Molecular classification of hormone receptor-positive HER2-negative breast cancer.

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. Accurate molecular classification is urgently required for guiding precision treatment. We established a large-scale multi-omics cohort of 579 patients with HR+/HER2- breast cancer and identified the following four molecular subtypes: canonical luminal, immunogenic, proliferative and receptor tyrosine kinase (RTK)-driven. Tumors of these four subtypes showed distinct biological and clinical features, suggesting subtype-specific therapeutic strategies. The RTK-driven subtype was characterized by the activation of the RTK pathways and associated with poor outcomes. The immunogenic subtype had enriched immune cells and could benefit from immune checkpoint therapy. In addition, we developed convolutional neural network models to discriminate these subtypes based on digital pathology for potential clinical translation. The molecular classification provides insights into molecular heterogeneity and highlights the potential for precision treatment of HR+/HER2- breast cancer.

Generation of an integration-free induced pluripotent stem cell line (LZUSHI001-A) from an epileptic patient with DGKG mutation.

Epilepsy is a common chronic neurological disorder related to genetic factors. Base on the non-integrating episomal vector technique, a human induced pluripotent stem cell (iPSC) line, termed as LZUSHI001-A, was generated from peripheral blood mononuclear cells (PBMCs) of a 11-year-old male patient with Epilepsy, who had a heterozygous (c.2042G>A, p.R681Q) mutation in the DGKG gene. LZUSHI001-A offers a useful resource to investigate pathogenic mechanisms in epilepsy, as well as a cell-based model for drug development to treat epilepsy.

A daily activity feature extraction approach based on time series of sensor events.

Activity recognition benefits the lives of residents in a smart home on a daily basis. One of the aims of this technology is to achieve good performance in activity recognition. The extraction and selection of the daily activity feature have a significant effect on this performance. However, commonly used extraction of daily activity features have limited the performance of daily activity recognition. Based on the nature of the time series of sensor events caused by daily activities, this paper presents a novel extraction approach for daily activity feature. First, time tuples are extracted from sensor events to form a time series. Subsequently, several common statistic formulas are proposed to form the space of daily activity features. Finally, a feature selection algorithm is employed to generate final daily activity features. To evaluate the proposed approach, two distinct datasets are adopted for activity recognition based on four different classifiers. The results of the experiment reveal that the proposed approach is an improvement over the commonly used approach.

Insulin receptor substrate-1 inhibits high-fat diet-induced obesity by browning of white adipose tissue through miR-503.

Genetic variation of insulin receptor substrate 1 (IRS-1) was found to modulate the insulin resistance of adipose tissues, but the underlying mechanism was not clear. To investigate how the IRS-1 was involved in the browning of white adipose tissue through miRNA, we identified a mutated Irs-1 (Irs-1-/- ) mice model and found that this mice had a reduced subcutaneous WAT (sWAT) and increased brown adipose tissue (BAT) in the interscapular region. So we isolated the bone marrow stromal cells and analyzed differentially expressed miRNAs and adipogenesis-related genes with miRNA arrays and PCR arrays. Irs-1-/- mice showed decreased miR-503 expression, but increased expression of its target, bone morphogenetic protein receptor type 1a (BMPR1a). Overexpression of miR-503 in preadipocytes downregulated BMPR1a and impaired adipogenic activity through the phosphotidylinositol 3-kinase (PI3K/Akt) pathway, while the inhibitor had the opposite effect. In both Irs-1-/- and cold-induced models, sWAT exhibited BAT features, and showed tissue-specific increased BMPR1a expression, PI3K expression, and Akt phosphorylation. Thus, our results showed that IRS-1 regulated brown preadipocyte differentiation and induced browning in sWAT through the miR-503-BMPR1a pathway, which played important roles in high-fat diet-induced obesity.

Photovoltaic Effect Related to Methylammonium Cation Orientation and Carrier Transport Properties in High-Performance Perovskite Solar Cells.

