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To study the material basis and mechanism of volatile oil from Alpinia oxyphylla in treating Alzheimer's disease(AD) based on GC-MS and network pharmacology. Ingredients of volatile oil from A.oxyphylla were analyzed by GC-MS. Targets of those ingredients were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Relevant targets of AD were obtained through such databases as DrugBank, STITCH, OMIM. Intersection targets of ingredients and diseases were obtained by Online Venny map, and PPI network was established by STRING to screen out core targets. Gene ontology(GO) functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID. Thequot;ingredients-target-pathwayquot; network was constructed by software Cytoscape 3.8.1 to screen out potential active ingredients of volatile oil from A.oxyphylla in the treatment of AD. The results showed that a total of 6 active ingredients were screened from the volatile oil of A.oxyphylla by GC-MS, 17 targets corresponding to 6 active ingredients were found in TCMSP database, and 3 448 AD targets were found in DrugBank database.quot;Ingredients-target-pathwayquot; network and PPI network showed there were 4 potential active ingredients in the treatment of AD and 4 core targets. GO analysis and KEGG analysis showed 34(Plt;0.05) and 5(Plt;0.05) pathways, respectively, including nerve ligand receptor interaction, calcium signaling pathway, cholinergic synapse and 5-hydroxytryptaminergic synapse. This suggested that volatile oil from A.oxyphylla could synergistically treat AD by regulating calcium balance, cholinergic balance and phosphorylation. This study provided reference and guidance for further study of volatile oil from A.oxyphylla in the treatment of AD.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck, and radiotherapy is the main approach for this disease, while irradiation resistance is a huge challenge that influences radiosensitivity. This study aims to determine the role and function of miR-29a-3p and ADAM12 in the radiosensitivity of OSCC cells. The expression pattern of ADAM12 in OSCC cells was searched in TCGA database. The binding of miR-29a-3p and ADAM12 was predicted by Starbase and verified using dual luciferase reporter gene assay. The RNA or protein expressions of miR-29a-3p and ADAM12 were measured by RT-qPCR or western blot. OSCC cell lines were treated by various γ-ray irradiation dosages before the alteration on miR-29a-3p expression and on the cell viability, proliferation, migration and cell apoptosis was detected. ADAM12 was highly expressed in OSCC cells, whose expression in resistant cells was positively correlated with irradiation dosage. Overexpression of ADAM12 in OSCC cells lead to increased cell proliferation and migration ability as well as inhibited cell apoptosis. miRNAs potentially binding ADAM12 in PITA, microT, miRmap and targetscan were screened, among which miR-29a-3p had the maximum differential expression levels in OSCC cells determined by RT-qPCR. Overexpression of miR-29a-3p resulted in suppressed cell viability, proliferation, migration ability and increased cell apoptosis, while this expression pattern can be partially counteracted by ADAM12 overexpression in OSCC cells. miR-29a-3p through targeting and inhibiting AMDM12 enhances the radiosensitivity of OSCC cells.

Background Endoscopy biopsy (EB) is the standard diagnostic method for colorectal cancer (CRC), whereas its accuracy and efficiency in mucinous adenocarcinoma (MAC) initial diagnosis is unclear. Methods The initial EB and postoperative specimen (PS) pathological diagnosis of MAC from two centers were retrospectively collected and analyzed. The accuracy and efficiency of initial EB compared with PS pathological diagnosis were analyzed. The potential factors which would affect the initial EB diagnosis of MAC were analyzed. Results 280 and 78 eligible cases were enrolled in this study from two centers respectively. The initial EB diagnosis accuracy for MAC were 84.62% and 83.33%. However, among the cases of PS diagnosis with MAC, the diagnostic efficiency of initial EB was only 36.49% and 32.50% respectively. Lower tumor differentiation and more EB number were associated with an increased probability for the EB diagnosis of MAC, but only tumor differentiation was an independent diagnositic factor for EB in the two cohorts. Conclusions The accuracy of initial EB with MAC is high, but the diagnostic efficiency was extremely low. Tumor differentiation and EB number were associated with the diagnosis efficiency of MAC before surgery.

Despite the benefits of global coverage with high spatiotemporal resolutions, satellite precipitation products (SPPs) still suffer from inadequate accuracy in natural hazard forecasts, hydrology, and water resources management. Rain/no-rain (R/NR) detection error significantly affects the accuracy of daily SPPs, which has attracted increasing attention in recent years. This paper proposed a precipitation bias correction framework (PBCF) to improve the accuracy of daily SPPs, focusing on improving the ability of SPPs to detect the occurrence of the precipitation based on a R/NR discrimination model. Multiple land and climate variables derived from ERA5-Land reanalysis dataset were used to construct the R/NR discrimination model using the artificial neural network (ANN) method. A case study on the bias correction of daily precipitation of Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (GPM) mission (IMERG) over Hanjiang River Basin (HRB) was conducted for the period 2004–2018. Daily precipitation of 64 meteorological stations in HRB were spatially and randomly divided into two groups: 44 stations were used for training, validating and testing the constructed R/NR discrimination model, and the other 20 stations were used to evaluate the performance of the R/NR discrimination model in different topographic areas. The results indicate that the proposed PBCF could reduce the bias of IMERG, with the correlation coefficient (R) increased by 19.4%, the root mean square error (RMSE) and the mean absolute error (MAE) decreased by 19.0% and 29.9% on the daily scale, respectively. The constructed R/NR discrimination model could improve the ability of IMERG for detecting the precipitation occurrence, with a classification accuracy of about 86.5% and the equitable threat score (ETS) increased from 0.15 to 0.58. Further analyses showed that the proposed PBCF was more efficient than the cumulative distribution function mapping method in correcting IMERG. This study provides a novel insight for the correction of daily SPPs.

