2,768 research outputs found

    Effects of Sodium Sulfate Attack on Concrete Incorporated with Drying-Wetting Cycles

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    It has been widely observed that sulfate attack can damage the durability of concrete. This research investigated the mass loss and damage degree of concrete under sodium sulfate attack incorporated with drying-wetting cycles. The impact factors, including water-binder ratio, solution concentration of sodium sulfate, fly ash content, curing time, and drying-wetting cycle system, were observed to influence the sodium sulfate attack by the mass loss rate and damage degree at regular time intervals. Also, the hydrates of sulfate-attacked samples were analyzed using X-ray diffraction. Results indicated that a high water-binder and high-concentration sodium sulfate solution could accelerate the transportation of sulfate ion inside the concrete and the deterioration degree of concrete. Appropriate fly ash and longer curing time can effectively improve the internal pore structure of concrete to reduce the sulfate corrosion damage. The sulfate ion erosion and deterioration degree of the concrete are synchronously intensified along with the increase of the baking-immersing time ratio. The trend of the predicted life for concrete is basically consistent with the damage evolution result, indicating the feasibility of the Weibull distribution model to predict the service life of concrete under sodium sulfate attack incorporated with drying-wetting cycles

    GOPlan: Goal-conditioned Offline Reinforcement Learning by Planning with Learned Models

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    Offline goal-conditioned RL (GCRL) offers a feasible paradigm to learn general-purpose policies from diverse and multi-task offline datasets. Despite notable recent progress, the predominant offline GCRL methods have been restricted to model-free approaches, constraining their capacity to tackle limited data budgets and unseen goal generalization. In this work, we propose a novel two-stage model-based framework, Goal-conditioned Offline Planning (GOPlan), including (1) pretraining a prior policy capable of capturing multi-modal action distribution within the multi-goal dataset; (2) employing the reanalysis method with planning to generate imagined trajectories for funetuning policies. Specifically, the prior policy is based on an advantage-weighted Conditioned Generative Adversarial Networks that exhibits distinct mode separation to overcome the pitfalls of out-of-distribution (OOD) actions. For further policy optimization, the reanalysis method generates high-quality imaginary data by planning with learned models for both intra-trajectory and inter-trajectory goals. Through experimental evaluations, we demonstrate that GOPlan achieves state-of-the-art performance on various offline multi-goal manipulation tasks. Moreover, our results highlight the superior ability of GOPlan to handle small data budgets and generalize to OOD goals.Comment: Spotlight Presentation at Goal-conditioned Reinforcement Learning Workshop at NeurIPS, 202

    Elucidation of mechanisms of action of Wei-Sheng-Fang-Yi-Bao-Dan in the treatment of COVID-19 and depression using network pharmacology and molecular docking

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    Purpose: To investigate the mechanisms of action of Wei-Sheng-Fang-Yi-Bao-Dan (WSFYBD) in the treatment of COVID-19 and depression using network pharmacology and molecular docking. Methods: First, the bioactive components and target genes of WSFYBD were retrieved from TCMSP database. The relevant gene targets of depression and COVID-19 were obtained from databases. The core WSFYBD genes for treatment were separately obtained by determining gene intersection. Cytoscape 3.8.0 software was used to draw the visual interactive networks. STRING database was employed to construct protein-protein interaction networks, while Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were used to determine the function and pathway of target genes via a Bioconductor/R. Finally, AutoDockTools software was employed for molecular docking. Results: A total of 105 potential bio-active components and 35 target genes of WSFYBD for COVID-19 therapy were identified. Also, 1905 GO entries (p < 0.05) and 158 related signal pathways (p < 0.05) for COVID-19 were obtained. Similarly, 114 potential bio-active components of WSFYBD and 127 potential therapeutic targets of depression were identified. Moreover, 1948 GO entries (p < 0.05) and 177 related signal pathways for depression were retrieved (p < 0.05). Docking results showed the main bio-active components were closely bound to the core targets. Conclusion: The mechanisms for treating COVID-19 show that WSFYBD directly acts on SARS-CoV-2 virus to prevent it from entering the host cell, or inhibits virus replication. Secondly, WSFYBD ameliorates depression by acting on key targets that control over-activated cytokines. Therefore, WSFYBD has potentials for the management of COVID-19 and depression

    Scoulerine promotes cytotoxicity and attenuates stemness in ovarian cancer by targeting PI3K/AKT/mTOR axis

