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Additional file 1: Fig. S1. Up-regulation of mRNA expression of chemokine genes during aging in AD mouse models. Fig. S2. Correlation between the mRNA expression levels of chemokine genes with AD pathology in AD mouse models. Table S1. Sequence coverage of each gene in the targeted sequencing. Table S2. Results of SKAT-O analysis in Han Chinese with and without AD. Table S3. Results of gene-based burden test of chemokine genes from ADSP. Table S4. Association results of common variants in European population.

The previous study has shown that transcriptional factor MEOX1 could promote proliferation and sphere formation ability of non-small cell lung cancer (NSCLC) cells, however, we found that MEOX1 mRNA was lowly expressed in lung cancer tissues compared to that in normal adjacent tissues, and MEOX1 mRNA expression was positively correlated with the survival of lung cancer patients, especially in lung adenocarcinoma patients. Functional experiments using in vitro and in vivo experiments revealed that stable overexpression of MEOX1 significantly suppressed the proliferation ability, promoted cell cycle arrest in G2 phase, and apoptotic ability of NSCLC cells. Additionally, it was identified that MEOX1 and CCNB1 mRNA expression exhibited a negative correlation in different lung cancer tissues. Mechanistically, we indicated that MEOX1 bound to the transcriptional initiation site of CCNB1 and thus suppressed CCNB1 expression. Notably, CCNB1 overexpression rescued the inhibition of MEOX1 overexpression on NSCLC progression. This study deciphers a novel MEOX1/CCNB1 axis suppressing NSCLC progression.

With the continuous advancement of low-altitude UAV (unmanned air vehicle, UAV) technology for the earth observation and its wide popularity, UAV photogrammetry and SfM (Structure from Motion, SfM) methods have received more and more attention as the latest means to obtain true 3D realistic models of the survey area. As the newest means of measuring geomorphological information, UAV low-altitude photogrammetry and SfM methods can quickly obtain a true 3D realistic model of the survey area, and have been applied to a number of research fields. In this paper, the UAV is used to measure the typical local scene of annular landform at the southern edge of Dinosaur Valley in Lufeng, and the high-resolution geomorphological image data of the investigated area are obtained. Combined with the SFM method, a realistic 3D scene model is constructed, and its geomorphological characteristics are discussed and analyzed. The experimental results show that the DSM (digital surface model, DSM) data based on the SFM method can obtain ground points by filtering, diluting, and classifying the data, and the DEM (digital elevation model, DEM) data with a resolution of 0.2m is constructed by using the progressive encrypted triangular mesh method, which can accurately represent the true geomorphological characteristics of the study area. (2) Construction of three typical elevation profiles of the circular scene “inner-middle-outer,” and comparative analysis of the profiles confirmed that the topography of the study area is characterized by the dome ridge line AA' as the main highland ridge line, showing a circular “basin margin” pattern, with gradually decreasing elevations on the inner and outer sides. (3) In order to reveal the complex tectonic geomorphological features of the external scene between the ridge and trough, the ArcGIS surface analysis method was used to extract the ridge lines J1-J7. Accurate quantitative measurements and analysis were carried out to investigate the slope, slope length, slope direction, ridge area face, and other related parameters. (4) Using the multi-view visual interpretation and typical scene analysis of the three-dimensional 3D model, micro-geomorphological features such as the development of washouts in the survey area and the nodal laminar surface of the geological body can be clearly identified. In addition, the coordinates of the geological body’s spatial location and its production, spreading area, square volume, and other rich geological information can be accurately obtained. Through the above experimental study on the detection of 3D scenes of landforms, the advantages of UAV measurement technology and SFM method to construct DSM data and 3D scene models in fine geological structure detection are demonstrated. This will have an important application prospect and practical value for geological survey, monitoring , prevention and control management in mountainous areas .In addition, the fast, low-cost, high-precision, and non-contact measurement mode can provide accurate data basis and technical support for geological structure detection, geological disaster investigation, risk assessment and prevention and control management.

