Digital image processing realized by memristor-based technologies.

Today performance and operational efficiency of computer systems on digital image processing are exacerbated owing to the increased complexity of image processing. It is also difficult for image processors based on complementary metal-oxide-semiconductor (CMOS) transistors to continuously increase the integration density, causing by their underlying physical restriction and economic costs. However, such obstacles can be eliminated by non-volatile resistive memory technologies (known as memristors), arising from their compacted area, speed, power consumption high efficiency, and in-memory computing capability. This review begins with presenting the image processing methods based on pure algorithm and conventional CMOS-based digital image processing strategies. Subsequently, current issues faced by digital image processing and the strategies adopted for overcoming these issues, are discussed. The state-of-the-art memristor technologies and their challenges in digital image processing applications are also introduced, such as memristor-based image compression, memristor-based edge and line detections, and voice and image recognition using memristors. This review finally envisages the prospects for successful implementation of memristor devices in digital image processing.

Post-exposure prophylaxis with SA58 (anti-SARS-COV-2 monoclonal antibody) nasal spray for the prevention of symptomatic COVID-19 in healthy adult workers: a randomized, single-blind, placebo-controlled clinical study.

Monoclonal antibodies (mAbs) and the post-exposure prophylaxis (PEP) with mAbs represent a very important public health strategy against coronavirus disease 2019 (COVID-19). This study has assessed a new Anti-SARS-COV-2 mAb (SA58) Nasal Spray for PEP against COVID-19 in healthy adults aged 18 years and older within three days of exposure to a SARS-CoV-2 infected individual. Recruited participants were randomized in a ratio of 3:1 to receive SA58 or placebo. Primary endpoints were laboratory-confirmed symptomatic COVID-19 within the study period. A total of 1222 participants were randomized and dosed (SA58, n = 901; placebo, n = 321). Median of follow-up was 2.25 and 2.79 days for SA58 and placebo, respectively. Adverse events occurred in 221 of 901 (25%) and 72 of 321 (22%) participants with SA58 and placebo, respectively. All adverse events were mild in severity. Laboratory-confirmed symptomatic COVID-19 developed in 7 of 824 participants (0.22 per 100 person-days) in the SA58 group vs. 14 of 299 (1.17 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 80.82% (95%CI 52.41%-92.27%). There were 32 SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) positives (1.04 per 100 person-days) in the SA58 group vs. 32 (2.80 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 61.83% (95%CI 37.50%-76.69%). A total of 21 RT-PCR positive samples were sequenced and all were the Omicron variant BF.7. In conclusion, SA58 Nasal Spray showed favourable efficacy and safety in preventing symptomatic COVID-19 or SARS-CoV-2 infection in adults who had exposure to SARS-CoV-2 within 72 h.

Fabrication of a bioconjugated dual-functional SERS probe for facile compound screening and detection.

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive technique for both detection and structural characterizations. To further exploit these advantages, we designed and fabricated a dual-functional SERS probe for specific capture and fast detection of small molecule ligands binding to target protein from a mixture of compounds such as extracts of natural products. As a proof of concept, we synthesized SiO2@Ag nanoclusters that are coated with 6-chlorohexanoic acid for covalent immobilization of serotonin transporter (5-HTT) fused with a Halo-tag through enzyme-substrate recognition. As such, we fabricated a bioconjugated SERS probe, and the synthesis, coating, protein immobilization, and affinity-based ligand binding have been characterized and verified by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and elemental mapping. By applying this probe to analyze Gardenia jasminoides extract, we have successfully identified crocin I as a compound binding to 5-HTT, which was further proved by using mass spectrometry (MS) and nuclear magnetic resonance (NMR). Taken together, we have developed a novel SERS probe by integrating the inherent strength of SERS in molecular analysis with an extended functionality of affinity-guided molecular capture, which has demonstrated the potential in drug screening of challenging systems.

Identification and validation of the model consisting of DDX49, EGFR, and T-stage as a possible risk factor for lymph node metastasis in patients with lung cancer.