Aiming at the accuracy of network resource recommendation, the complex behavior of network users is studied. Through front-end embedded JS code and Java Web Framework custom filter, multi-data sources acquisition is realized, and the data acquisition is preprocessed. The complex behavior is normalized by entropy weight method. Flume+Kafka+Hbase are used to provide reliable high-speed storage and query, and the complex behavior of network users is obtained, which is precisely recommended for network resources. The proposed method is reliable and fast serviced. This complex behavior analysis method is applied to the network resources recommendation system. The system supports multi-channel rapid and stable acquisition, million-level data reliable storage, and millisecond query speed, which greatly improves the real-time and accuracy of complex behavior network resource recommendation under the condition that the business logic remains unchanged.

In recent years, denoising methods based on deep learning have achieved unparalleled performance at the cost of large computational complexity. In this work, we propose an Efficient Multi-stage Video Denoising algorithm, called EMVD, to drastically reduce the complexity while maintaining or even improving the performance. First, a fusion stage reduces the noise through a recursive combination of all past frames in the video. Then, a denoising stage removes the noise in the fused frame. Finally, a refinement stage restores the missing high frequency in the denoised frame. All stages operate on a transform-domain representation obtained by learnable and invertible linear operators which simultaneously increase accuracy and decrease complexity of the model. A single loss on the final output is sufficient for successful convergence, hence making EMVD easy to train. Experiments on real raw data demonstrate that EMVD outperforms the state of the art when complexity is constrained, and even remains competitive against methods whose complexities are several orders of magnitude higher. Further, the low complexity and memory requirements of EMVD enable real-time video denoising on commercial SoC in mobile devices.

Image denoising is one of the most critical problems in mobile photo processing. While many solutions have been proposed for this task, they are usually working with synthetic data and are too computationally expensive to run on mobile devices. To address this problem, we introduce the first Mobile AI challenge, where the target is to develop an end-to-end deep learning-based image denoising solution that can demonstrate high efficiency on smartphone GPUs. For this, the participants were provided with a novel large-scale dataset consisting of noisy-clean image pairs captured in the wild. The runtime of all models was evaluated on the Samsung Exynos 2100 chipset with a powerful Mali GPU capable of accelerating floating-point and quantized neural networks. The proposed solutions are fully compatible with any mobile GPU and are capable of processing 480p resolution images under 40-80 ms while achieving high fidelity results. A detailed description of all models developed in the challenge is provided in this paper., Mobile AI 2021 Workshop and Challenges: https://ai-benchmark.com/workshops/mai/2021/. arXiv admin note: substantial text overlap with arXiv:2105.07809, arXiv:2105.07825

In order to reduce the blocking rate of wavelength routing DWDM optical network and improve the wavelength resource utilization, this paper proposes a deep learning optical network routing algorithm based on wavelength continuity supervision (DL-RWA). In this algorithm, wavelength continuity is taken as the key parameter, and the data set is created by supervised learning. After the deep neural network (DNN) is constructed, the data set is used to train it, and the network parameters are adjusted, so that the algorithm can select the routing and wavelength assignment (RWA) scheme with the best wavelength continuity according to the real-time situation of the dynamic network. The simulation results show that compared with the traditional KSP + FF routing algorithm, DL-RWA algorithm can effectively enhance the routing effect and improve the network environment when dealing with the long correlation traffic model (IP traffic simulation).

[Image: see text] The intracellular delivery of biomolecules is of significant importance yet challenging. In addition to the conventional delivery of nanomaterials that rely on biochemical pathways, vertical nanowires have been recently proposed to physically penetrate the cell membrane, thus enabling the direct release of biomolecules into the cytoplasm circumventing endosomal routes. However, due to the inherent attachment of the nanowires to a planar 2D substrate, nanowire cell penetrations are restricted to in vitro applications, and they are incapable of providing solution-based delivery. To overcome this structural limitation, we created polyethylenimine-functionalized microparticles covered with nanospikes, namely, “spiky particles”, to deliver biomolecules by utilizing the nanospikes to penetrate the cell membrane. The nanospikes might penetrate the cell membrane during particle engulfment, and this enables the bound biomolecules to be released directly into the cytosol. TiO(2) spiky particles were fabricated through hydrothermal routes, and they were demonstrated to be biocompatible with HeLa cells, macrophage-like RAW cells, and fibroblast-like 3T3-L1 cells. The polyethylenimine-functionalized spiky particles provided direct delivery of fluorescent siRNA into cell cytosol and functional siRNA for gene knockdown as well as successful DNA plasmid transfection which were difficult to achieve by using microparticles without nanospikes. The spiky particles presented a unique direct cell membrane penetrant vehicle to introduce biomolecules into cell cytosol, where the biomolecules might bypass conventional endocytic degradation routes.

