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Brassinosteroid (BR) is an essential phytohormone that controls plant growth. However, the mechanisms of BR regulation of leaf size remain to be determined. Here, we found that the BR deficient cotton mutant pagoda1 (pag1) had a smaller leaf size than wild-type CRI24. The expression of EXORDIUM (GhEXO2) gene, was significantly downregulated in pag1. Silencing of BRI1-EMS-SUPPRESSOR 1 (GhBES1), inhibited leaf cell expansion and reduced leaf size. Overexpression of GhBES1.4 promoted leaf cell expansion and enlarged leaf size. Expression analysis showed GhEXO2 expression positively correlated with GhBES1 expression. In plants, altered expression of GhEXO2 promoted leaf cell expansion affecting leaf size. Furthermore, GhBES1.4 specifically binds to the E-box elements in the GhEXO2 promoter, inducing its expression. RNA-seq data revealed many down-regulated genes related to cell expansion in GhEXO2 silenced plants. In summary, we discovered a novel mechanism of BR regulation of leaf size through GhBES1 directly activating the expression of GhEXO2.

Abstract: Flavonoids, a series of compounds with C6-C3-C6 structure, mostly originate from plant metabolism. Flavonoids have shown beneficial effects on many aspects of human physiology and health. Recently, many flavonoids with various activities have been discovered, which has led to more and more studies focusing on their physiological and pharmacodynamic activities. The anti-cancer and anti-viral activities especially have attracted the attention of many researchers. Therefore, the discovery and development of flavonoids as anti-disease drugs has great potential and may make significant contribution to fighting diseases. This review focus on the discovery and development of flavonoids in medicinal chemistry in recent years.

Mingji Jin,1,2,* Yan Hou,1– 3,* Xiuquan Quan,1,2,4,* Liqing Chen,1,2 Zhonggao Gao,1,2 Wei Huang1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China; 3Department of Pharmacy, Yanbian University, Yanji, Jilin, 133000, People’s Republic of China; 4Department of Emergency Medicine, Affiliated Hospital of Yanbian University, Yanji, Jilin, 133000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhonggao Gao; Wei Huang Tel +86 010 63028096; +86 010 63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: The dual-loaded nano-delivery system can realize chemotherapeutic drug and small interfering RNA (siRNA) co-loading as well as enhance the therapeutic effect of drugs on tumors through a synergistic effect, while reducing their toxic and side effects on normal tissues.Methods: Previously, we developed layered smart nanoparticles (NPs) to co-deliver survivin siRNA as well as small molecule drugs for lung cancer. In this study, we used such smart NPs to co-deliver paclitaxel (PTX) and siRNA against vascular endothelial growth factor (VEGF) gene for breast cancer therapy in mice models. For the prepared NPs, characterizations such as particle size, zeta potential, gel electrophoresis imaging and in vitro stability were investigated. Then, 4T1 cells were used to evaluate the in vitro VEGF silencing capacity, tumor cell inhibitory and anti-apoptotic abilities. Finally, an orthotopic model of mouse breast cancer was established to evaluate the in vivo antitumor effects and safety properties of PTX-siRNAVEGF-NPs.Results: We prepared PTX-siRNAVEGF-NPs with particle size of 85.25 nm, PDI of 0.261, and zeta potential of 5.25 mV. The NPs with VEGF siRNA effectively knocked down the expression of VEGF mRNA. Cell counting kit-8 (CCK-8) and apoptosis assays revealed that the PTX-siRNAVEGF-NPs exhibited antiproliferation effect of PTX on 4T1 cells. The in vivo anti-tumor study indicated that PTX-siRNAVEGF-NPs could exert an antitumor effect by inhibiting the formation and development of new blood vessels in tumor tissues, thereby cutting off nutrient and blood supplies required for tumor tissue growth. Both the anti-tumor efficacy and in vivo safety of the PTX-siRNAVEGF-NPs group were better than that of the PTX-NPs and siRNAVEGF-NPs groups.Conclusion: The combination of PTX and VEGF siRNA exerts good antitumor effect on 4T1 tumor cells. This study provides a theoretical and practical basis for breast cancer therapy.Keywords: paclitaxel, VEGF siRNA, breast cancer, co-delivery

This study developed a simple, rapid, stable, and reliable technique for acrylamide (AAm) detection through surface-enhanced Raman scattering (SERS) on an AgNPs substrate with an aggregating agent. Specifically, the agglomeration effects of five types of salt solutions (NaCl, KCl, MgCl