INTRODUCTION: The lymph node metastasis stage of lung cancer is an important decisive factor in the need for postoperative adjuvant treatment and the difference between stage IIIa and stage IIIB that is the necessary information to distinguish whether surgery can be performed or not. The specificity of the clinical diagnosis of lung cancer with lymph node metastasis cannot meet the requirements of preoperative evaluation of surgical indications and prediction of surgical removal range in lung cancer. METHODS: This was an early experimental laboratory trial. The model identification data included the RNA sequence data of 10 patients from our clinical data and 188 patients with lung cancer from The Cancer Genome Atlas dataset. The model development and validation data consisted of RNA sequence data for 537 cases from the Gene Expression Omnibus dataset. We explore the predictive value of the model on two independent clinical data. RESULTS: A higher specificity of diagnostic model for patients with lung cancer with lymph node metastases consisted of DDX49, EGFR, and tumor stage (T-stage), which were the independent predictive factors. The area under the curve value, specificity, and sensitivity for predicting lymph node metastases were 0.835, 70.4%, and 78.9% at RNA expression level in the training group, and 0.681, 73.2%, and 75.7% at RNA expression level in the validation group as shown as in result part. To verify the predictive performance of the combined model for lymph node metastases, we downloaded the GSE30219 data set (n = 291) and the GSE31210 data set (n = 246) from the Gene Expression Omnibus (GEO) database as the training group and validation group, respectively. In addition, the model had a higher specificity for predicting lymph node metastases in independent tissue samples. CONCLUSIONS: Determination of DDX49, EGFR, and T-stage could form a novel prediction model to improve the diagnostic efficacy of lymph node metastasis in clinical application.

BDH1 promotes lung cancer cell proliferation and metastases by PARP1-mediated autophagy.

Lymph node metastases and distant metastases were the important limiting factor for therapy of unresectable locally advanced (IIIB stage) and oligotransduction (IVa stage) lung cancer. This study was undertaken to identify a novel predictive biomarker for predicting lymph node metastases of lung cancer. A total of 364 patients with lung cancer which comprised of 198 patients with transcriptome sequencing data, 110 cases with immunohistochemistry data and 66 patients with serum samples were included to identify and validate the candidate gene. Autophagy was measured by western blots, immunofluorescence and electron microscope. We found that 3-hydroxybutyrate dehydrogenase 1 (BDH1) was associated with proliferation and metastases of lung cancer. BDH1 expression in both tissue and serum samples was associated with lung cancer metastases. Mechanical studies revealed that the AMPK-mTOR signalling pathway mediated by PARP1 played an important role in BDH1-induced autophagy. Activation of mTOR pathway markedly increased the effect of BDH1 in cell proliferation and metastases. These results were verified by the knockdown of PARP1. Furthermore, in vivo administration of BDH1 effectively promoted tumour growth in H460 xenografts mice. Our finding not only suggested that BDH1 might be useful as a novel biomarker and therapeutic target for lung cancer metastases, but also imply that PARP1-mediated AMPK-mTOR signalling pathway might play a critical role in BDH1-induced autophagy and lung cancer proliferation and metastases.

DYRK2 downregulation in colorectal cancer leads to epithelial-mesenchymal transition induction and chemoresistance.

Colorectal cancer (CRC) is among the most prominent causes of cancer-associated mortality in the world, with chemoresistance representing one of the leading causes of treatment failure. However, the mechanisms governing such chemoresistance remain incompletely understood. In this study, the role of DYRK2 as a mediator of CRC cell drug resistance and the associated molecular mechanisms were assessed by evaluating human tumor tissue samples, CRC cell lines, and animal model systems. Initial analyses of The Cancer Genome Atlas database and clinical tissue microarrays revealed significant DYRK2 downregulation in CRC in a manner correlated with poor prognosis. We further generated LoVo CRC cells that were resistant to the chemotherapeutic drug 5-FU, and found that such chemoresistance was associated with the downregulation of DYRK2 and a more aggressive mesenchymal phenotype. When DYRK2 was overexpressed in these cells, their proliferative, migratory, and invasive activities were reduced and they were more prone to apoptotic death. DYRK2 overexpression was also associated with enhanced chemosensitivity and the inhibition of epithelial-mesenchymal transition (EMT) induction in these LoVo 5-FUR cells. Co-immunoprecipitation assays revealed that DYRK2 bound to Twist and promoted its proteasomal degradation. In vivo studies further confirmed that the overexpression of DYRK2 inhibited human CRC xenograft tumor growth with concomitant Twist downregulation. Overall, these results thus highlight DYRK2 as a promising therapeutic target in CRC worthy of further investigation.