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    In women, ovarian cancer is a common gynecological cancer associated with poor prognosis, reoccurrence and chemoresistance. Scoulerine, a benzylisoquinoline alkaloid, has been reported effective against several carcinomas. Thus, we investigated the impact of scoulerine on ovarian cancer cells (OVCAR3). Cell viability was assessed by MTT assay, migration was determined by Boyden Chamber assay, while the invasion was monitored by Boyden Chamber assay using the matrigel. The stemness properties of OVCAR3 cells were observed by tumorsphere assay. Epithelial to mesenchymal transition (EMT) and stemness-related protein markers were monitored by real-time PCR analysis and immunoblotting. Scoulerine inhibits the viability of OVCAR3 cells with the IC50 observed at 10 µmol L–1 after 48 h treatment. Scoulerine inhibited the colony-forming ability, migration and invasiveness of OVCAR3 cells in a dose-dependent fashion. Scoulerine treatment also drastically reduced the spheroid-forming ability of OVCAR3 cells. The mesenchymal and stemness-related markers like N-cadherin, vimentin, CD-44, Oct-4, Sox-2 and Aldh1A1 were downregulated, whereas the epithelial markers like E-cadherin and CD-24 were upregulated in scoulerine-treated cells. The upstream PI3K/Akt/mTOR-axis was downregulated in scoulerine-treated cells. We concluded that scoulerine successfully perturbs the cancerous properties of OVCAR3 cells by targeting the PI3K/Akt/mTOR axis. In vivo studies revealed a substantial decrease in tumor mass and volume after scoulerine treatment. Furthermore, scoulerine treatment was found to decrease oxidative stress factors in ovarian cancer mice model. Scoulerine is a potential anticancer agent against ovarian cancer and can be considered as a lead molecule for this malignancy, provided further investigations are performed

    Detection of gamma-ray emission from the Coma cluster with Fermi Large Area Telescope and tentative evidence for an extended spatial structure

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    Many galaxy clusters have giant halos of non-thermal radio emission, indicating the presence of relativistic electrons in the clusters. Relativistic protons may also be accelerated by merger and/or accretion shocks in galaxy clusters. These cosmic-ray (CR) electrons and/or protons are expected to produce gamma-rays through inverse-Compton scatterings or inelastic pppp collisions respectively. Despite of intense efforts in searching for high-energy gamma-ray emission from galaxy clusters, conclusive evidence is still missing so far. Here we report the discovery of 200\ge 200 MeV gamma-ray emission from the Coma cluster direction with an unbinned likelihood analysis of the 9 years of {\it Fermi}-LAT Pass 8 data. The gamma-ray emission shows a spatial morphology roughly coincident with the giant radio halo, with an apparent excess at the southwest of the cluster. Using the test statistic analysis, we further find tentative evidence that the gamma-ray emission at the Coma center is spatially extended. The extended component has an integral energy flux of 2×1012 erg cm2 s1\sim 2\times 10^{-12}{\rm \ erg\ cm^{-2}\ s^{-1}} in the energy range of 0.2 - 300 GeV and the spectrum is soft with a photon index of 2.7\simeq-2.7. Interpreting the gamma-ray emission as arising from CR proton interaction, we find that the volume-averaged value of the CR to thermal pressure ratio in the Coma cluster is about 2%\sim 2\%. Our results show that galaxy clusters are likely a new type of GeV gamma-ray sources, and they are probably also giant reservoirs of CR protons.Comment: 10 pages, 10 figures, Accepted by Physical Review D, more spatial models for the gamma-ray emission are used, systematic checks on the results are adde

    Neoadjuvant Chemotherapy with FOLFOX4 Regimen to Treat Advanced Gastric Cancer Improves Survival without Increasing Adverse Events: A Retrospective Cohort Study from a Chinese Center

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    Background/Aim. To evaluate the clinical efficacy of FOLFOX4 (5-fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC). Patients and Methods. Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared. Results. The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0–49) versus 13 (3–40)) between the two groups (P>0.05). The number of lymph node metastases in the neoadjuvant group (3 (0–14)) was significantly fewer than that in the adjuvant group (6 (0–27)) (P=0.04). The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group (P=0.013). The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P=0.015). Conclusion. The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC

    Effect of Hedyotis diffusa Willd extract on gouty arthritis in rats

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    Purpose: To investigate the effect of Hedyotis diffusa Willd extract (HDWE) on gouty arthritis in rats.Method: Monosodium urate (MSU) crystal was injected into the ankle joint of rats to establish a rat model of gouty arthritis. HDWE (4.8, 9.6 and 19.2 g/kg) was administered to the rats treated with MSU crystals. The walking behavior of the rats was observed daily, and the gait score was calculated to evaluate the Oswestry disability index of rats. Levels of IL-1β and TNF-α in lavage fluid of articularcavities were measured using enzyme linked immunosorbent assay (ELISA) kits. The synovial tissues of joint of control, model and 19.2 g/kg HDWE group rats were obtained and NLRP3 inflammasome was analysed by Western blot.Results: The results showed that HDWE ameliorated the symptoms of gouty arthritis and gait score in rats significantly (p < 0.05). Further pharmacological experiments showed that all doses of HDWE decreased the levels of inflammatory cytokines IL-1β and TNF-α (p < 0.05), and inhibited NLRP3, caspase-1, ASC, IL-1β and IL-18 protein expressions of the lavage fluid of articular cavities in MSU crystal-treated rats (p < 0.01).Conclusion: The results indicate that HDWE exhibits a significant effect in ameliorating gouty arthritis via inhibition NLRP3  inflammasome, and thus is a potential new drug choice for the treatment of gouty arthritis. Keywords: Hedyotis diffusa, Caspase, Gouty arthritis, Inflammatory cytokines, NLRP3 inflammaso

    miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.

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    MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis
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