With the rapid development of AC-DC hybrid microgrid and the widespread application of power electric components, AC-DC hybrid park micro-grid based on the topology of electric energy router application(EERA) emerged. In this paper, the matching of the DC/AC devices and DC/DC devices capacity in the planning stage be optimized based on the port model of the electric energy router application. At the same time, the economic operation of the park microgrid is realized by quantifying the life loss cost of energy storage. Therefore, a bi-level optimization model that takes into account both the economic operation of the park microgrid and the investment of PV-energy storage combined power generation system containing the electric energy routers application is proposed. Given the different characteristics of the operating variables and planning variables, the optimization target is solved by the method of combining improved particle swarm algorithm using the Shannon information entropy model and mixed-integer quadratic programming (MIQP) based on the ideas of hierarchical decoupling. Through simulation calculation in different scenarios, it is verified that the effectiveness of the model and the feasibility of the algorithm. Finally, this model can provide a certain reference for the configuration of the park microgrid capacity based on the electric energy router application.

The nonlinear characteristics of wind power series and random fluctuation characteristics of wind resources have a harmful effect on stability of wind power prediction. This paper proposes a novel hybrid wind power short-term prediction model for improving precision and stability of wind power prediction. Firstly, the non-stationary wind power time series is decomposed by complete ensemble empirical mode decomposition - Lempel-Ziv complexity (CEEMD-LZC). Secondly, local linear embedding (LLE) is used to reduce the dimension of meteorological data with maintaining the essential structure of meteorological data. The integrated meteorological data predigested by LLE are treated as input of the prediction model. Finally, ant lion optimization (ALO) is utilized to optimize the weights and biases of extreme learning machine (ELM) network nodes to improve ELM prediction performance. The results of case studies show that the proposed model has a good forecasting effect and is more advantageous in 48h-ahead wind power forecasting.

Cytochrome P450 monooxygenases (P450s) and UDP-glycosyltransferases (UGTs) are major detoxifying enzymes that metabolize plant toxins and insecticides. In the present study, the synergists of piperonyl butoxide, sulfinpyrazone and 5-nitrouracil significantly increased cyantraniliprole and α-cypermethrin toxicity against the resistant strain. The transcripts of UGT341A4, UGT344B4, UGT344D6, UGT344J2 and UGT344M2 increased significantly in the CyR strain compared with the susceptible strain. Among these upregulated genes (including P450s), CYP6CY7 and UGT344B4 were highly expressed in the midgut. Transgenic expression of the P450 and UGT genes in broad body tissues in Drosophila melanogaster indicated that the expression of CYP380C6, CYP4CJ1, UGT341A4, UGT344B4 and UGT344M2 is sufficient to confer cyantraniliprole resistance, and CYP380C6, CYP6CY7, CYP6CY21, UGT341A4 and UGT344M2 are related to α-cypermethrin cross-resistance. The midgut-specific overexpression of CYP380C6, CYP6CY7, CYP6CY21, CYP4CJ1, UGT341A4, UGT344B4 and UGT344M2 significantly increased insensitivity to cyantraniliprole, and CYP380C6, CYP6CY7, CYP6CY21, UGT344B4 and UGT344M2 confer α-cypermethrin cross-resistance. The expression of CYP380C6, CYP4CJ1, UGT341A4 and UGT344M2 in broad tissues or in midgut has similar effects on insensitivity to insecticides; however, CYP6CY7, CYP6CY21 and UGT344B4 are more effective in the midgut. This result indicates that broad body tissues and midgut tissue are involved in insecticide resistance mediated by the candidate P450s and UGTs examined.

As a subjective mood-related disorder with an unclear mechanism, depression has many problems in its diagnosis, which offers great space and value for research. At present, the methods commonly used to judge whether an animal model of depression has been established are mainly by biochemical index detection and behavioral tests, both of which inevitably cause stress in animals. Stress-induced hair growth inhibition has been widely reported in humans and animals. The simplicity of collecting hair samples and the observable state of hair growth has significant advantages; we tried to explore whether the parameters related to hair growth could be used as auxiliary indicators to evaluate a depression model in animals. The length and weight of the hair were calculated. Correlation analysis was conducted between the depressive behavioral results and the glucocorticoid levels in hair and serum. Learned helplessness combined with chronic restraint stress, and chronic unpredictable stress in the animal were detectable by superficial observation, weight ratio, and length of hair, and follicular development scores were significantly reduced compared to the control. The hair growth parameters of rats with depression, the rise in corticosterone, and the corresponding changes in behavioral parameters were significantly correlated. The neurotrophic factors, glucocorticoid-receptor (GR), brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 5 (FGF5), are associated with depression and hair growth. Significant differences were detected between the stress and control groups, suggesting that the mechanism underlying the stress-phenomenon inhibition of hair growth may be related to growth factor mediation.