Antiasthmatic Compounds Targeting ß2-Adrenergic Receptor from Perilla frutescens Improved Lung Inflammation by Inhibiting the NF-κB Signaling Pathway.

Asthma is a highly prevalent and heterogeneous chronic respiratory disease and is often treated with inhaled corticosteroids or in combination with a ß2-adrenergic receptor (ß2-AR) agonist. However, around 5% of asthma remains uncontrolled, and more effective antiasthmatic drugs with known mechanisms are in high demand. Herein, we immobilized ß2-AR on the polystyrene amino microsphere surface in a one-step fashion. The successful immobilization of ß2-AR was verified by scanning electron microscopy and chromatographic analysis. We screened rosmarinic acid (RA) as the bioactive compound targeting ß2-AR in Perilla frutescens (L.) Britton by mass spectroscopy. The binding constant between RA and ß2-AR was determined to be 2.95 × 104 M-1 by adsorption energy distribution and frontal analysis. The antiasthmatic effect and mechanism of RA were examined on a murine model of allergic asthma induced by ovalbumin (OVA) and aluminum hydroxide. The results showed that RA significantly reduced lung inflammatory cell numbers, the production of Th2 cytokines, and the secretion of total IgE, OVA-specific IgE, and eotaxin. The decreased inflammatory cell infiltration and mucus hypersecretion were associated with the inhibition of the NF-κB signaling pathway. Moreover, the mRNA expression levels of AMCase, CCL11, CCR3, Ym2, and E-selectin in the lung tissues were effectively reduced. It is the first time that RA was proven to target ß2-AR and be effective in counteracting allergic airway inflammation via the NF-κB signaling pathway. Therefore, the immobilized ß2-AR preserves the potential in screening antiasthmatic compounds from herbal medicine, and RA can be developed as an effective agent for the treatment of allergic asthma.

Lot-to-lot consistency, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults: A randomized, double-blind, phase IV trial.

Previous phase I to III clinical trials have shown that the inactivated SARS-CoV-2 vaccine namely CoronaVac has good efficacy, safety, and immunogenicity. This phase IV trial aims to evaluate the lot-to-lot consistency, immunogenicity, and safety on a commercial scale in healthy adults, which could provide data to support stable manufacturing. In this single-center, randomized, double-blind study, 1,080 healthy adults aged 26-45 years were randomly assigned into three groups to receive one of three lots of vaccines. All subjects received two doses of CoronaVac with an interval of 28 days. Serum samples were collected before the first dose and 28 days after the second dose to assess the immunogenicity. Solicited local and systemic adverse events (AEs) within 7 days and unsolicited AEs within 28 days after each dose of vaccination were recorded. A total of 1,039 participants completed the study and were included in the per-protocol set (PPS). The GMTs were 75.2 (68.5,82.6), 65.0 (59.0,71.7), and 65.3 (59.4,71.8), respectively, and the seroconversion rates of neutralizing antibody were all higher than 98%. The GMT ratios of each pair of lots were 1.16 (1.01,1.32), 1.15 (1.01, 1.32), and 0.99 (0.87, 1.14), respectively, meeting the immunological equivalence criteria. The incidence rates of adverse reactions (ARs) were 19.17%, 13.89%, and 18.33%, with no statistical difference. The ARs were all in grade 1 and grade 2, with incidences of 15.46% and 2.50%. Non-vaccine-related serious adverse events (SAEs) were reported. These results showed robust lot-to-lot consistency, immunogenicity, and safety. The stable production indicated that CoronaVac is suitable for large-scale use.Trial registration number: NCT04894227 (ClinicalTrials.gov).

Enhancing Chromatographic Performance of Immobilized Angiotensin II Type 1 Receptor by Strain-Promoted Alkyne Azide Cycloaddition through Genetically Encoded Unnatural Amino Acid.