Solar cells based on organic-inorganic hybrid halide perovskites (OIHHPs) have been widely studied because of their increasing power conversion efficiency. Extensive research has been conducted in electrical and optical properties and device fabrication. However, in terms of material science, the photovoltaic effects of OIHHP are still not well understood. Here, we theoretically investigate the photovoltaic phenomena of MAPbI3 (MA = CH3NH3+) under standard AM 1.5G sunlight illumination, considering the MA cation orientation, light incident angle, polarization, and photon energy, using Keldysh nonequilibrium Green's function formalism combined with density functional theory calculations. It is found that the short-circuit current density Jsc has a maximum value of 383.149 A/m2 when the MA orientation is parallel to the transport direction, whereas it is negligible when the MA orientation is orthogonal to the transport direction. In addition, full consideration is also given to the direction of incidence of sunlight and its polarization state. Nevertheless, of all factors considered, MA orientation plays the decisive role, for Jsc still has a respectable value of 364.112 A/m2 even for a 90° sunlight incident angle relative to the transport direction, so long as the MAs are aligned in the transport direction. The increase in the photocurrent is attributed to an increase in the transmission coefficient of low-energy holes, as well as improvement of the velocities and mobilities of electrons and holes in the MAPbI3-based device with [001] MA orientation. The results suggest that during the designing of high-performance OIHHP-based solar cells and photoelectronic devices, the crystal orientation and MA cation orientation relative to the transport direction should be carefully considered as they directly affect carrier transport properties.

Influential factors for visit time for tracheobronchial foreign bodies in pediatrics.

PURPOSE: This study aims to investigate the inflential factors for visit time for tracheobronchial foreign bodies in pediatrics, and to shorten the time of diagnosis and reduce complications. METHODS: A questionnaire survey was designed and conducted among the caretakers of children with tracheobronchial foreign bodies, and the related inflential factors for visit time were analyzed. RESULTS: The visit time for tracheobronchial foreign body was correlated with the age of the child, the type of foreign body, the educational level of the caretaker, a history of foreign body aspiration were provided, an examination was performed during the visit, the anti-inflammatory and anti-allergic treatment, and transfer to a higher level hospital. Age, history of foreign body aspiration were provided, and anti-inflammatory and anti-allergic treatment were the independent inflential factors for the time of diagnosis (P < 0.05). CONCLUSION: The visit time for tracheobronchial foreign bodies was affected by many factors. It is necessary to strengthen the publicity scope and intensity on health education for tracheobronchial foreign bodies in community doctors and parents, to shorten the time of diagnosis and reduce complications.

Graphene oxide-highly anisotropic noble metal hybrid systems for intensified surface enhanced Raman scattering and direct capture and sensitive discrimination in PCBs monitoring.

Graphene oxide (GO)-anisotropic noble metal hybrid systems were developed as highly sensitive and reproducible surface enhanced Raman scattering (SERS) platform, in which ultrathin GO was embedded between two metallic layers of flower-like Ag nanoparticles (AgNFs) and gold nanostars (AuNSts). Due to multi-dimensional plasmonic coupling effect, the well-designed AgNFs-GO-AuNSts sandwich structures possessed ultrahigh sensitivity with the detection limit of R6G as low as 1.0 × 10-13 M and high enhancement factor of 2.59 × 107. Additionally, the GO interlayer could function as protective shell to suppress the oxidation of bottom silver layer and efficiently position the target analytes within hot spots. These features endow the substrate with high stability and excellent reproducibility (Signal variations < 7%). Particularly, the GO sandwiched substrate can be explored for the direct capture and sensitive detection of polychlorinated biphenyls (PCBs) without any organic modifier as molecule harvester. This minimum detected concentration was estimated as low as 3.4 × 10-6 M. The detection method based on GO mediated sandwich substrate avoids complicated surface modification manipulations and improves the substrate cleanness. Moreover, the resultant sandwich substrates can be used to recognize fingerprint peaks of different PCBs in their complex mixture, revealing great potential applications in SERS-based simultaneous detection of multiple pollutants with low affinity.

Synthesis and Electrochemical Performance of Molybdenum Disulfide-Reduced Graphene Oxide-Polyaniline Ternary Composites for Supercapacitors.