The aim of this study was to determine the expression of long-chain non-coding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) in children with neuroblastoma and its effect on cancer cell growth. A polymerase chain reaction assay was carried out to quantify lncRNA CCAT2 miRNA in neuroblastoma cells, corresponding paracancerous cells, SH-SY5Y and SK-N-SH cells, and human umbilical vein endothelial cells (HUVEC), and two groups of children with different lncRNA CCAT2 expression were compared in clinical pathological parameters and prognosis. CCAT2-NC and si-CCAT2 were transfected into SH-SY5Y cells, separately. Then a 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay was carried out to analyze the cell proliferation, migration, and invasion ability, a flow cytometry to detect cell apoptosis, and a Western blotting (WB) assay to quantify p53 and Bcl-2 proteins. lncRNA CCAT2 expression in cancer tissues of children with neuroblastoma was notably higher than that in corresponding paracancerous tissues (P

This study aimed to investigate the inhibitory effect of EM-2, a natural active monomer purified from Elephantopusmollis H.B.K., on the proliferation of human hepatocellular carcinoma cells and the molecular mechanism involved. The results from the MTT assay revealed that EM-2 significantly inhibited the proliferation of human hepatocellular carcinoma (HCC) cells in a dose-dependent manner but exhibited less cytotoxicity to the normal liver epithelial cell line LO2. EdU staining and colony formation assays further confirmed the inhibitory effect of EM-2 on the proliferation of Huh-7 hepatocellular carcinoma cells. According to the RNA sequencing and KEGG enrichment analysis results, EM-2 markedly activated the MAPK pathway in Huh-7 cells, and the results of Western blotting further indicated that EM-2 could activate the ERK and JNK pathways. Meanwhile, EM-2 induced apoptosis in a dose-dependent manner and G2/M phase arrest in Huh-7 cells, which could be partially reversed when treated with SP600125, a JNK inhibitor. Further study indicated that EM-2 induced endoplasmic reticulum stress and blocked autophagic flux in Huh-7 cells by inhibiting autophagy-induced lysosome maturation. Inhibition of autophagy by bafilomycin A1 could reduce cell viability and increase the sensitivity of Huh-7 cells to EM-2. In conclusion, our findings revealed that EM-2 not only promoted G2/M phase arrest and activated ER stress but also induced apoptosis by activating the JNK pathway and blocked autophagic flux by inhibiting autolysosome maturation in Huh-7 hepatocellular carcinoma cells. Therefore, EM-2 is a potential therapeutic drug with promising antitumor effects against hepatocellular carcinoma and fewer side effects.

Objective Shenling Baizhu powder (SBP) has been shown to reverse the abnormal expression of the aromatic hydrocarbon receptor (AHR) mediated by air pollution. Our study aimed to understand the main ingredient of SBP and investigate its action mechanism in preventing polycystic ovary syndrome (POCS) and postmenopausal osteoporosis (PMO). Methods The active ingredients of SBP with the highest binding affinity to AHR were screened using a Chinese medicine database, and their binding mechanism was simulated using molecular dynamics simulation (MDS). Rutin was utilized to treat ovarian granulosa cell lines and osteoblast cell lines. The cell lines were treated with a gradient of rutin concentration (0.01 mmol/L, 0.05 mmol/L and 0.1 mmol/L) to find the optimal drug dose. PCR was used to detect AHR and apoptosis-related proteins, and WB to detect the expression of AHR, caspase-3 and cleaved-caspase-3. Finally, the CCK-8 cell proliferation assay detected the proliferation of cells. Results We obtained Rutin through the Chinese medicine database, and dynamics simulation determined its binding sites. Ovarian granulosa cell lines and osteoblast cell lines were treated with Rutin. RT-PCR and western blotting revealed that the expression of apoptosis-associated protein Bcl-2 was elevated, and the expression of AHR, Bax, caspase-3 and PARP were decreased. CCK-8 results showed accelerated proliferation in both cell types. Conclusion Rutin, the main ingredient of SBP compound, works by binding to AHR, which can improve POCS and PMO by inhibiting cell apoptosis and by promoting cell proliferation.

Lung cancer is the leading cause of cancer mortality, and early detection is key to improving survival. However, there are no reliable blood-based tests currently available for early-stage lung cancer diagnosis. Here, we performed single-cell RNA sequencing of different early-stage lung cancers and found that lipid metabolism was broadly dysregulated in different cell types, with glycerophospholipid metabolism as the most altered lipid metabolism–related pathway. Untargeted lipidomics was carried out in an exploratory cohort of 311 participants. Through support vector machine algorithm-based and mass spectrum–based feature selection, we identified nine lipids (lysophosphatidylcholines 16:0, 18:0, and 20:4; phosphatidylcholines 16:0–18:1, 16:0–18:2, 18:0–18:1, 18:0–18:2, and 16:0–22:6; and triglycerides 16:0–18:1–18:1) as the features most important for early-stage cancer detection. Using these nine features, we developed a liquid chromatography–mass spectrometry (MS)–based targeted assay using multiple reaction monitoring. This target assay achieved 100.00% specificity on an independent validation cohort. In a hospital-based lung cancer screening cohort of 1036 participants examined by low-dose computed tomography and a prospective clinical cohort containing 109 participants, the assay reached more than 90.00% sensitivity and 92.00% specificity. Accordingly, matrix-assisted laser desorption/ionization MS imaging confirmed that the selected lipids were differentially expressed in early-stage lung cancer tissues in situ. This method, designated as Lung Cancer Artificial Intelligence Detector, may be useful for early detection of lung cancer or large-scale screening of high-risk populations for cancer prevention.