During integration to the solid surface, the effects of tags introduced for bioorthogonal reactions on protein activity have received far less investigation. This represents the major challenge of improving the performance of the immobilized protein-based assays. Herein, the relationship between the fusion tags and their reaction efficiency in mediating the assay performance was realized by determining the chromatographic performance using genetically encoded azide-alkyne cycloaddition, and Halo- and SNAP-tagged bioorthogonal reactions for synthesizing immobilized angiotensin II type 1 receptor (AT1R). We demonstrated that immobilization with the incorporation of unnatural amino acid in the receptor minimizes the peak tailings and broadenings of irbesartan, fimasartan, losartan, and tasosartan, while attachment via large tags (SNAP and Halo) leads to serious asymmetry peaks. Upon the first immobilization, the association constants of the four drugs to AT1R appeared to be 1 order of magnitude greater than the other two attachments. Such enhancement is likely reasoned by the improved association rate constants and the relatively identical dissociation rates due to the small tag. While demonstrating improved chromatographic performance, the immobilized AT1R prepared by the genetically encoded azide-alkyne reaction was applied in analyzing Uncaria Schreber nom. cons. extract, which identified hynchophylline as a specific ligand binding to the receptor. As immobilized proteins move toward diverse assays, our findings provide an unprecedented insight into the relation between fusion tags and their reaction efficiency in mediating the assay performance, which is thus dedicated to the creation of a protein-functionalized surface for precisely determining the drug-protein interaction and discovering the specific partner of the protein.

Design of plasmonic enhanced all-optical phase-change memory for secondary storage applications.

Phase-change optical device has recently gained tremendous interest due to its ultra-fast transmitting speed, multiplexing and large bandwidth. However, majority of phase-change optical devices are only devoted to on-chip components such as optical tensor core and optical main memory, while developing a secondary storage memory in an optical manner is rarely reported. To address this issue, we propose a novel phase-change optical memory based on plasmonic resonance effects for secondary storage applications. Such design makes use of the plasmonic dimer nanoantenna to generate plasmonic resonance inside the chalcogenide alloy, and thus enables the performance improvements in terms of energy consumption and switching speed. It is found that choosing height, radius, and separation of the plasmonic nanoantenna as 10 nm, 150 nm, and 10 nm, respectively, allows for a write/erase energies of 100 and 240 pJ and a write/erase speed of 10 ns for crystallization and amorphization processes, respectively. Such performance merits encouragingly prevail conventional secondary storage memories and thus pave a route towards the advent of all-optical computer in near future.

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial.

BACKGROUND: A vaccine against SARS-CoV-2 for children and adolescents will play an important role in curbing the COVID-19 pandemic. Here we aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3-17 years. METHODS: We did a double-blind, randomised, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3-17 years old at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Individuals with SARS-CoV-2 exposure or infection history were excluded. Vaccine (in 0·5 mL aluminum hydroxide adjuvant) or aluminum hydroxide only (alum only, control) was given by intramuscular injection in two doses (day 0 and day 28). We did a phase 1 trial in 72 participants with an age de-escalation in three groups and dose-escalation in two blocks (1·5 µg or 3·0 µg per injection). Within each block, participants were randomly assigned (3:1) by means of block randomisation to receive CoronaVac or alum only. In phase 2, participants were randomly assigned (2:2:1) by means of block randomisation to receive either CoronaVac at 1·5 µg or 3·0 µg per dose, or alum only. All participants, investigators, and laboratory staff were masked to group allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint assessed in the per-protocol population was seroconversion rate of neutralising antibody to live SARS-CoV-2 at 28 days after the second injection. This study is ongoing and is registered with ClinicalTrials.gov, NCT04551547. FINDINGS: Between Oct 31, 2020, and Dec 2, 2020, 72 participants were enrolled in phase 1, and between Dec 12, 2020, and Dec 30, 2020, 480 participants were enrolled in phase 2. 550 participants received at least one dose of vaccine or alum only (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5 µg group, 63 (29%) of 217 in the 3·0 µg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p=0·55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1·5 µg group, 35 (16%) of 217 in the 3·0 µg group, and two (2%) in the alum-only group. As of June 12, 2021, only one serious adverse event of pneumonia has been reported in the alum-only group, which was considered unrelated to vaccination. In phase 1, seroconversion of neutralising antibody after the second dose was observed in 27 of 27 participants (100·0% [95% CI 87·2-100·0]) in the 1·5 µg group and 26 of 26 participants (100·0% [86·8-100·0]) in the 3·0 µg group, with the geometric mean titres of 55·0 (95% CI 38·9-77·9) and 117·4 (87·8-157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1-98·8]) in the 1·5 µg group and 180 of 180 participants (100·0% [98·0-100·0]) in the 3·0 µg group, with the geometric mean titres of 86·4 (73·9-101·0) and 142·2 (124·7-162·1). There were no detectable antibody responses in the alum-only groups. INTERPRETATION: CoronaVac was well tolerated and safe and induced humoral responses in children and adolescents aged 3-17 years. Neutralising antibody titres induced by the 3·0 µg dose were higher than those of the 1·5 µg dose. The results support the use of 3·0 µg dose with a two-immunisation schedule for further studies in children and adolescents. FUNDING: The Chinese National Key Research and Development Program and the Beijing Science and Technology Program.