Molybdenum disulfide/reduced graphene oxide/polyaniline ternary composites (MoS2/rGO/PANI) were designed and synthesized by a facile two-step approach including hydrothermal and in situ polymerization process. The MoS2/rGO/PANI composites presented an interconnected 3D network architecture, in which PANI uniformly coated the outer surface of the MoS2/rGO binary composite. The MoS2/rGO/PANI composites with a weight percent of 80% (MGP-80) exhibits the best specific capacitance (570 F g-1 at 1 A g-1) and cycling stabilities (78.6% retained capacitance after 500 cycles at 1 A g-1). The excellent electrochemical capacitive performance is attributed to its 3D network structure and the synergistic effects among the three components that make the composites obtain both pseudocapacitance and double-layer capacitance.

Enhanced Specific Capacitance of Few-Layer MoS2 Nanosheets via SDBS-Assisted Hydrothermal Method.

Few-layer MoS2 nanosheets have been successfully synthesized by a facile anionic surfactantassisted hydrothermal approach. The as-prepared samples are characterized by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It is found that the anionic surfactant sodium dodecylbenzene sulfonate (SDBS) plays a crucial role in the formation of MoS2 nanosheets with few layers and rich exposed edges. The electrochemical performances of the as-prepared samples are evaluated by cyclic voltammogram, galvanostatic charge-discharge and electrochemical impedance spectroscopy. Compared with the pristine MoS2 without SDBS, the MoS2 nanosheets show a high specific capacitance of 223 F g-1 and its capacitance can still maintained a stable specific capacitance of 147 F g-1 after 500 cycles at 1 A g-1. The enhancement in supercapacitors is attributed to few-layer structure and exposed active edges, which enables fast electron transportation between the electrode and electrolytes. Therefore, the MoS2 nanosheets will be a suitable candidate for electrochemical supercapacitor applications.

[The X-Ray Fluorescence Spectrometer Based on Pyroelectric Effect].

Pyroelectric X-ray generator is implemented, and an X-ray fluorescence spectrometer is accomplished by combining the pyroelectric X-ray generator with a high energy resolution silicon drift detector. Firstly, the parameters of the X-ray generator are decided by analyzing and calculating the influence of the thickness of the pyroelectriccrystal and the thickness of the target on emitted X-ray. Secondly, the emitted X-ray is measured. The energy of emitted X-ray is from 1 to 27 keV, containing the characteristic X-ray of Cu and Ta, and the max counting rate is more than 3 000 per second. The measurement also proves that the detector of the spectrometer has a high energy resolution which the FWMH is 210 eV at 8. 05 keV. Lastly, samples of Fe, Ti, Cr and high-Ti basalt are analyzed using the spectrometer, and the results are agreed with the elements of the samples. It shows that the spectrometer consisting of a pyroelectric X-ray generator and a silicon drift detector is effective for element analysis. Additionally, because each part of the spectrometer has a small volume, it can be easily modified to a portable one which is suitable for non-destructive, on-site and quick element analysis.

Dose-dependent effects of neuropeptide Y on the regulation of preadipocyte proliferation and adipocyte lipid synthesis via the PPARγ pathways.

The objective of this study was to investigate the impact of neuropeptide Y (NPY) on preadipocyte proliferation and differentiation. Preadipocytes were incubated with a range of concentrations of NPY (10(-15)M - 10(-7)M). After NPY-induced differentiation, the extent of preadipocyte adipogenesis was evaluated. The expressions levels of related adipocyte markers such as PPARγ, C/EBPα and DLK-1 were examined by real-time PCR (RT-PCR) or western blot analysis. Furthermore, the mitogen-activated protein kinase (MAPK) signaling pathway proteins were also analyzed by western blot. Our results showed that low doses of NPY stimulated preadipocyte viability and proliferation, while high NPY doses inhibited cell viability. At high concentrations of NPY significantly promoted lipid accumulation and increased the size of lipid droplets. DLK-1 mRNA expression was inhibited, but the expression levels of PPARγ and C/EBPα were increased during differentiation with the presence of high concentration of NPY. High-dose NPY also suppressed the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2 protein. We conclude that NPY has a biphasic effect on preadipocyte proliferation. A high dose inhibits the proliferation of 3T3-L1 cell while promotes adipocyte differentiation, increasing lipid accumulation especially enlarged lipid droplets' size. NPY may lead to a better understanding for drug development to prevent hyperplastic obesity and hypertrophic obesity.