Colorectal cancer (CRC) is the most common human digestive malignancy with a poor prognosis; the pathophysiology of colon cancer involves multiple linkages of regulatory networks. Recently, thrombospondin 2 (THBS2) has been extensively studied for its role in cancer progression. In this study, we evaluated the expression of THBS2 in CRC tissues and studied the possible mechanism by which THBS2 regulates CRC progression. Our results showed that the upregulation of THBS2 in CRC tissues and CRC cell lines and high expression of THBS2 was correlated with poor overall survival. The in vitro experimental data showed that THBS2 overexpression promoted CRC cell growth, invasion, and migration, while THBS2 inhibition exerted tumor-suppressive actions on CRC cells. THBS2 knockdown suppressed the activity of Wnt/β-catenin signaling. Collectively, the results implied that THBS2 exerted promotional effects on CRC cell proliferation, invasion, and migration, partly by modulating the Wnt/β-catenin signaling pathway.

To investigate the auditory pathway functions in deaf patients with Mondini malformation using the electrically evoked auditory brainstem response (EABR) during cochlear implantation (CI).A total of 58 patients with severe to profound sensorineural hearing loss (SNHL) were included in this study. Of these patients, 27 cases had Mondini malformation and 31 control cases had no inner ear malformations (IEMs). Intraoperative EABRs evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded.Patients with Mondini malformation showed significantly lower EABR extraction rates than those with no IEMs did. However, for patients who showed EABRs, no significant difference in EABR thresholds, wave III (eIII) latencies, wave V (eV) latencies or eIII-eV latency intervals was found between two groups.The physiological functions of the peripheral auditory system in patients with Mondini malformation may divide into opposite extremes, as revealed by a robust EABR and the absence of the EABR, respectively. The auditory conduction function should be objectively and individually evaluated for patients with Mondini malformation by the EABR.

Casein kinase-2 interaction protein-1 (Ckip-1) is a negative regulator of bone formation. The identification of novel Ckip-1-related targets and their associated signaling pathways that regulate mesenchymal stem cell (MSC) osteogenic differentiation is required. The present study aimed to evaluate the effects of Ckip-1 knockdown on C3H10T1/2 MSC proliferation and osteogenic differentiation, and to explore the role of the canonical Wnt-signaling receptor Lrp5. Ckip-1-knockdown (shCkip-1), Ckip-1-overexpression (Ckip-1) and their corresponding control [shCtrl and empty vector (EV), respectively] cell groups were used in the present study. Immunofluorescence localization of Ckip-1 was observed. The expression of the key molecules of the canonical Wnt signaling pathway was examined in C3H10T1/2 cells following osteogenic induction. Moreover, the effects of Lrp5 knockdown in the presence or absence of Ckip-1 knockdown were examined on C3H10T1/2 cell proliferation and osteogenic differentiation. The results indicated an increase in cell proliferation and osteogenic differentiation in the shCkip-1 group compared with the shCtrl group. The expression levels of LDL receptor related protein 5 (Lrp5), lymphoid enhancer binding factor 1 (Lef1) and transcription factor 1 in C3H10T1/2 cells were significantly increased in shCkip-1 cells following 7-day osteoinduction compared with shCtrl cells. Moreover, the involvement of Lrp5 in shCkip-1-induced osteogenic differentiation of C3H10T1/2 cells was further verified. The results indicated that Ckip-1 reduced C3H10T1/2 MSC proliferation and osteogenic differentiation via the canonical Wnt-signaling receptor Lrp5, which is essential for the improvement of bone tissue engineering.