ZEB1 promotes colorectal cancer cell invasion and disease progression by enhanced LOXL2 transcription.

Disease progression after curative surgery is still the main challenge for colorectal cancer (CRC). Identifying biomarkers and precise mechanisms in CRC disease progression is necessary for therapeutic improvement. As a transcription factor, ZEB1 promotes malignancy, but the precise mechanism by which ZEB1-dependent transcriptional regulation remains largely undefined. In this study, the transcriptional regulation of lysyl oxidase-like 2 (LOXL2) by ZEB1 in CRC was investigated. Our data show that ZEB1 enhanced LOXL2 transcription through direct binding to its promoter. The gain of function assays of ZEB1 showed increased cell proliferation, migration, and invasion. The inhibition of LOXL2 impaired the invasion and migratory ability of CRC cells, but had no effect on cell proliferation in vitro and in vivo. Immunohistochemical staining of tumor tissues indicated that elevated ZEB1/LOXL2 expression was significantly associated with lymph node metastasis and TNM stage. More importantly, elevated ZEB1/LOXL2 expression was an independent prognostic factor in CRC patients. These findings provide a molecular basis for the promotion of an invasive cancer phenotype by ZEB1-LOXL2 overexpression. Our results identify ZEB1/LOXL2 as a prognostic biomarker and potential therapeutic target against progression of CRC.

Fabrication and investigation of quaternary Ag-In-Zn-S quantum dots-based memristors with ultralow power and multiple resistive switching behaviors.

Quaternary Ag-In-Zn-S (AIZS) quantum dots (QDs) play critical roles in various applications since they have advantages of combining superior optical and electrical features, such as tunable fluorescence emission and high carrier mobilities. However, the application of semiconductor AIZS QDs in brain-inspired devices (e.g. memristor) has been rarely reported. In this work, the tunable volatile threshold switching (TS) and non-volatile memory switching (MS) behaviors have been obtained in a memristor composed of AIZS QDs by regulating the magnitude of compliance current. Additionally, the innovative Ag/AIZS structure devices without traditional oxide layer exhibit low operation voltage (∼0.25 V) and programming current (100 nA) under the TS mode. Moreover, the devices achieve reproducible bipolar resistive switching (RS) behaviors with large ON/OFF ratio of ∼105, ultralow power consumption of ∼10-10 W, and good device-to-device uniformity under the MS mode. Furthermore, the charge transport mechanisms of the high- and low-resistance states under the positive and negative bias have been analyzed with space-charge-limited-current and filament conduction models, respectively. This work not only validates the potential of AIZS QDs acting as dielectric layer in RS devices but also provides a new guideline for designing ultralow power and multiple RS characteristics devices.

Drip fertigation with straw incorporation significantly reduces N2O emission and N leaching while maintaining high vegetable yields in solar greenhouse production.

Approximately 1/3 of vegetables in China are produced in solar greenhouses. Most farmers use conventional irrigation with over fertilisation (CIF), thereby applying approximately 2000 kg N ha-1 fertiliser over two cropping seasons per year. Here, we tested the effect of drip irrigation with reduced fertilisation (DIF) combined with straw incorporation on reducing N2O emissions and nitrogen leaching from solar greenhouse vegetable production systems. Over three consecutive tomato cropping seasons, N2O emissions and nitrogen leaching were monitored in high temporal resolution, thereby producing a unique dataset. Compared to CIF, the realised drip fertigation scheme reduces N2O emission and nitrogen leaching of nitrate and dissolved organic nitrogen by approximately a factor of 5-10 (N2O-DIF: 10.3, CIF: 47.5 kg N ha-1 yr-1; N leaching-DIF: 83.6, CIF: 863 kg N ha-1 yr-1). Straw incorporation in CIF, though advantageous for soil health, resulted in pollution swapping as soil N2O emissions increased while NO3- leaching losses decreased. On the contrary, no significant negative environmental N effects of straw incorporation were found for DIF. As crop productivity was not affected by straw incorporation, neither for CIF nor for DIF, our study provides a sound basis for policy advice to recommend farmers to adopt drip fertigation combined with straw application. Wide scale adoption of this technique will result in reductions of environment N losses, alleviate major soil degradation signs, including soil acidity, nutrient imbalance and deterioration of soil microbial community structure, while allowing to maintaining high yields of vegetables in solar greenhouse production systems.

Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer.

Resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has become the main clinical challenge of advanced lung cancer. This research aimed to explore the role of PARP1-mediated autophagy in the progression of TKI therapy. PARP1-mediated autophagy was evaluated in vitro by CCK-8 assay, clonogenic assay, immunofluorescence, and western blot in the HCC-827, H1975, and H1299 cells treated with icotinib (Ico), rapamycin, and AZD2281 (olaparib) alone or in combination. Our results and GEO dataset analysis confirmed that PARP1 is expressed at lower levels in TKI-sensitive cells than in TKI-resistant cells. Low PARP1 expression and high p62 expression were associated with good outcomes among patients with NSCLC after TKI therapy. AZD2281 and a lysosomal inhibitor reversed resistance to Ico by decreasing PARP1 and LC3 in cells, but an mTOR inhibitor did not decrease Ico resistance. The combination of AZD2281 and Ico exerted a markedly enhanced antitumor effect by reducing PARP1 expression and autophagy in vivo. Knockdown of PARP1 expression reversed the resistance to TKI by the mTOR/Akt/autophagy pathway in HCC-827IR, H1975, and H1299 cells. PARP1-mediated autophagy is a key pathway for TKI resistance in NSCLC cells that participates in the resistance to TKIs. Olaparib may serve as a novel method to overcome the resistance to TKIs.

Ellagic acid inhibits cell proliferation, migration, and invasion in melanoma via EGFR pathway.

Ellagic acid (EA), a polyphenolic compound from pomegranate fruit extracts, has been reported to possess anti-proliferation, pro-apoptosis, and anti-invasion effects on many cancers. However, its effect on melanoma is yet to be clarified. In the present study, we investigated the anti-cancer effects of EA on melanoma cells in vitro and in vivo. The results indicated that 40 µM of EA significantly inhibited the proliferation, migration, and invasion of WM115 and A375 cells. The EA treatment significantly decreased the expression of p-EGFR and Vimentin, but increased the expression of E-cadherin in both cell lines. We further found that EGFR activation significantly abolished the effect of EA on WM115 and A375 cells. Moreover, EA treatment impaired in vivo tumorigenesis of A375 cells. Moreover, elevated pEGFR expression was an independent detrimental factor for melanoma patients. Taken together, our study provided evidence that EA treatment inhibits the migration, invasion and proliferation of melanoma cells via EGFR signaling pathway. These findings strongly suggested that EA might be useful for the development of new therapeutic strategies at melanoma.

DDX49 is a novel biomarker and therapeutic target for lung cancer metastases.

The identification of lymph node metastases is important for the diagnosis, treatment and prognosis of patients with lung cancer. We found DDX49 was associated with the lymph node metastases in lung cancer by the Akt/ß-catenin pathway. Transcriptome sequencing, bioinformatics analysis, quantitative RT-PCR, cell transfection and the Cancer Genome Atlas (TCGA) data set were used to identify DDX49 responsible for lymph node metastases. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to explore the possible molecular mechanism in experimental cell. The DDX49 gene was correlated significantly with lymph node metastases of lung cancer. The knockdown of DDX49 inhibited the cell proliferation and migration in PC-9 and H460 cells. The mechanism research found downexpression of DDX49 decreased the Akt/ß-catenin pathway in lung cancer cell. In vivo experiments showed that DDX49 promoted the proliferation and metastases of lung cancer cells by increasing the Akt/ß-catenin pathway. These findings suggested that DDX49 may be useful as a novel biomarker of lymph node metastases and therapeutic target for lung cancer metastasis.

Prognostic role of upregulated P300 expression in human cancers: A clinical study of synovial sarcoma and a meta-analysis.