[Near infrared distance sensing method for Chang'e-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover, the scientific objective of which is in-situ observation and off-line analysis of lunar regolith and rock. Distance measurement is one of the important functions for APXS to perform effective detection on the moon. The present paper will first give a brief introduction to APXS, and then analyze the specific requirements and constraints to realize distance measurement, at last present a new near infrared distance sensing algorithm by using the inflection point of response curve. The theoretical analysis and the experiment results verify the feasibility of this algorithm. Although the theoretical analysis shows that this method is not sensitive to the operating temperature and reflectance of the lunar surface, the solar infrared radiant intensity may make photosensor saturation. The solutions are reducing the gain of device and avoiding direct exposure to sun light.

Dysfunction of collagen synthesis and secretion in chondrocytes induced by wisp3 mutation.

Wisp3 gene mutation was shown to cause spondyloepiphyseal dysplasia tarda with progressive arthropathy (SRDT-PA), but the underlying mechanism is not clear. To clarify this mechanism, we constructed the wild and mutated Wisp3 expression vectors and transfected into human chondrocytes lines C-20/A4; Wisp3 proteins subcellular localization, cell proliferation, cell apoptosis, and Wisp3-mediated gene expression were determined, and dynamic secretion of collagen in transfected chondrocytes was analyzed by (14)C-proline incorporation experiment. Mutated Wisp3 protein increased proliferation activity, decreased apoptosis of C-20/A4 cells, and aggregated abnormally in cytoplasm. Expression of collagen II was also downregulated in C-20/A4 cells transfected with mutated Wisp3. Wild type Wisp3 transfection increased intracellular collagen content and extracellular collagen secretion, but the mutated Wisp3 lost this function, and the peak phase of collagen secretion was delayed in mutated Wisp3 transfected cells. Thus abnormal protein distribution, cell proliferation, collagen synthesis, and secretion in Wisp3 mutated chondrocytes might contribute to the pathogenesis of SEDT-PA.

Alpha-tocopheryl polyethylene glycol succinate-emulsified poly(lactic-co-glycolic acid) nanoparticles for reversal of multidrug resistance in vitro.

Multidrug resistance (MDR) is one of the factors in the failure of anticancer chemotherapy. In order to enhance the anticancer effect of P-glycoprotein (P-gp) substrates, inhibition of the P-gp efflux pump on MDR cells is a good tactic. We designed novel multifunctional drug-loaded alpha-tocopheryl polyethylene glycol succinate (TPGS)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPGS/PLGA/SN-38 NPs; SN-38 is 7-ethyl-10-hydroxy-camptothecin), with TPGS-emulsified PLGA NPs as the carrier and modulator of the P-gp efflux pump and SN-38 as the model drug. TPGS/PLGA/SN-38 NPs were prepared using a modified solvent extraction/evaporation method. Physicochemical characterizations of TPGS/PLGA/SN-38 NPs were in conformity with the principle of nano-drug delivery systems (nDDSs), including a diameter of about 200 nm, excellent spherical particles with a smooth surface, narrow size distribution, appropriate surface charge, and successful drug-loading into the NPs. The cytotoxicity of TPGS/PLGA/SN-38 NPs to MDR cells was increased by 3.56 times compared with that of free SN-38. Based on an intracellular accumulation study relative to the time-dependent uptake and efflux inhibition, we suggest novel mechanisms of MDR reversal of TPGS/PLGA NPs. Firstly, TPGS/PLGA/SN-38 NPs improved the uptake of the loaded drug by clathrin-mediated endocytosis in the form of unbroken NPs. Simultaneously, intracellular NPs escaped the recognition of P-gp by MDR cells. After SN-38 was released from TPGS/PLGA/SN-38 NPs in MDR cells, TPGS or/and PLGA may modulate the efflux microenvironment of the P-gp pump, such as mitochondria and the P-gp domain with an ATP-binding site. Finally, the controlled-release drug entered the nucleus of the MDR cell to induce cytotoxicity. The present study showed that TPGS-emulsified PLGA NPs could be functional carriers in nDDS for anticancer drugs that are also P-gp substrates. More importantly, to enhance the therapeutic effect of P-gp substrates, this work might provide a new insight into the design of pharmacologically inactive excipients that can serve as P-gp modulators instead of drugs that are P-gp inhibitors.