Detection of H2O2 in bio-fluids plays an important role in early-diagnosis of many diseases, and thus the development of electrochemical H2O2 sensors has been explored. However, constructing robust sensors that could self-clean and avoid biofouling is still challenging, because the complex compositions of bio-fluids could easily absorb to or even passivate the sensor electrode. In this work, we reported the development of H2O2 electrochemical sensor based on hierarchical vertical graphene/nanorods structure (vG/NRs) with self-cleaning and anti-biofouling properties. The hierarchical vG/NRs structure consisted of ZnO nanorods branched on vertical graphene nanowalls, which were fabricated through multiple steps of plasma enhanced chemical vapor deposition, atomic layer deposition and hydrothermal growth. The hierarchical vG/NRs after fluorination (vG/NRs-F) displayed excellent liquid repellence and anti-platelet adhesion properties. The vG/NRs-F was utilized as working electrodes and integrated as electrochemical sensors. H2O2 molecules in solution could access to the vG/NRs surface, inducing electrochemical signals for detection with reasonable sensitivity and selectivity. Meanwhile, the vG/NRs-F electrode could resist the contamination of biocomponents in blood serum after sensing experiment, enabling stable sensing of H2O2 without interfering by biofouling. Our work offers a promising strategy to design self-cleaning and anti-biofouling sensors with extended applicability for detection in complex biological fluids.

Injectable micron-sized particles have historically achieved promising applications, but they continued to suffer from long-term biofouling caused by the adhesions of biomolecules, cells, and bacteria. Recently, a slippery lubricant infusion porous substrate (SLIPS) exhibited robust antiadhesiveness against many liquids; however, they were constructed using a 2D substrate, and they were not suitable for in vivo applications, such as injectable biomaterials. Inspired by SLIPS, here, we report the first case of injectable solid microparticles coated with a lubricating liquid surface to continuously resist biofouling. In our design, microparticles were attached with nanospikes and fluorinated to entrap the lubricant. The nanospikes enabled the lubricant-coated spiky microparticles (LCSMPs) to anomalously disperse in water despite the attraction between the surfaces of the microparticles. This result indicated that the LCSMPs exhibited persistent anomalous dispersity in water while maintaining a robust lubricating surface layer. LCSMPs prevented the adhesion of proteins, mammalian cells, and bacteria, including Escherichia coli and Staphylococcus aureus. LCSMPs also reduced in vivo fibrosis while conventional microparticles were heavily biofouled. This technology introduced a new class of injectable anti-biofouling microparticles with reduced risks of inflammation and infections., We fabricated microparticles with nanospikes and functionalized the surface to entrap lubricant. The microparticles displayed robust and persistent anti-biofouling properties.

6063 Background: We hypothesized that concurrent chemoradiotherapy (CCRT) plus concurrent and adjuvant camrelizumab as first-line treatmentwas associated with improved survival compared with concurrent chemoradiotherapy alone for nonoperative locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The purpose of this comparative study was to compare the efficacy and toxicity of CCRT plus concurrent and adjuvant camrelizumab versus CCRT alone in nonoperative locoregionally advanced HNSCC. Methods: One hundred and eighty patients with nonoperative locoregionally advanced HNSCC (cancer of the oral cavity, oropharyngeal cancer, hypopharyngeal cancer and laryngeal cancer) received either CCRT plus concurrent and adjuvant camrelizumab (camrelizumab + CCRT group, n = 90) or CCRT alone (CCRT alone group, n = 90). Patients in both groups received curative cisplatin-based concurrent chemoradiotherapy. The radiation dose was 70 Gy (2.0 Gy/fraction). In camrelizumab + CCRT group, concurrent camrelizumab (200mg/day on days 1, 22, 43) was added to CCRT, followed by adjuvant camrelizumab (200mg, every 3 weeks for 6 months or until disease progression, unacceptable adverse events or withdrawal of consent). Results: Compared with CCRT alone, the addition of concurrent and adjuvant camrelizumab significantly improved complete response (CR) rates (92.2% vs. 80.0%; P = 0.018), 3-year disease free survival (DFS, 72.2% vs. 56.7%; P = 0.029), locoregional recurrence-free survival (LRRFS, 76.7% vs. 61.1%; P = 0.024), and overall survival (OS, 78.9% vs. 63.3%; P = 0.033). Reactive cutaneous capillary endothelial proliferation was higher in the camrelizumab + CCRT group (6.7% vs. 0.0%; P = 0.013). No statistically significant differences in other acute (mucositis, leukopenia, thrombocytopenia, anemia, etc.) and late toxic effects (mucosal necrosis, trismus, cranial nerve palsy, etc.) were observed between the two groups. The addition of camrelizumab (CCRT plus camrelizumab vs. CCRT alone) was a significant independent prognostic factor for 3-year DFS, LRRFS and OS (P = 0.038, P = 0.032, and P = 0.048, respectively). Conclusions: Concurrent chemoradiotherapy plus concurrent and adjuvant camrelizumab as first-line treatment is associated with a considerable survival benefit, with acceptable adverse events, as compared with concurrent chemoradiotherapy alone, among patients with nonoperative locoregionally advanced head and neck squamous cell carcinoma. Our ongoing prospective clinical trial (registered with chictr.org.cn, number ChiCTR2200056298) will further investigate the efficacy of camrelizumab in combination with chemoradiotherapy for HNSCC.