Highlights • At the beginning of the epidemic, measures to lockdown the city could reduce imported spread. • Household transmission is not yet controlled, particularly for the infection of imported cases to elderly women. • Patients who contacted with a confirmed case of family members were admitted to the hospital earlier. • Surveillance and education of immediate admission/isolation should be emphasized, after travel restrictions were taken., Background As COVID-19 ravages continuously around the world, more information on the epidemiological characteristics and factors associated with time interval between critical events is needed to contain the pandemic and to assess the effectiveness of interventions. Methods Individual information on confirmed cases from January 21 to March 2 was collected from provincial or municipal health commissions. We identified the difference between imported and local cases in the epidemiological characteristics. Two models were established to estimate the factors associated with time interval from symptom onset to hospitalization (TOH) and length of hospital stay (LOS) respectively. Results Among 7,042 cases, 3392 (48.17%) were local cases and 3304 (46.92%) were imported cases. Since the first intervention was adopted in Hubei on January 23, the daily reported imported cases reached a peak on January 28 and gradually decreased since then. Imported cases were on average younger (41 vs. 48), and had more male (58.66% vs. 47.53%) compared to local cases. Furthermore, imported cases had more contacts with other confirmed cases (2.80 ± 2.33 vs. 2.17 ± 2.10), which were mainly within family members (2.26 ± 2.18 vs. 1.57 ± 2.06). The TOH and LOS were 2.67 ± 3.69 and 18.96 ± 7.63 days respectively, and a longer TOH was observed in elderly living in the provincial capital cities that were higher migration intensity with Hubei. Conclusions Measures to restrict traffic can effectively reduce imported spread. However, household transmission is still not controlled, particularly for the infection of imported cases to elderly women. It is still essential to surveil and educate patients about the early admission or isolation.

Cancer cell resistance to current anticancer therapeutics as well as the side effects are still obstacles to successful cancer therapy. Hence, the development of novel anticancer agents or therapeutics is of vital significance, and especially rational adjuvant therapies containing low-cost natural products with multiple targets have attracted great interests. Triptolide, the main biocomponent of Tripterygium wilfordii Hook F, is restricted in clinical applications mainly due to its severe systemic toxicities, although it has shown strong antitumor activities in preclinical studies. Mounting evidence suggests that triptolide at low doses as an adjuvant therapeutic agent circumvents resistance to current anticancer therapies, enhances the anticancer effectiveness, and relieves toxicities of both triptolide and anticancer therapies. Furthermore, several unique antitumor targets of triptolide make it superior to other therapeutics. The molecular mechanisms of triptolide-induced anti-resistance and sensitization effects include changes in ATP-binding cassette transporters, induction of apoptosis pathways, increase in tumor suppressors and decrease in oncogenic factors, and interactions with the RNA polymerase II complex; targeting cancer stem cells and tumor-microenvironment-mediated resistance are also involved. Besides, some synthetic derivatives and novel delivery systems of triptolide are also developed to enhance the water-solubility and reduce the toxicity, which will also be discussed.

A size-segregated gas/particle partitioning coefficient KPi was proposed and evaluated in the predicting models on the basis of atmospheric polybrominated diphenyl ether (PBDE) field data comparing with the bulk coefficient KP. Results revealed that the characteristics of atmospheric PBDEs in southeast Shanghai rural area were generally consistent with previous investigations, suggesting that this investigation was representative to the present pollution status of atmospheric PBDEs. KPi was generally greater than bulk KP, indicating an overestimate of TSP (the mass concentration of total suspended particles) in the expression of bulk KP. In predicting models, KPi led to a significant shift in regression lines as compared to KP, thus it should be more cautious to investigate sorption mechanisms using the regression lines. The differences between the performances of KPi and KP were helpful to explain some phenomenon in predicting investigations, such as PL0 and KOA models overestimate the particle fractions of PBDEs and the models work better at high temperature than at low temperature. Our findings are important because they enabled an insight into the influence of particle size on predicting models.

The study aimed to compare the efficacy of intra-arterial methotrexate (MTX) infusion combined with uterine artery embolisation (UAE) and uterine curettage with that of UAE and curettage without MTX infusion for the treatment of cesarean scar pregnancy (CSP). In this retrospective study, data of CSP patients admitted from January 2011 to July 2015 were obtained from electronic patient records. Clinical information at baseline and after treatment were extracted and analyzed. A total of 93 CSP patients were included, with 57 patients receiving UAE followed by curettage (UC) and 36 patients receiving intra-arterial MTX infusion followed by UAE and curettage (MUC). The baseline characteristics were not significantly different between the two groups. Without additional intervention, 32 (88.9%) patients were successfully treated by MUC, and 49 (86.0%) patients were successfully treated by UC, defined by discontinued ectopic conceptus growth, normalized serum β-human chorionic gonadotropin (β-hCG) level, ceased vaginal bleeding and preservation of uterus, with no significant difference between the two groups. Additionally, intra-operative blood loss volume and post-operative bleeding events were not significantly different between the two groups. However, serum β-hCG decline on the first day after surgery was significantly promoted, and the hospitalization length and the time needed for serum β-hCG normalization were significantly shortened by addition of intra-arterial MTX infusion. Adding intra-arterial MTX to UAE and curettage significantly promoted post-operative recovery, though success rate and bleeding events were not significantly affected, suggesting that addition of intra-arterial MTX might not be necessary.