Lambda-cyhalothrin is now widely used in China to control the soybean aphid Aphis glycines. To dissect the resistance mechanism, a laboratory-selected resistant soybean aphid strain (CRR) was established with a 43.42-fold resistance ratio to λ-cyhalothrin than the susceptible strain (CSS) in adult aphids. In this study, a comparative proteomic analysis between the CRR and CSS strains revealed important differences between the susceptible and resistant strains of soybean aphids for λ-cyhalothrin. Approximately 493 protein spots were detected in two-dimensional polyacrylamide gel electrophoresis (2-DE). Thirty-six protein spots displayed differential expression of >2-fold in the CRR strain compared to the CSS strain. Out of these 36 protein spots, 21 had elevated and 15 had decreased expression. Twenty-four differentially expressed proteins were identified by MALDI TOF MS/MS and categorized into the functional groups cytoskeleton-related protein, carbohydrate and energy metabolism, protein folding, antioxidant system, and nucleotide and amino acid metabolism. Function analysis showed that cytoskeleton-related proteins and energy metabolism proteins have been associated with the λ-cyhalothrin resistance of A. glycines. The differential expression of λ-cyhalothrin responsive proteins reflected the overall change in cellular structure and metabolism after insecticide treatment in aphids. In summary, our studies improve understanding of the molecular mechanism resistance of soybean aphid to lambda-cyhalothrin, which will facilitate the development of rational approaches to improve the management of this pest and to improve the yield of soybean.

Non-small cell lung cancer (NSCLC) is one of the causes of cancer mortality worldwide. The role of miR-26 in the development and progression of NSCLC remains largely unknown. In this study we found an abnormal expression of miR-26 in human NSCLC tissues. It was found that miR-26 mimics induced cell apoptosis and promoted caspase-3, 9 activities in human NSCLC cells. The miR-26 inhibitor enhanced the expression of the light chain 3 (LC3) protein and the autophagy related genes in NSCLC cells. Moreover, miR-26 regulated apoptosis and autophagy by inhibiting TGF-β expression in a JNK dependent manner. In addition, miR-26 mimics induced cell apoptosis, was involved in the endoplasmic reticulum stress (ERS) signaling pathway. Down-regulation of the ERS, inhibited apoptosis which was induced by miR-26 mimics in NSCLC cells. In in vivo studies, TUNEL staining revealed that the number of TUNEL positive cells of the tumor tissue in the miR-26 treatment group, were significantly increased in comparison with the control group, while the number of TUNEL positive cells in the tumor tissue were remarkably decreased in the groups treated with miR-26, combined with the TGF-β1 inhibitor or JNK inhibitor. Additionally, the immunoreactivity of TGF-β1 in the cells treated with the miR-26 inhibitor, decreased in comparison to the control group. Our results indicated that miR-26 induced apoptosis and inhibited autophagy in human NSCLC cells through the TGF-β1-JNK signaling pathway, suggesting that miR-26 could be a potential novel target for the treatment of NSCLC.

Cotton plants accumulate phytotoxins, such as gossypol and related sesquiterpene aldehydes, to resist insect herbivores. The survival of insects exposed to toxic secondary metabolites depends on the detoxification metabolism mediated by limited groups of cytochrome P450. Gossypol has an antibiotic effect on Aphis gossypii, and as the concentrations of gossypol were increased in the present study, the mortality of cotton aphids increased from 4 to 28%. The fecundity of the cotton aphids exposed to gossypol was also significantly reduced compared with the control. The transcriptional levels of CYP6DA2 in cotton aphids were significantly induced when exposed to gossypol, and knockdown of the CYP6DA2 transcripts by RNA interference (RNAi) significantly increased the toxicity of gossypol to cotton aphids. To further understand the gossypol regulatory cascade, the 5'-flanking promoter sequences of CYP6DA2 were isolated with a genome walker, and the promoter was very active and was inducible by gossypol. Co-transfection of the cap 'n' collar isoform C (CncC) and CYP6DA2 promoters dramatically increased the expression of CYP6DA2, and suppression of the CncC transcripts by RNAi significantly decreased the expression levels of CYP6DA2, and significantly increased the toxicity of gossypol to cotton aphids. Thus, the transcriptional regulation of CYP6DA2 involved the transcriptional factor CncC.