Solar-driven electrochemical CO2 reduction to fuels has considerable potential to satisfy future renewable energy needs and mitigate CO2 emissions, but current approaches face significant challenges, such as poor selectivity and large overpotential for the catalytic reactions. Here we present a hybrid microbial-photoelectrochemical system that selectively converts CO2 into methane in a single step without any by-products. The hybrid system employs a biocathode that was capable of reducing CO2 into CH4 with an unprecedentedly low overpotential (

Microbial biochemicals have been indicated as the primary stimulators of innate immunity, the first line of the body’s defence against infections. However, the influence of topological features on a microbe’s surface on immune responses remains largely unknown. Here we demonstrate the ability of TiO2 microparticles decorated with nanospikes (spiky particles) to activate and amplify the immune response in vitro and in vivo. The nanospikes exert mechanical stress on the cells, which results in potassium efflux and inflammasome activation in macrophages and dendritic cells during phagocytosis. The spiky particles augment antigen-specific humoral and cellular immune responses in the presence of monophosphoryl lipid A and elicit protective immunity against tumour growth and influenza viral infection. The study offers insights into how surface physical cues can tune the activation of innate immunity and provides a basis for engineering particles with increased immunogenicity and adjuvanticity.

Background Metastasis is the main cause of death in patients with advanced stage colon cancer. Epithelial mesenchymal transition (EMT) plays an important role in invasion and metastasis. Actin-like 6A (ACTL6A) is vital for embryogenesis and differentiation and is also critical for metastasis and EMT in hepatocellular carcinoma, as observed in our previous study. In the present study, we further explored the role of ACTL6A in colon cancer metastasis. Methods ACTL6A expression levels were analyzed in normal colon, colon adenoma and colon cancer specimens using public databases and tissue samples. ACTL6A expression and its association with clinicopathologic features of colon cancer patients were also analyzed. ACTL6A-overexpression and ACTL6A-knockdown colon cancer cells were used to perform cytological experiments to explore the potential biological function of ACTL6A in metastasis and EMT in colon cancer. Results The data from both the Gene Expression Omnibus (GEO) and Oncomine databases showed that ACTL6A expression levels in colon adenoma and cancer were higher than those in normal colon samples. The ACTL6A expression level in fresh colon cancer specimens was also higher than that in the corresponding adjacent normal colon specimens. Patients with high ACTL6A expression directly correlated with advanced pT status, distant metastasis, poor differentiation and microvascular/perineural invasion. ACTL6A overexpression promoted migration and invasion of colon cancer cells, whereas ACTL6A knockdown exhibited the opposite effect in vitro. Moreover, we demonstrated that ACTL6A promoted EMT in colon cancer cells in vitro. Conclusions Our findings indicate that ACTL6A exhibits pro-tumor function and acts as an EMT activator in colon cancer. ACTL6A may serve as a potential therapeutic target for colon cancer. Electronic supplementary material The online version of this article (10.1186/s12885-018-4931-3) contains supplementary material, which is available to authorized users.

With the increase of the renewable energy sources connected to the power system, the fluctuation and uncertainty of the output of the renewable energy generator has significant effects on power system security and stability operation. The synchronicity of power generation characteristics and load demands are different, which leads to frequency regulation pressure of power system further prominent. The battery energy storage system has good frequency regulation ability and can quickly respond to system frequency change. In this paper, in the case of the energy storage required to be configured in new wind farms, the virtual inertia control, and droop control strategies of energy storage participating in frequency regulation are proposed. Then, the comprehensive control strategy is put forward, considering the frequency regulation ability of the wind turbines and energy storage system. Finally, the effectiveness of the proposed control strategy is verified by using the IEEE 30-bus system.

This paper reviews the first NTIRE challenge on quality enhancement of compressed video, with a focus on the proposed methods and results. In this challenge, the new Large-scale Diverse Video (LDV) dataset is employed. The challenge has three tracks. Tracks 1 and 2 aim at enhancing the videos compressed by HEVC at a fixed QP, while Track 3 is designed for enhancing the videos compressed by x265 at a fixed bit-rate. Besides, the quality enhancement of Tracks 1 and 3 targets at improving the fidelity (PSNR), and Track 2 targets at enhancing the perceptual quality. The three tracks totally attract 482 registrations. In the test phase, 12 teams, 8 teams and 11 teams submitted the final results of Tracks 1, 2 and 3, respectively. The proposed methods and solutions gauge the state-of-the-art of video quality enhancement. The homepage of the challenge: https://github.com/RenYang-home/NTIRE21_VEnh, Comment: Corrected the MOS values in Table 2, and corrected some minor typos

Subtilisin NAT, a Bacillus subtilisin, is widely applied as a functional food and considered to be one of the most exploitable potential oral thrombolytic agents. Subtilisin QK, another Bacillus subtilisin, is a serine protease fermented by Bacillus subtilis 02 and has a better thrombolytic effect. Therefore, subtilisin QK is typically used for evaluating the safety of Bacillus subtilisins. Here, we conduct several good laboratory practice (GLP)-compliant studies in non-rodent animal, i.e., in Beagle dogs, including acute toxicity, subchronic toxicity, and safety pharmacology studies. No adverse effects were evident in the acute and 28-d subchronic toxicity studies at doses up to 40000 FU/kg and 16000 FU/kg/d, respectively. In evaluating the pharmacological safety of up to 2000FU/kg subtilisin QK, we found no significant differences between the electrocardiograms, blood pressures, and respiration of beagle dogs. These findings suggest the safety of Bacillus subtilisin, providing reliable pharmacological and toxicological data for its development and popularization as a functional food and drug.