As an important herbaceous plant, Scutellaria baicalensis Georgi (Chinese skullcap) is geographically widespread and commonly used throughout the world. In the Chinese medicine market, S. baicalensis has been divided into two primary types, "Ku Qin" (WXR) and "Tiao Qin" (TST). Moreover, TST is also divided into different grades according to the diameter of roots. To explore the distribution patterns of the contents of five biologically activate ingredients (FBAI), we used six-year-old cultivated S. baicalensis and analyzed its growth characteristics as well as the quality difference among different types and diameters in roots. Throughout the entire root, we discovered that contents of the FBAI all initially increased and subsequently decreased from the top to the bottom of the roots. The baicalin content of WXR was less than that of TST. On the contrary, the contents of baicalein, wogonin, and oroxylin A in WXR were up to about two times higher than that in TST. We also found that the 0 to 40 cm part of the S. baicalensis root possessed about 87% of the root biomass and about 92% of the contents of the active ingredients.

Background In the present work, we investigated the effects of aqueous extract of Maca (AEM) on energy metabolism and immunoregulation in spleen-deficient mice. Method We established a cyclophosphamide-induced spleen-deficiency model with ginseng, a herb that strengthens splenic function, as a control. Sixty male Kunming mice were randomly divided among 5 groups: normal, model, ginseng control (1.5 g/kg), AEM high dose (1.5 g/kg), and AEM low dose (0.75 g/kg). All animals, except those in the normal group, were injected with cyclophosphamide to induce spleen deficiency. Furthermore, we investigated differences in the thermotropic behaviors of mice using the Animal Thermotropism Behavior Surveillance System to detect energy metabolism-related assays and immune regulation assays. Results Mice given AEM exhibited tropism in response to hot plate exposure. AEM inhibited loss of body weight and immune organ atrophy caused by cyclophosphamide, increased the cAMP/cGMP ratio in blood, and enhanced the activities of Na+–K+-ATPase, Ca2+–Mg2+-ATPase, lactate dehydrogenase, and hepatic glycogen. AEM significantly reversed declining white blood cells and platelet counts, and increased the hemoglobin content within peripheral blood cells. AEM improved the protein levels of IFN-γ, TNF-β, IL-2, and IL-4 in the spleen. Conclusions Maca possesses the Traditional Chinese Medicine (TCM) property of warm and appears to strengthen spleen function.

Recurrent pregnancy loss (RPL) is three or more times of consecutive spontaneous loss of pregnancy. The underlying cause is complicated and the etiology of over 50% of RPL patients is unclear. In the present study, bone marrow mesenchymal stem cells were isolated from CBA/J female mice and exosomes were isolated from cell culture medium by ultracentrifugation. CBA/J female mice were paired with male DBA/2 to generate abortion prone mouse model, and CBA/J females paired with male BALB/c mice were used as control. Exosomes were injected through uterine horns into pregnant CBA/J mice on day 4.5 of gestation in abortion‐prone matting. On day 13.5 of pregnancy, abortion rates were calculated and the level of transforming growth factor‐β (TGF‐β), interleukin 10 (IL‐10), interferon g (IFN‐γ), and tumor necrosis factor a (TNF‐α) in CD4+ T cells and macrophages in deciduas were evaluated by flow cytometry. Exosomes injection improved the pregnancy outcomes in abortion prone mice. The IL‐4 and IL‐10 levels on CD4+ T cells were upregulated in the maternal–fetal interface; meanwhile, the TNF‐α and IFN‐γ levels on CD4+ T cells were reduced. The IL‐10 level was increased and IL‐12 was reduced on the monocytes that separated from deciduas. miR‐101 level was increased in the CD4+ T cells in the deciduas. In conclusion, the treatment of ESCs‐derived exosomes modulates T cells' function and macrophages activities in the maternal–fetal interface that resulted in a decreased embryo resorption rate, and provides a therapeutic potential to treat RPL.

Background Leishmania parasites cause visceral leishmaniasis (VL), an important infectious disease that is endemic to large parts of the world and often leads to epidemics. Sand flies are the primary transmission vector for the parasite in endemic regions. We hypothesized that sheep might serve as an overlooked reservoir for Leishmania transmission to humans due to the asymptomatic nature of infection in many species. As a preliminary test of this hypothesis, the aim of the present study was to investigate sheep in an area of China that is endemic for the desert sub-type of zoonotic VL and establish if they are potential carriers of Leishmania. Results Sheep tissue samples were collected from abattoirs in VL endemic areas of Jiashi County, China during the non-transmission season. rK39 immunochromatographic tests were performed to detect the presence of the parasite in blood samples. In addition, DNA was extracted from the blood, and used for detection of the Leishmania-specific internal transcribed spacer-1 (ITS-1) genomic region using a nested polymerase chain reaction (PCR) approach. PCR products were further analyzed to identify restriction fragment-length polymorphism patterns and representative sequences of each pattern were selected for phylogenetic analysis. The rK-39 and nested PCR data indicated positive detection rates for Leishmania in sheep of 26.32 and 54.39%, respectively. The phylogenetic analysis revealed that all of the samples belonged to the species L. infantum and were closely related to strains isolated from human infections in the same area. Conclusions Sheep could be a potential host for Leishmania in VL endemic areas in China and may be an overlooked reservoir of human VL transmission in this region. To further confirm livestock as a potential host, further verification is required using a sand fly biting experiment.

