) times less laser power, revealing some previously vague and unobserved spectra. Possible mutual influences between the two-photon absorber and laser cavity were investigated for the first time to our knowledge, which leads to the application of a reliable hand-sized optical frequency reference. Our approach is applicable for most of the two-photon spectroscopy of alkali atoms.

Poly[[cobalt(II)-di-mu3-3,5-diaminobenzoato-kappa3N:N':O] monohydrate].

In the title compound, {[Co(C7H7N2O2)2].H2O}n, the CoII atom lies on an inversion centre and has octahedral geometry, defined by two O atoms in axial positions and four N atoms in equatorial sites from six different 3,5-diaminobenzoate ligands. Each 3,5-diaminobenzoate anion acts as a mu3-bridging ligand, linking three adjacent CoII ions through one O atom and two N atoms to form a three-dimensional coordination polymer.