With the high penetration of renewable energy sources participating in the power grid, frequency stability control becomes a significant problem restricting the security and stability operation of a multi-HVDC sending-end system with a small load and large power. HVDC monopolar blocking or bipolar blocking leads to increasing the sending-end system frequency. Over-frequency generator tripping is an important control measure to restraining the sending-end system frequency increasing. This paper proposes the configuration principles of over-frequency generator tripping considering the transient instability generating units, the frequency protection of wind turbines, and the variation of the line power flow. Then, the configuration process and the method of the over-frequency generator tripping scheme is proposed according to the configuration principles and the field operation experience. An example of a provincial power grid is used to verify the effectiveness and the adaptability of the proposed over-frequency generators tripping scheme under different operation modes and HVDC blocking failures.

With the rapid development of urban agglomerations, urban water use and wastewater environments have gradually constrained sustainable development and caused increasing concern. In this paper, we selected the urban agglomeration on the middle reaches of the Yangtze River (UAMRYZ) as a typical area. We proposed an integrated urban water use and wastewater treatment (UWUWT) system and its urban water use (UWU) subsystem and urban wastewater treatment (UWT) subsystem. Moreover, an integrated two-stage slacks-based measure (SBM) data envelopment analysis (DEA) model was used to evaluate the efficiency of the UWUWT system and its subsystem during 2010 to 2017. Additionally, the multiscale geographically weighted regression (MGWR) model was adopted to analyze the influence mechanism of each factor on the defined system. The results indicated that the tendency of UWU efficiency and UWUWT efficiency were similar and mainly showed the same trend with an ‘N’ shape in a time-dependent manner for the UAMRYZ and provinces, respectively. Furthermore, the UWU efficiency and UWUWT efficiency of each city showed strong spatiotemporal heterogeneity. The UWT efficiency of the UAMRYZ and its representative cities was stable in the region and always had a higher value. With continuous economic development and increased interregional foreign trade, the UWU subsystem efficiency and the UWUWT system efficiency had a significant increase for cities along the entire river in the Yangtze Basin. The regional differences of the overall UWU efficiency, UWT efficiency and UWUWT efficiency gradually decreased and the efficiency has gradually improved from 2010 to 2017. Attribution analysis showed that the secondary industry was the main constraining factor, while the water resource was the most acceleration factor for the UWUWT system in most areas and the UWT subsystem for all cities. Our study evaluated the specific insufficiencies of the defined system and supported regulatory policies.

Background This study aims to investigate the mechanism underlying the high level of long non-coding RNA FOXD3-AS1 in cisplatin-resistant NSCLC cells. Methods Cisplatin-resistant cells were generated from A549 cells. CCK-8 were used to evaluate cell proliferation. The FOXD3-AS1, miR-127-3p, MDM2 and MRP1 mRNA expression levels were confirmed by qRT-PCR. Protein levels of MDM2 and MRP1 were determined by western blot assay. Luciferase reporter and RNA pull-down assays were evaluated the relationship between miR-127-3p and FOXD3-AS1/MDM2. In vivo tumor growth was evaluated in a xenograft nude mice model. Results FOXD3-AS1 was up-regulated in cisplatin-resistant NSCLC cells (A549/DDP and H1299/DDP cells) in comparison with their parental cell lines. Overexpression of FOXD3-AS1 promoted cisplatin-resistance in A549 and H1299 cells; while FOXD3-AS1 knockdown sensitized A549/DDP and H1299/DDP cells to cisplatin treatment. FOXD3-AS1 regulated miR-127-3p expression by acting as a competing endogenous RNA, and miR-127-3p repressed MDM2 expression via targeting the 3′UTR. MiR-127-3p overexpression and MDM2 knockdown both increased the chemo-sensitivity in A549/DDP cells; while miR-127-3p knockdown and MDM2 overexpression both promoted chemoresistance in A549 cells. Further rescue experiments revealed that miR-127-3p knockdown or MDM2 overexpression counteracted the suppressive effects of FOXD3-AS1 knockdown on chemo-resistance and MRP1 expression in A549/DDP cells. In vivo studies showed that FOXD3-AS1 knockdown potentiated the antitumor effects of cisplatin treatment. Inspection of clinical samples showed the upregulation of FOXD3-AS1 and MDM2, and down-regulation of miR-127-3p in NSCLC tissues compared to normal adjacent tissues. Conclusion In conclusion, our results suggest that LncRNA FOXD3-AS1 promotes chemo-resistance of NSCLC cells via directly acting on miR-127-3p/MDM2 axis. Our findings may provide novel perspectives for the treatment of NSCLC in patients resistant to chemotherapy.

According to traditional Chinese medicine,quot;spleen transportquot; is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.