A resistant strain of the cotton aphid (SR) developed 441.26-fold and 11.97-fold resistance to spirotetramat for adult aphids and nymphs, respectively, compared with the susceptible (SS) strain. Solexa sequencing technology was employed to identify differentially expressed genes (DEGs) in the spirotetramat-resistant cotton aphid. Respective totals of 22,430,522 and 21,317,732 clean reads were obtained from SR and SS cDNA libraries and assembled into 35,222 non-redundant (Nr) consensus sequences. A total of 14,913, 9,220, 7,922, 4,314 and 4,686 sequences were annotated using Nr, Swiss-Prot, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG), respectively. Compared with the SS strain, the SR strain had 1287 significantly changed unigenes, of which 130 genes were up-regulated and 1157 genes were down-regulated (P ≤ 0.001). Among these genes, 440 unigenes were annotated, consisting of 114 up-regulated and 326 down-regulated genes. The expression levels of heat shock protein 70 (Hsp70) and UDP-glucuronosyltransferase were significantly up-regulated in the SR strain compared to the SS strain. The genes encoding cuticle proteins, salivary glue protein, fibroin heavy chain, energy ATP synthase, and cytochrome c oxidase were dramatically decreased. Among the DEGs, cytochrome P450 6A2 (c20965.graph_c0) was the only P450 gene up-regulated in the SR strain. The expression levels of 10 DEGs were confirmed by real-time qPCR, and the trends in gene expression observed by qPCR matched those of the Solexa expression profiles. The acetyl-CoA carboxylase (ACC) genes in the SR and SS libraries both contain four single nucleotide polymorphisms (SNPs), with three common SNPs: 1227 (C/T), 1811 (A/T: F/Y) and 3759 (C/T); however, 7540 (A/T) and 108 (G/A) occurred solely in the SS and SR strains, respectively.

Granular cell tumors (GCTs) are rare tumors that can arise in multiple anatomical locations, and are characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs are currently unknown. Here, we apply whole-exome sequencing and targeted sequencing analysis to reveal mutually exclusive, clonal, inactivating somatic mutations in the endosomal pH regulators ATP6AP1 or ATP6AP2 in 72% of GCTs. Silencing of these genes in vitro results in impaired vesicle acidification, redistribution of endosomal compartments, and accumulation of intracytoplasmic granules, recapitulating the cardinal phenotypic characteristics of GCTs and providing a novel genotypic–phenotypic correlation. In addition, depletion of ATP6AP1 or ATP6AP2 results in the acquisition of oncogenic properties. Our results demonstrate that inactivating mutations of ATP6AP1 and ATP6AP2 are likely oncogenic drivers of GCTs and underpin the genesis of the intracytoplasmic granules that characterize them, providing a genetic link between endosomal pH regulation and tumorigenesis.

The samples of LaF3∶Sm3+, LaF3∶Eu3+ and LaF3∶Sm3+/Eu3+nanocrystals with high quality mono-disperse and uniform sizes were synthesized with hydrothermal method. The crystallographic phase, surface morphology, crystalline sizes and fluorescence properties of Sm3+/Eu3+ sole- and co-doped nanocrystals were characterized with X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and photoluminescence (PL) spectroscopic technique, respectively. The results of XRD and TEM show that the microstructure of the nanocrystals is hexagonal, with the average size about 40 nm. Using 442 nm He-Cd continuous wave (CW) laser to pump the Sm3+ ions doped in the LaF3∶Sm3+/Eu3+nanocrystals, the typical fluorescence emissions originating from the Eu3+ions were observed in the emission spectra, and that the energy transfer from Sm3+ions to Eu3+ions was completed. The mechanism and efficiency of the energy transfer from Sm3+ions to Eu3+ ions were investigated and discussed systematically based on the spectroscopic method. It is shown that the energy transfer of Sm3+→Eu3+ is attributed to the cross-relaxation between the excited state 4G5/2 of Sm3+ ion and the 5D1 and 5D0 states of Eu3+ ion. Meanwhile, the intensities of the characteristic fluorescence emissions of Eu3+ ions become stronger and stronger with the increase of the Eu3+ doping concentration, which suggest that the efficiency of energy transfer from Sm3+ ions to Eu3+ ions can be effectively improved by increasing the doping concentration of Eu3+ acceptor.