[Temperature effect correction for Chang'E-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover of China's Lunar Exploration Project. The present paper introduces briefly the components of APXS, how it works and its working environment on the lunar surface. The environmental temperature effect has been studied with simulations and experiments, and the results show that the temperature of the APXS sensor will be varying during the measuring on the lunar surface. And another experiment reveals that the energy resolution becomes worse if the sensor's temperature is varying. In this paper, a correction method based on Pearson's chi-squared test is presented. The method can improve the energy resolution when the sensor's temperature is varying. We have tested the method with the spectra acquired by APXS in the temperature varying period of Temperature Cycling Test, and the results show that the method is efficient and reliable.

(E)-1-Phenyl-3-[4-(trifluoro-meth-yl)phen-yl]prop-2-en-1-one.

In the title compound, C(16)H(11)F(3)O, the dihedral angle between the two rings is 48.8 (2)°. The crystal packing exhibits no classical inter-molecular inter-actions between the mol-ecules.

Di-µ-aqua-bis-{diaqua-[µ-4-({4-[bis-(2-hy-droxy-eth-yl)amino]-6-chloro-1,3,5-triazin-2-yl}amino)-benzene-sulfonato]-sodium(I)}.

In the dinuclear title compound, [Na(2)(C(13)H(15)ClN(5)O(5)S)(2)(H(2)O)(6)](n), two Na(+) cations, disposed about a centre of inversion, are linked by two bridging water mol-ecules. The coordination geometry is based on an O(5) donor set defined by four water mol-ecules and a 4-amino-benzene-sulfonate O atom in a distorted trigonal-bipyramidal geometry. In the crystal, significant O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds lead to the formation of a three-dimensional architecture.

3-Nitro-2-phenyl-chroman.

In the title compound, C(15)H(13)NO(3), the dihedral angle between the two aromatic rings is 79.25 (16)°.

Diphenyl-methyl isothio-cyanate.

The asymmetric unit of the title compound, C(14)H(11)NS, contains two mol-ecules in which the dihedral angles between the phenyl rings are 77.23 (7) and 86.30 (7)°. No aromatic π-π stacking inter-actions are observed.

EGF-functionalized single-walled carbon nanotubes for targeting delivery of etoposide.

To enhance the therapeutic potential of etoposide (ETO), we devised a targeted drug delivery system (TDDS) of epidermal growth factor-chitosan-carboxyl single-walled carbon nanotubes-ETO (EGF/CHI/SWNT-COOHs/ETO) using modified SWNTs (m-SWNTs) as the carrier, EGF-functionalized SWNTs (f-SWNTs) as the targeted moiety and ETO as the drug. After SWNT-COOHs were conjugated with CHI (CHI/SWNT-COOHs/ETO), they displayed high solubility and stable dispersion in aqueous solution. The drug loading capacity was approximately 25-27%. The m-SWNTs and f-SWNTs had only slight cytotoxicity. ETO was released from EGF/CHI/SWNT-COOHs/ETO at low pH and taken up by tumour cells via adenosine triphosphate (ATP)-dependent endocytosis. The cell death induced by EGF/CHI/SWNT-COOHs/ETO was as much as 2.7 times that due to ETO alone. In summary, these results demonstrated that our TDDS had a greater anticancer effect than free ETO in vitro.