Ethnopharmacological relevance Traditional Chinese medicine believes that depression syndrome has become one of the core pathogenesis of insomnia. The pharmacology of traditional Chinese medicine points out that Perilla frutescens has the effect of regulating Qi and relieving depression, promoting Qi circulation to relieve pain, so Perilla frutescens may have the potential therapeutic effect on insomnia. Related studies have reported the sedative and hypnotic effects of Perilla frutescens, but these studies have not yet explored the mechanism of sedative and hypnotic effects of Perilla frutescens essential oil (PFEO) through inhalation administration. Aim of the study The purpose of this study is to explore the underlying sedative and hypnotic mechanisms of PFEO through the GABAergic system pathways. Materials and methods Established the PCPA insomnia model of mice, The open field test, pentobarbital-induced falling asleep rate, latency of sleeping time, and duration of sleeping time experiments were used to evaluate the behavior of mice, the enzyme-linked immunosorbent assay was used to analyze the content of 5-HT and GABA in hypothalamus and cerebral cortex. Immunohistochemical experiment, Western blot experiment and RT-PCR experiment were used to study the mechanism of PFEO through GABAergic pathway to regulate insomnia. The main volatile constituents of PFEO were analyzed by gas chromatography-mass spectrometry (GC-MS). Results The inhalation of PFEO has sedative and hypnotic effects, which reduce significantly the autonomic activity of PCPA insomnia mice, increase falling asleep rate, shorten latency of sleeping time, and prolong duration of sleeping time; the results of enzyme-linked immunosorbent assay show that PFEO increase the content of 5-HT and GABA in hypothalamus and cerebral cortex. The results showed that inhalation of PFEO increase the expression of GABAAα1 and GABAAα2 positive cells, increase the level of GABAAα1 and GABAAα2 protein and also increase the level of GABAAα1 mRNA and GABAAα2 mRNA in the hypothalamus and cerebral cortex. The highest content of PFEO is Perillaldehyde (54.37%), followed by 1,4-Cineole (7.42%), Acetaldehyde diethyl acetal (6.61%), D-Limonene (5.09%), Eucalyptol (4.94%), etc. Conclusion The inhalation of PFEO has sedative and hypnotic effects, it is speculated that the mechanism of which may be the sedative and hypnotic effects through the GABAergic pathway.

Testis has been reported to be a naturally oxygen-deprived organ. Lactate produced by glycolysis of Sertoli cells is an important source of energy in spermatogenic cells, which quickly provides adenosine triphosphate to meet the needs of rapidly proliferating spermatogenic cells for energy and substances. Wide attention has been drawn to the studies of energy metabolism and its regulatory mechanisms in normal spermatogenesis. It is essential to illuminate the regulation of glucose transport by glucose transporters in Sertoli cells, the catalysis of pyruvate to lactic acid by lactate dehydrogenase and the transport process of the single carboxylate transporter to lactic acid under the influence of different factors or diseases, which play important roles in ensuring the normal spermatogenesis and male reproductive function. This review summarizes the changes of energy metabolism in spermatogenesis and the mechanisms of endocrine factors, signaling pathways, miRNAs and protein acetylation regulating cell glycolysis, aiming to provide some important reference for the elucidation of the molecular metabolism of spermatogenesis and clinical treatment of relevant diseases.

Cooperative cognitive radio network is a new method to alleviate the spectrum scarcity problem. Proactive content caching and UAV relaying techniques are deployed in a CRN, to enable the achievable rates for primary and secondary systems. Even though these two emerging technologies are grateful to solve the problem of spectrum scarcity, there are still open issues to influence the system performance and the utilization of spectrum. In this article, we provide an overview of the cooperation technique, including their theoretical schemes and the advanced performance in radio networks. Then, this article proposes a cache-enabled UAV cooperation scheme in CRN, which enhances the CRN's transmission capability and reduces the redundant traffic load of CRN. The experimental results show that the cache-enabled UAV scheme significantly improves the achievable rates for both systems in CCRN. In addition, we present future work related to content caching, deployment of UAVs and CCRN to support radio networks.

Against the background of global climate change and anthropogenic stresses, extreme climate events (ECEs) are projected to increase in both frequency and intensity. Precipitation is one of the main climate parameters for ECE analysis. However, accurate precipitation information for extreme climate events research from dense rain gauges is still difficult to obtain in mountainous or economically disadvantaged regions. Satellite precipitation products (SPPs) with high spatial and temporal resolution offer opportunities to monitor ECE intensities and trends on large spatial scales. In this study, the accuracies of seven SPPs on multiple spatiotemporal scales in the Yangtze River Basin (YRB) during the period of 2003&ndash, 2017 are evaluated, along with their ability to capture ECE characteristics. The seven products are the Tropical Rainfall Measuring Mission, Climate Hazards Group InfraRed Precipitation with Station Data (CHIRPS) (25), CHIRPS (05), Climate Prediction Center Morphing (CMORPH), Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN)-Climate Data Record, PERSIANN-Cloud Classification System, and Global Precipitation Measurement (GPM) IMERG. Rain gauge precipitation data provided by the China Meteorological Administration are adopted as reference data. Various statistical evaluation metrics and different ECE indexes are used to evaluate and compare the performances of the selected products. The results show that CMORPH has the best agreement with the reference data on the daily and annual scales, but GPM IMERG performs relatively well on the monthly scale. With regard to ECE monitoring in the YRB, in general, GPM IMERG and CMORPH provide higher precision. As regards the spatial heterogeneity of the SPP performance in the YRB, most of the examined SPPs have poor accuracy in the mountainous areas of the upper reach. Only CMORPH and GPM IMERG exhibit superior performance, this is because they feature an improved inversion precipitation algorithm for mountainous areas. Furthermore, most SPPs have poor ability to capture extreme precipitation in the estuaries of the lower reach and to monitor drought in the mountainous areas of the upper reach. This study can provide a reference for SPP selection for ECE analysis.