Anthraquinones constitute an important class of natural and synthetic compounds with a broad scope of pharmacological including anti-bacterial, antioxidant, laxative, anti-tumor and other activities. Physcion and physcion 8-O-β-glucopyranoside (PG) are common anthraquinones existed in various plants. Emerging studies suggested that physcion and PG not only exert anti-tumor, anti-microbial, anti-inflammatory, anti-oxidant, optical-related, enzyme inhibitory, lipid regulation and neuroprotective activities, but also lead to hepatotoxicity, renal toxicity and genetic damage. Besides, a growing number of pharmacokinetics researches of physcion and PG also have been conducted. However, no review of physcion or PG have been published by now, so the aim of present review is to give a comprehensive summary and analysis of the pharmacology, toxicity and pharmacokinetics of physcion and PG by consulting all the currently available literatures published in PubMed then give a future prospects about it.

Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic., This work was supported in part by the Meredith Israel Thomas Fund, the Breast Cancer Research Foundation, the Sarah Jenkins Fund, a Cancer Center Support Grant from the National Institutes of Health (NIH)/National Cancer Institute (Grant No. P30CA008748), NIH grants CA192393 and CA176785, and a Sponsored Program of Research Excellence (SPORE) in Breast Cancer (P50 CA116201). GCT is supported by the National Health and Medical Research Council of Australia

Cox regression analysis of PD-L1 expression and clinicopathological factors predicting DFS. (DOCX 15Â kb)

Clinicopathological features of the three groups: PT-/LNM-, PT-/LNM+ and PT+/LNM+ (DOCX 19Â kb)

Cox regression analysis of PD-L1 expression and clinicopathological factors predicting DFS. (DOCX 15Â kb)

Cox regression analysis of PD-L1 expression and clinicopathological factors predicting OS. (DOCX 15Â kb)

Cox regression analysis of PD-L1 expression and clinicopathological factors predicting OS. (DOCX 15Â kb)

Clinicopathological features of the three groups: PT-/LNM-, PT-/LNM+ and PT+/LNM+ (DOCX 19Â kb)

A resistant strain of the Aphis glycines Matsumura (CRR) has developed 76.67-fold resistance to lambda-cyhalothrin compared with the susceptible (CSS) strain. Synergists piperonyl butoxide (PBO), S,S,S-Tributyltrithiophosphate (DEF) and triphenyl phosphate (TPP) dramatically increased the toxicity of lambda-cyhalothrin to the resistant strain. Bioassay results indicated that the CRR strain had developed high levels of cross-resistance to chlorpyrifos (11.66-fold), acephate (8.20-fold), cypermethrin (53.24-fold), esfenvalerate (13.83-fold), cyfluthrin (9.64-fold), carbofuran (14.60-fold), methomyl (9.32-fold) and bifenthrin (4.81-fold), but did not have cross-resistance to chlorfenapyr, imidacloprid, diafenthiuron, abamectin. The transcriptional levels of CYP6A2-like, CYP6A14-like and cytochrome b-c1 complex subunit 9-like increased significantly in the resistant strain than that in the susceptible. Similar trend were observed in the transcripts and DNA copy number of CarE and E4 esterase. Overall, these results demonstrate that increased esterase hydrolysis activity, combined with elevated cytochrome P450 monooxygenase detoxicatication, plays an important role in the high levels of lambda-cyhalothrin resistance and can cause cross-resistance to other insecticides in the CRR strain.

Associations of clinical parameters with hormone receptor expression in LGSC. Table S2. Univariate analyses of risk factors for OS in LGSC cases. Table S3. Univariate analyses of risk factors for OS in HGSC cases. (DOC 95 kb)

Associations of clinical parameters with hormone receptor expression in LGSC. Table S2. Univariate analyses of risk factors for OS in LGSC cases. Table S3. Univariate analyses of risk factors for OS in HGSC cases. (DOC 95 kb)

Information of antibodies used in immunohistochemistry. Table S2A. Relationship with clinicopathological factors-HGSC. Table S2B. Relationship with clinicopathological factors-CCC. Table S3 Association molecular biomarkers expression and platinum-based chemotherapeutic response. Table S4. Comparison of molecular biomarkers between recurrent and disease-free patients. (DOCX 42 kb)

This paper discusses the research and implementation of the mid-frequency power (MFP). The paper analyzes the present research situation and the existence question of 400Hz mid-frequency power supply. Then the research of full digital control realization process of mid-frequency power supply with high power factor and multiple closed-loop feedback (MCLF) is given. The principle and characteristic of the closed-loop control system are provided. Finally the experimental prototype taking DSP of TMS320F2812 type as control device is developed. The experimental results verify the rationality .

AimsGATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in breast and urothelial carcinomas. Its diagnostic utility in primary and metastatic breast cancers has been explored and confirmed. However, the relationship between GATA3 expression and different breast carcinoma intrinsic subtypes has not been specifically defined in the literature despite a few reports with a small number of cases. The aim of the current investigation is to clarify GATA3 expression among different histological subtypes and surrogate molecular breast carcinoma subtypes in a large series of cases.MethodsImmunohistochemical staining of GATA3, GCDFP15 and mammaglobin was performed in a cohort of 1637 cases of primary invasive breast carcinoma. The association of GATA3 expression with different histological and surrogate intrinsic subtypes was assessed and compared with the expression of GCDFP15 and mammaglobin.ResultsThe overall positivity of GATA3 across the various immunohistochemistry-based surrogate intrinsic subtypes was 99.51% for luminal A-like, 97.70% for luminal B-like, 68.50% for HER2 overexpression and 20.16% for triple negative breast cancers. GATA3 expression was positively correlated with estrogen receptor (ER)-positive (luminal subtypes) breast carcinomas. For luminal-like and HER2 overexpression subtypes, GATA3 was much more sensitive than GCDFP15 and mammaglobin. For triple negative tumours, GATA3 was less sensitive than GCDFP15.ConclusionsGATA3 exhibits a relatively high sensitivity for breast carcinomas. It is more sensitive than GCDFP15 and mammaglobin in luminal-like and HER2 overexpression subtypes. GATA3 expression is associated with breast carcinomas of luminal subtype and low histological grade.

The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

With the massive production of renewable energy, negative power flows occur in many areas due to the input of a high proportion of renewable power into medium- and lower-voltage systems. These negative power flows alter the traditional radiative pattern of power distribution and cause operational safety problems such as overvoltage and massive transmission losses. Exploiting the reverse flow within certain areas as well as the different outwarding power characteristics of different substations with the aim of ensuring power supply quality would reduce the need to install energy storage systems. Here, a grid partitioning method is proposed that considers the complementary characteristics as well as electrical distances of different substations. A planning model is proposed considering the potential profitability of installing renewable power generation and clustering outwarding power and transmission losses. The uncertainty of renewable power generation and load is considered using worst-case scenarios to ...

Spirotetramat were now widely used for control insecticides resistant aphids since 2011 in China. In order to elucidate the possible resistance mechanism, a laboratory selected resistant strain (SR) of cotton aphid was established with a 578.93-fold and 14.91-fold resistance ratio to spirotetramat for adult aphids and nymph, respectively, as compared with the susceptible strain (SS). In this study, a comparative proteomic analysis between SR and SS strains were conducted aims to better understand the resistant cotton aphids' spirotetramat tolerance mechanism. Approximately 493 protein spots were detected in the two-dimension polyacrylamide gel electrophoresis (2-DE). The intensities of 35 protein spots significantly changed, showing differences more than 2-fold in the SR strain compared with that in the SS strain. Of these spots, 20 protein spots were more abundant in the SR strain and 15 protein spots were more abundant in the SS strain. Twenty six differently expressed proteins were identified and categorized into several functional groups including carbohydrate and energy metabolism, antioxidant system, protein folding, amino acid metabolism, secondary metabolism and cytoskeleton protein, etc. Among these proteins, the acetyl-coA carboxylase (ACC), heat shock protein 70, ubiquitin-conjugating enzyme, fatty acid synthase, UDP-glucose 6-dehydrogenase, etc. are speculated confer the spirotetramat resistance in cotton aphids.