Doxorubicin (DOX), a potent and widely used anticancer agent, can give rise to severe cardiotoxicity that limits its clinical use by inducing oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the central regulator of cellular responses to electrophilic/oxidative stress, which serves a critical role in maintenance of normal cardiac function. Tanshinone IIA (Tan IIA) has previously been reported to protect against DOX-induced cardiotoxicity. The aim of the present study was to elucidate whether Nrf2 signaling serves a role in the underlying mechanism. In the animal model, DOX induced acute cardiotoxicity, whereas Tan IIA pretreatment reduced the activity of myocardial enzymes, and increased activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione (GSH). Furthermore, Tan IIA pretreatment (3-10 µM) significantly increased the cell viability and markedly restored morphological changes in DOX-injured H9c2 cells, decreased the generation of reactive oxygen species, and increased the level of intracellular GSH. Additionally, Tan IIA pretreatment also induced the nuclear accumulation of Nrf2 and its downstream genes heme oxygenase-1, NAD(P)H dehydrogenase (quinone) 1, and glutamate-cysteine ligase catalytic subunit in both the mice cardiac tissues and H9c2 cells. Nrf2 knockdown by small interfering RNA downregulated Tan IIA-induced Nrf2 activation and reversed the effect of Tan IIA on the DOX-induced inhibition of cell viability. These results suggest that the Nrf2-dependent antioxidant response mediates the protective effect of Tan IIA on DOX-induced cardiotoxicity.

Background Gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS) metabolomics have been deployed to detect novel differential metabolites in cases with recurrent spontaneous abortion (RSA). Material/Methods Fifty patients who had recurrent spontaneous abortions (RSAs) and 51 control patients (age, gestational age, and body mass index (BMI) match) were enrolled in this study. Untargeted GC-MS and targeted LC-MS were combined to discover and validate the different metabolomic profiles between groups. Score plots of orthogonal partial least-squares discriminant analysis (OPLS-DA) clearly separated the RSA group from the control group. The variable importance in projection (VIP) generated in OPLS-DA processing represented the contribution to the discrimination of each metabolite ion between groups. Variables with a VIP >1 and P1 and P

The efficient fermentation of xylose can improve biofuel production. We previously developed a two-stage transcriptional reprogramming (TSTR) strategy (including a glucose fermentation stage and a xylose fermentation stage) and demonstrated its application for the construction of Saccharomyces cerevisiae strains with efficient xylose utilization. In this study, we used these as initial strains to assess the effects of copy number variation (CNV) on optimal gene expression and rewiring the redox balance of the xylose utilization pathway. We obtained strains that contained several integrated copies of XYL1, XYL2, and XKS1 and showed increased ethanol yields. An examination of the individual and combined effects of CNVs of key genes and the redox balance pathway revealed that the TSTR strategy improves ethanol production efficiency. Furthermore, XYL1 or XYL2 overexpression was related to improved xylose utilization. These results showed that strains with faster growth and/or higher ethanol production produced more ethanol from xylose via the synthetic xylose-assimilation pathway. Accordingly, TSTR is an effective strategy to improve xylose metabolism in industrial yeast strains.

Supplemental Digital Content is available in the text, Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases. A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants. The Sanger sequencing method was used to verify the candidate mutation. WES yielded 2,238,831 variations. KCNJ12 (p.Glu334del) was identified as a candidate mutation, and the heterozygous mutation was verified by Sanger sequencing. Our study emphasizes the application of WES in identifying causative mutations in DCM. This report is the first to describe the KCNJ12 gene as a cause of DCM in patients.

Conclusions The straight electrode array with length of 31 mm can be fully inserted using round window insertion in cochlear implantation with Mondini's deformity. It is a safe and effective process, but also a challenging task of the full implantation in children with Mondini's deformity. Objective The aim of this study is to discuss whether the straight electrode array with a length of 31 mm could be fully inserted in cochlear implantation with Mondini's deformity. Methods A chart review of 30 patients undergoing cochlear implantation with Mondini's deformity using the electrode array with length of 31 mm was undertaken from January 2012 and December 2015 in Anhui Provincial Hospital. Results Full insertion of the straight electrode array with length of 31 mm were performed successfully in all patients with Mondini's deformity using round window insertion. Resistance was not encountered while introducing the electrodes. Ten of 30 patients had cerebrospinal fluid drainage during cochlear implantation. Cerebrospinal fluid drainage was controlled with small pieces of temporalis fascia packing round window in all patients. Intra-operative neural response telemetry was performed in all patients, and results were good. The result of X-ray showed proper placement of the cochlear implant electrode array. During surgery, no patients had experienced any immediate or delayed post-operative complications such as wound infection, intracranial complication, extrusion, or migration of the implant during an average follow-up period of 6-36 months.