Additional file 1: Table S1. Sequences for oligonucleotides.

In this study, a biosensing system based on nicking-enhanced rolling circle amplification (N-RCA) was proposed for the highly sensitive detection of cancer-related let-7a microRNA (miRNA). The sensing system consists of a padlock probe (PP), which contains a target recognition sequence and two binding sites for nicking endonuclease (NEase), and molecular beacon (MB) as reporting molecule. Upon hybridization with let-7a, the PP can be circularized by ligase. Then, the miRNA acted as polymerization primer to initiate rolling circle amplification (RCA). With the assistance of NEase, RCA products can be nicked on the cyclized PP and are displaced during the subsequent duplication process, generating numerous nicked fragments (NFs). These NFs not only induce another RCA reaction but also open the molecular beacons (MBs) via hybridization, leading to significantly amplified fluorescence signal. Under the optimized conditions, this method exhibits high sensitivity toward target miRNA let-7a with a detection limit of as low as 10 pM, a dynamic range of three orders of magnitude is achieved, and its family member is easily distinguished even with only one mismatched base. Meanwhile, it displays good recovery and satisfactory reproducibility in fetal bovine serum (FBS). Therefore, these merits endow the newly proposed N-RCA strategy with powerful implications for miRNA detection. Graphical abstract A biosensing system based on nicking-enhanced rolling circle amplification (N-RCA) for the highly sensitive detection of cancer-related let-7a microRNA.

Since toxic gas leakage may cause ecological environmental problems and even life-threatening damage, effective monitoring of toxic gas is of great importance and subject to increasing demand. However, complicated environmental factors, as well as various coexisting interferences can easily affect the sensitivity and selectivity of gas sensors, hindering their performance. Recent reports have successfully demonstrated the development of hierarchical nanostructures with desirable self-cleaning properties, yet gas sensors that can resist contamination have rarely been realized. Here, we developed a reentrant thorny ZnO/graphene hybrid nanowall structure that simultaneously repels liquid contamination and possesses NH

Our previous study showed that the srfABC operon, which was originally identified in Salmonella enterica as an SsrB-regulated operon clustered with the flagellar class 2 operon, exhibited significant cytotoxicity against insect midgut CF-203 cells and injectable insecticidal activity against Helicoverpa armigera larvae. The srfABC operon was widely distributed among bacteria, which raises the question of their biological roles in different species. In this study, we investigated the cytotoxic effect of SrfABC toxin on mammalian cell lines. When simultaneously expressed in the Escherichia coli cytoplasm, SrfABC exhibited cytotoxicity against all tested mammalian cancer cell lines (B16, 4T-1, Hep-3B, and HeLa) in a dose-dependent manner. Intracellular expression of SrfA–FLAG, SrfB–FLAG, or SrfC–FLAG also resulted in inhibition of proliferation and apoptosis on HeLa cells. When incubated with HeLa cells separately, SrfA, SrfB, and SrfC proteins alone could enter HeLa cells, then induce apoptosis and cytotoxicity. SrfC protein shifts its localization from cytoplasm to nucleus with the aid of SrfA and/or SrfB protein. Although SrfA, SrfB, and SrfC proteins alone exhibited a cytotoxic effect against HeLa cells, all three components were essential for the full cytotoxicity. Native PAGE and co-immunoprecipitation assay demonstrated that SrfA, SrfB, and SrfC proteins could interact with each other and form a heteromeric complex.

Background Castor zinc finger 1 (CASZ1) plays critical roles in various biological processes and pathologic conditions, including cancer. However, the prognostic importance and biologic functions of CASZ1 in hepatocellular carcinoma (HCC) are still unclear. Methods qRT-PCR, western blot and immunohistochemistry analyses were used to determine CASZ1 expression in HCC samples and cell lines. The clinical significance of CASZ1 was assessed in two independent study cohorts containing 232 patients with HCC. A series of in vitro and in vivo experiments were performed to explore the role and molecular mechanism of CASZ1 in HCC progression. Results Here we report that CASZ1 expression was downregulated in HCC tissues and cell lines. Low CASZ1 expression was closely correlated with aggressive clinicopathological features, poor clinical outcomes and early recurrence of HCC patients. Moreover, overexpression of CASZ1 in HCCLM3 cells significantly inhibited cell proliferation, migration, invasion in vitro and tumor growth and metastasis in vivo, whereas silencing CASZ1 significantly enhanced the above abilities of PLC/PRF/5 cells. Further mechanism study indicated that these phenotypic changes were mediated by MAPK/ERK signaling pathway and involved altered expression of MMP2, MMP9 and cyclinD1. Finally, we proved that CASZ1 exerted its tumor-suppressive effect by directly interacting with RAF1 and reducing the protein stability of RAF1. Conclusions Our study for the first time demonstrated that CASZ1 is a tumor suppressor in HCC, which may serve as a novel prognostic predictor and therapeutic target for HCC patients. Electronic supplementary material The online version of this article (10.1186/s13046-018-0720-8) contains supplementary material, which is available to authorized users.