A thiamethoxam-resistant strain of cotton aphid (ThR) strain displayed a 19.35-fold greater resistance to thiamethoxam compared to a susceptible cotton aphid (SS) strain. Solexa sequencing technology was used to investigate differentially expressed genes (DEGs) in cotton aphids in the context of thiamethoxam resistance. A total of 22,569,311 and 21,317,732 clean reads were obtained from the ThR and SS transcriptomes, respectively, and assembled into 35,222 non-redundant (Nr) consensus sequences. The expression of 620 unigenes changed significantly in the ThR libraries compared to the SS strain; 349 genes were up-regulated, and 271 genes were down-regulated (P≤0.001). Expression levels of ribosomal proteins, ATP synthase, cytochrome c oxidase, ecdysteroid UDP-glucosyltransferase and esterase were up-regulated significantly in the ThR strain compared to the SS strain. The genes of cuticle proteins, salivary proteins, and fibroin heavy chain decreased dramatically. One nicotinic acetylcholine receptor (nAChR) α subunit was down-regulated in the ThR strain. The expression levels of 10 differentially expressed unigenes were confirmed using real-time RT-PCR, and the observed trends in gene expression matched the Solexa expression profiles. Specific single-nucleotide polymorphisms (SNPs) in nAChRs that cause amino acid substitution were found from the ThR and SS stains respectively. These data illustrate that genetic changes in nAChR genes and up-regulated ribosomal proteins, ecdysteroid UDP-glucosyltransferase, cytochrome c oxidase, esterase and peroxidase may confer the tolerance of resistant cotton aphids to thiamethoxam.

The powder samples of Sm3+/Eu3+ co-doped in LaOF nanocrystals were synthesized by using a hydrothermal-sintering technique. The characterization results of XRD and TE M suggests that t he structure of the nanocrystals is tetragonal,and its size is between 60-80 nm. Using 442 nm laser to pump the LaOF: Sm3+/Eu3+ nanocrystals samples, the energy transfer effect from Sm3+ ions to Eu3+ ions was completed, and the fluorescence emissions originating from the 5D0 level of Eu3+ were observed. The luminescence properties of the LaOF: Sm3+/Eu3+ nanocrystals system were analyzed with a spectroscopic method, and the mechanism and dynamic process of the energy transfer were explored. It was found that the efficiency of the energy transfer increase with the increase in the concentration of Eu3+ ions and the size of nanocrystals.

Carcinoma arising in microglandular adenosis (MGACA) is an extremely rare subtype of breast carcinoma. In this study, clinicopathological analysis of MGACA from 11 Chinese patients was conducted. Microscopically, all cases showed a spectrum of structure and glandular proliferations ranging from MGA to atypical MGA (AMGA) to MGACA. Carcinoma components were composed of high grade ductal carcinoma in situ (DCIS) in one case and invasive carcinoma in 10 cases. Invasive carcinomas were grade 3 in 10 tumors and grade 2 in one. Invasive components in five of 10 cases were composed of invasive carcinoma of no special type (NST), and one case showed prominent oncocytic change in a considerable portion of epitheliums. In five cases, invasive components were mixed of NST and matrix-producing carcinoma (MPC). All epitheliums in 11 cases were triple negative (ER-, PR-, HER2-), and diffuse positive for CK and S-100 protein. Ki-67 proliferation index ranged from 30% to 70%. No myoepithelial cells were demonstrable from MGA to invasive components with immunohistochemical staining for P63 and calponin. PAS or reticulin stain showed the presence of a basement membrane around glands in MGA, AMGA, DCIS, and its absence in invasive components. Follow-up time ranged from 8 to 62 months. One patient developed a lung metastasis 24 months after surgery, 10 patients have been alive without recurrence. Our study revealed that MGACA is a distinct subset of breast carcinoma, with triple negative phenotype, high grade nuclear and variable morphology. Despite histopathologic and immunohistochemical features usually associated with a poor prognosis, MGACA seems to have a relatively favorable outcome.

Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of 73 cases of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were evaluated. Invasive carcinoma of no special type was the most common histological type in the study group (71.2%, 52/73). The luminal A and B subtypes were the major types of male breast carcinoma (60.9%, 34.8% respectively). AR and FOXP1 are expressed in 84.2% (48/57) and 71.9% (41/57) of the studied cases. Carcinoma of the luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than cases of the luminal B subtypes (34.8%, 8/23 and 43.5%, 10/23, respectively; P = 0.004, P = 0.255, respectively). In conclusion, invasive carcinoma of no special type was the most common histological type in male breast carcinoma among Chinese population. Our study revealed that the luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 are highly expressed in male breast cancer. The luminal A subtype tends to express GCDFP15 and MGB more frequently than the luminal B subtype.

Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.

Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.