As a new social networking media, Micro-blog is recognized by more and more people gradually, the orientation analysis of Micro-blog short text messages has become a hotspot in the field of data mining. At present, the research of Micro-blog orientation analysis mainly concentrate in the text, without considering the impact of other emotional factors. By analyzing and studying Sina Micro-blog, this paper added new words and emoticons in the basis of traditional emotional dictionary to construct special Micro-blog dictionary. Meanwhile, it analyzed rhetoric and sentence to improve the effect of orientation analysis. The experimental results showed that the method in Micro-blog orientation analysis obtained better performance.

The key of swirling airflow finishing is how to generate the swirling airflow. In the paper, three swirling airflow head are discussed according the manners of tangential inflow. By means of FLUENT, the general software of CFD, the swirling airflow field from different airflow head is simulated. The simulation results are shown by the flow line graphs, tangential velocity, radial distribution graphs, etc. All we have studied is as the basis for the determination of the application scope of each swirling airflow head.

This paper studies the control of a two-wheeled vehicle which is similar to an inverted pendulum system and has hand sensors to make right and left turns. Because the two-wheeled vehicle is unstable and its load is uncertain, PID and LQR controllers are used to stabilize the uncertain and unstable plant. Moreover, the two controllers can make it move forwards and backwards, and turn left and right. The two controllers are implemented into a microcontroller, and the microcontroller outputs appropriate control signals to drive the two-wheeled vehicle according to the three-axis accelerometer and gyroscope sensors. Finally, we verify the controllers' efficiency and compare the difference between above two controllers.

In response to hepatitis B surface antigen colloidal gold strip rapid analyzer application characteristics, design a new type hepatitis B fast analyzer control system using the embedded method. The control system based on ARM-DSP dual-core architecture, with low power consumption, small volume, anti interference, for hepatitis B surface antigen colloidal gold strip rapid analyzer is miniaturized and portable design foundation.

According to the operator experiences, the variable rate fertilization system based on the fuzzy self-tuning PID controller is researched in this paper, which is driven by electrically and hydraulic system. This system solves the problem that the parameters adjustment of the traditional PID is difficult. The system model is presented and is simulated by using MATLAB/ SIMULINK toolbox. The simulation results shows that the fuzzy self-tuning PID control could obtain better dynamic response and achieve the expected control effects. In order to verify this control system performance, many experiments are carried on in the lab. The experiments results show that the variable rate fertilization system based on fuzzy self-tuning PID control has high control accuracy and could meet the control requirements of the variable rate fertilization in precision agriculture.

Transmission lines pass through various types of regions in China and some of that are corrosive. The foundation concrete of transmission lines in corrosive environments had shown serious deterioration, which usually caused by concrete deterioration, rebar corrosion, degradation of bond strength between rebar and concrete due to various corrosive effects. There are salt lake areas in west China where some power transmission channels pass through. Field tests are carried out in Golmud area to research the durability of foundation concrete of transmission lines. And test results show that the concrete strength in the air is higher than underground and the carbonation depth of the foundation concrete decreases with the increase of concrete compressive strength.

A novel face detection approach based on double skin models and AdaBoost algorithm is proposed in this paper. The image segemention of skin regions is firstly got with a fixed threshold skin model in YCbCr color space. The image segemention result is used for optimizing the parameters of Gaussian skin color model which is used for the image segmentation of the skin regions secondly. The logical operations are computed with the twice results of skin segmentation and then the coarse position of candidate face regions are got by morphological processing. Finally, the accurate face regions are acquired combined with Adaboost algorithm. The experimental results indicate that this face detection method can restrain the false number better on the premise that a proper detection rate should be kept and has better robustness.

Content-based video hashing was proposed for the purpose of video copy detection. Conventional video copy detection algorithms apply image hashing algorithm to either every frame or key frame which is sensitive to video variation. In our proposed algorithm, key frames including temporal and spatial information are used to video copy detection, Discrete cosine transform (DCT) is done for video key frame and feature vector is extracted by principal component analysis ( PCA ). An average true positive rate of 99.31% and false positive rate of 0.37% demonstrate the robustness and uniqueness of the proposed algorithm. Experiments indicate that it is easy to implement and more efficient than other video copy detection algorithms.