The aim of the present study was to investigate transient receptor potential cation channel subfamily M member 2 (TRPM2), a promising therapeutic target and biomarker for pancreatic ductal adenocarcinoma (PDAC) prognosis, in addition to determining its effects regarding tumor progression and invasion. PDAC is a fatal disease with a poor prognosis, and its associated pathogenic molecular mechanisms remain to be determined. In the present study, combined analysis using genomic and transcriptomic data from two PDAC studies was performed to discover a survival‑associated biomarker of PDAC. Survival analysis for genes mutated in ≥10 patients was performed using a Kaplan‑Meier curve and tested for significance using a log‑rank test. Furthermore, gene‑expression correlation analysis was performed to determine the genes with the strongest correlations to TRPM2. In addition, a Cell Counting Kit‑8 assay, a scratch wound‑healing assay and a Transwell assay were performed in the present study to investigate the proliferative, invasive and metastatic ability of PANC‑1 cells in TRPM2‑overexpressing and downregulated groups. The mutated TRPM2 gene had a strong negative correlation with patient survival probability compared with the normal control group (P=1.06x10‑4). Expression of TRPM2 was strongly correlated with expression of probable phospholipid‑transporting ATPase IM, γ‑parvin, tudor domain containing 9, Toll‑like receptor 7 and Scm‑like with four MBT domains protein 2 according to the criterion of a correlation coefficient >0.5. Furthermore, the results of the present study demonstrated that the TRPM2 overexpression in a PDAC cell line (PANC‑1) promoted cell proliferation, invasion and metastatic ability. TRPM2 represents a potential therapeutic target and prognostic marker for patients with PDAC. TRPM2 regulates cell proliferation, invasion and migration; however, the underlying mechanism requires further investigation in future studies.

Due to the rapidly growing volume of publications, it is an urgent task to evaluate the potential impact of emerging works and identify valuable publications for the benefit of researchers with limited time. The impact of authors is significant in terms of personal promotion and fund raising. However, the criterion used to evaluate the impact of authors is largely based on credits they have received, not potential credits. We take the citation count, the most direct and widely used metric for publication popularity, as the potential impact and evaluate its predictability. To this end, we propose a neural network-based point process model for predicting the citation count of individual publications. Our approach integrates signals from paper-specific features and their citation traces, which reflect the trend of either losing or gaining popularity. The model is learned in an adversarial way, which mitigates the bias-exposure efficiently. We verify our model on the largest publicly available academic publication repository, and our model outperforms alternatives with a notable margin.

Plesiomonas shigelloides is an important fish pathogen that causes significant losses in aquaculture. Phage therapy is a new approach to overcome the problem of multidrug-resistant bacteria. Herein, a virulent phage of P. shigelloides was isolated from the intestines of grass carp. This phage belongs to the Siphoviridae family and was designated PSP01. The optimal multiplicity of infection of PSP01 was 1 with a latent period of 30 min and a lytic period of 140 min. Good activity was observed over a wide range of temperatures (-20 °C–50 °C), pH values (3–12), and NaCl concentrations (0.1–3.5%). The phage PSP01 lysis cassette is composed of 3 genes, HolPSP, LysPSP-1 and LysPSP-2. Expression of HolPSP or LysPSP-2 in Escherichia coli resulted in bacterial lysis, and a synergistic effect was observed when the HolPSP and LysPSP-1 proteins were co-expressed. In-frame deletion uncovered an important role of the transmembrane domain (TMD) in HolPSP and the signal peptide (SP) in LysPSP-2 for bacterial lysis function. The protective effects of phage PSP01 were investigated by intraperitoneal injection into grass carp infected with P. shigelloides, showing a 33.3% increase in the survival rate of the infected grass carp. Pathological analysis of the spleens from the infected grass carp revealed alleviation of the pathological symptoms. In conclusion, isolation and bacterial lysis investigations of phage PSP01 provide a new tool for the control of fish pathogens and possesses potential for aquaculture applications.

The shortage of fossil fuels and extensive environmental pollution force the development of renewable energy. To address these problems, converting solar energy to valuable fuels and chemicals by photosynthesis is thought to be a promising and prospective approach. However, the low solar energy conversion efficiency of natural photosynthesis and the poor selectivity of current artificial photosynthesis technologies significantly limit the development of solar-to-chemicals conversion. Recently, solar-driven biological inorganic hybrid systems, which integrate biological catalysts with the inorganic light-harvesting components, are proposed to overcome the limitations of artificial and natural photosynthesis. This review presents recent progress and accomplishment of the hybrid systems for the production of organic fuels and chemicals from carbon dioxide. Firstly, we introduce the working principles of three typical hybrid systems, including photovoltaic-driven biological inorganic system, microbial photoelectrochemical system, and photosensitized biological inorganic system. Then, to deeply understand the interaction between microorganisms and inorganic materials, we discuss the charge transfer between microorganisms and inorganic materials. Moreover, to improve the interaction between microorganisms and inorganic materials, the surficial morphological and chemical modification of the inorganic materials are proposed to promote the adherence of microorganisms and the charge transfer between microorganisms and inorganic materials. Finally, we discuss the current challenges for the development of the hybrid systems.