E1A binding protein p300 (P300) is a member of the histone acetyltransferase family of transcriptional co-activators, which are associated with various types of cancer. Numerous studies have evaluated the diagnostic value of P300, but their results are not consistent. Therefore, a clinical study and a meta-analysis were performed in the present study to investigate the prognostic value of P300 expression in human malignant neoplasms. Immunohistochemical (IHC) analysis was used to assess P300 expression in 43 paraffin-embedded primary synovial sarcoma (SS) samples. For the meta-analysis, eligible studies published until January 21, 2018 were identified by searching the PubMed, EMBASE and Web of Science databases. The IHC analysis indicated a high P300 expression rate in 33.3% (10/30) of biphasic SS (BSSs) and in 60% (6/10) of monophasic fibrous SS tissues. In BSS, the expression rate was significantly higher in the epithelial component (80.0%, 24/30) than that in the spindle-cell component (30.0%, 9/30; P<0.05). The meta-analysis indicated that high expression of P300 was associated with poor overall survival (OS) in digestive system malignant neoplasms (HR=1.54, 95% CI: 1.20-2.23), as well as with poor progression-free survival, recurrence-free survival and disease-free survival combined (HR=1.84, 95% CI: 1.36-2.47). Analysis of subgroups by ethnicity demonstrated that high expression of P300 was associated with poor OS in Asians (HR=1.72, 95% CI: 1.20-2.47) but favourable OS in Caucasians (HR=0.59, 95% CI: 0.47-0.73). Furthermore, high expression of P300 was associated with clinical stage [Relative Risk (RR)=1.30, 95% CI: 1.07-1.58], lymph node metastasis (RR=1.30, 95% CI: 1.03-1.64) and depth of invasion (RR=1.31, 95% CI: 1.07-1.60). P300 expression may therefore be a useful biomarker for predicting patient prognosis in various types of human cancer.

Resistance Switching Statistics and Mechanisms of Pt Dispersed Silicon Oxide-Based Memristors.

Silicon oxide-based memristors have been extensively studied due to their compatibility with the dominant silicon complementary metal-oxide-semiconductor (CMOS) fabrication technology. However, the variability of resistance switching (RS) parameters is one of the major challenges for commercialization applications. Owing to the filamentary nature of most RS devices, the variability of RS parameters can be reduced by doping in the RS region, where conductive filaments (CFs) can grow along the locations of impurities. In this work, we have successfully obtained RS characteristics in Pt dispersed silicon oxide-based memristors. The RS variabilities and mechanisms have been analyzed by screening the statistical data into different resistance ranges, and the distributions are shown to be compatible with a Weibull distribution. Additionally, a quantum points contact (QPC) model has been validated to account for the conductive mechanism and further sheds light on the evolution of the CFs during RS processes.

Drip fertigation significantly reduces nitrogen leaching in solar greenhouse vegetable production system.

Vegetable production in solar greenhouses in northern China results in the excessive use of nitrogen (N) fertilizers and water via flooding irrigation. Both factors result in low N use efficiency and high environmental costs because groundwater becomes contaminated with nitrate (NO3-). Four consecutive tomato (Lycopersicum esculentum Mill.) cropping seasons were tested whether drip fertigation and/or the incorporation of maize straw (S) may significantly reduce NO3- and dissolved organic N (DON) leaching while increasing the water-use efficiency (WUE) and partial factor productivity of applied N (PFPN) of the tomatoes. The following treatments were used: ① conventional flooding irrigation with overfertilization (CIF, 900 kg N ha-1 season-1), ② CIF + S, ③ drip irrigation with optimized fertilization (DIF, 400 kg N ha-1 season-1), ④ DIF + S. We found that (1) DIF significantly increases the PFPN and WUE by 262% and 73% without compromising the yield compared with CIF, respectively. (2) For CIF, approximately 50% of the total N input was leached at a NO3-/DON ratio of approximately 2:1. (3) Compared with CIF, DIF reduced NO3- and DON leaching by 88% and 90%, respectively. Water percolation was positively correlated with N leaching (p < 0.001). (4) Straw application only reduced NO3- leaching losses in the first year and did not affect DON leaching overall, although DON leaching was increased in DIF in the first growing season. In conclusion, DIF significantly reduces NO3- and DON leaching losses by approximately 90% compared with the current farmer practice (CIF). Considering the significant DON leaching losses, which have been overlooked because previous measurements focused on NO3-, DON should be considered as a primary factor of environmental pollution in conventional solar greenhouse vegetable production systems.