An electronic differential control system (EDS) has been designed based on a mini electric vehicle (EV) with dual in-wheel-motor rear drive. In view of imperfection of current strategy with speed and moment as control variables, a new control strategy for EDS in a two in-wheel-motor drive EV is proposed with the moment of driving wheel torque as control variable and the slip rate equilibrium of two driving wheels as control objective, considering the effects of axle load transfer. The differential control experiments are conducted with steering mode and straight acceleration mode based on the vehicle prototype. The results show that the control strategy is reasonable, and the controller can effectively realize EV electronic differential by coordinating the moment of two driving wheels.

The chemical shift is sensitive to changes in the local environments and can report the structural changes. The structure information of a protein can be represented by the average chemical shifts (ACS) composition, which has been broadly applied for enhancing the prediction accuracy in protein subcellular locations and protein classification. However, different kinds of ACS composition can solve different problems. We established an online web server named acACS, which can convert secondary structure into average chemical shift and then compose the vector for representing a protein by using the algorithm of auto covariance. Our solution is easy to use and can meet the needs of users.

Parameters of Support Vector Machine are playing an important part in learning performance and generalization capability. The randomness and blindness in selecting SVM model parameters artificially could be eliminated by using group intelligent optimizing algorithm. FOA is a kind of group intelligent optimization algorithm. It has some advantages such as global convergence, connotative parallelism and fast operating speed. However, its optimum efficiency is very sensitive to the length of fixed step. In the course of optimizing, if the step is oversize, it will have preferable global optimizing performance and weak local optimizing capability. On the contrary, if the step is undersize, the local optimizing capability would be powerful and it will have the most probability to lapse into local extreme value. Therefore, a kind of algorithm named Diminishing Step FOA is proposed, the step length minishes progressively along with the process of foraging. So that it would have preferable global optimizing capability in early stage and preferable local optimizing capability in later period. And then, a dynamic balance will be achieved between global and local optimizing capability. The experimental results show that the SVM model using DS-FOA has optimal forecast precision and effect.

Hydrogen peroxide production via cathodic reduction of oxygen on self-made gas diffusion electrode was investigated in an undivided electrochemical system. The effects of mass ratio between graphite and PTFE in cathode, the calcination temperature, current density, pH, and plate distance on hydrogen peroxide generation were discussed. The results showed that the self-made gas diffusion cathode had high catalyze capacity for production of hydrogen peroxide using cathodic oxygen-reducing reaction. The hydrogen peroxide concentration could reach 80.52 mg·L- 1 within 2 h. The optimal conditions for this system are as follows: mass ratio of graphite to PTFE in cathode, 21, calcination temperature, 300 °C, current density,4.69mA/cm2, pH 13.0, and the distance between anode and cathode, 8cm. The high concentration of hydrogen peroxide generated gives a promising application of this novel gas diffusion electrode system in pulp bleaching and waste-water treatment.

Autism spectrum disorders are a member of the pervasive developmental disorders (PDDs) that have been increasing dramatically since described by Leo Kanner in 1943. In the past decade, the number of epidemiological publications addressing air pollution exposures and autism has grown correspondingly, but the association is still unclear. Whether air pollutants play a causal role and which substances are related with autism requires further study. We systematically reviewed the literature from 2005 to 2016 in MEDLINE (National Library of Medicine), Web of Science, and PubMed and summarized the association between different air pollutants and autism. Furthermore, we further discussed the exposure time window and potential confounders that should be considered in the association analysis studies. Our objective is to summarize the association between different air pollutants and autism with literature, which has been published since 2005, and explore whether the exposure time window and potential confounders have influence on this association. These results could provide more comprehensive information about the association between air pollutants and autism and be helpful towards further validation study. Graphical abstract ᅟ.

Conclusions: Cochlear implantation (CI) with round window insertion could be performed safely and effectively in children less than 2 years old, but it is a more challenging operation. Objective: To discuss the key surgical techniques of CI in children less than 2 years old with profound sensorineural hearing loss. Methods: This was a retrospective study of data collected from patients undergoing CI. CI was performed with round window insertion in children less than 2 years old in Anhui Provincial Hospital between January 2003 and May 2013. Results: CI was performed in a total of 85 children. Of these, 80 children (90%) had round window insertion. All children had full insertions of the electrode array, in which the CI went normally and the electrode array was protected well. All implant devices worked normally and all patients performed well during an average follow-up period of 6–36 months. No major or minor complications occurred, and there was no perioperative anesthetic complication.

Drilling samples of lunar soil is an important and indispensable part of Chinas lunar exploration project. The drill bit temperature during the drilling process is one of the key concerns for scholars, especially for the hard lunar rock drilling in vacuum environment. In this article, a fiber grating temperature measurement system integrated with vacuum drilling system is established. Experiment on simulated lunar rock in atmospheric and vacuum environments is taken out and compared.

This paper investigates the performance enhancement of a newly designed stack ultrasonic motor by using PZNPT material. Based on the numerical simulations, it is concluded that PZNPT can greatly improve the mechanical performance of the motor.