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Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

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The real-time detection and counting of rice ears in fields is one of the most important methods for estimating rice yield. The traditional manual counting method has many disadvantages: it is time-consuming, inefficient and subjective. Therefore, the use of computer vision technology can improve the accuracy and efficiency of rice ear counting in the field. The contributions of this article are as follows. (1) This paper establishes a dataset containing 3300 rice ear samples, which represent various complex situations, including variable light and complex backgrounds, overlapping rice and overlapping leaves. The collected images were manually labeled, and a data enhancement method was used to increase the sample size. (2) This paper proposes a method that combines the LC-FCN (localization-based counting fully convolutional neural network) model based on transfer learning with the watershed algorithm for the recognition of dense rice images. The results show that the model is superior to traditional machine learning methods and the single-shot multibox detector (SSD) algorithm for target detection. Moreover, it is currently considered an advanced and innovative rice ear counting model. The mean absolute error (MAE) of the model on the 300-size test set is 2.99. The model can be used to calculate the number of rice ears in the field. In addition, it can provide reliable basic data for rice yield estimation and a rice dataset for research.

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Posture changes in pigs during growth are often precursors of disease. Monitoring pigs' behavioral activities can allow us to detect pathological changes in pigs earlier and identify the factors threatening the health of pigs in advance. Pigs tend to be farmed on a large scale, and manual observation by keepers is time consuming and laborious. Therefore, the use of computers to monitor the growth processes of pigs in real time, and to recognize the duration and frequency of pigs' postural changes over time, can prevent outbreaks of porcine diseases. The contributions of this article are as follows: (1) The first human-annotated pig-posture-identification dataset in the world was established, including 800 pictures of each of the four pig postures: standing, lying on the stomach, lying on the side, and exploring. (2) When using a deep separable convolutional network to classify pig postures, the accuracy was 92.45%. The results show that the method proposed in this paper achieves adequate pig-posture recognition in a piggery environment and may be suitable for livestock farm applications.

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BACKGROUND: Multidrug resistance (MDR) frequently contributes to the failure of chemotherapeutic treatments in patients diagnosed with hepatocellular carcinoma (HCC). Revealing the molecular mechanism of MDR is indispensable for the development of effective chemotherapeutic drugs. PURPOSE: Due to the low-toxicity modulators to inhibit MDR, we considered that Kanglaite (KLT) is a potential agent for reversing MDR in HCC. MATERIALS AND METHODS: BEL-7402/5-fluorouracil (5-FU) and HepG2/adriamycin (ADM) were analyzed for cell viability, colony formation assay, cell scratch assay, and cell cycle analysis and apoptosis assay by flow cytometry. The expression of PARP, caspase-3, Bax, Bcl-2, CDC25C, Cyclin B1 and phosphorylation of PTEN, PI3K, and AKT in HepG2/ADM cells were detected by western blotting. RESULTS: The proliferation of drug-resistant cell lines BEL-7402/5-FU and HepG2/ADM pretreated with KLT was significantly inhibited when compared with drug alone. KLT could increase the accumulation of ADM in HepG2/ADM cells. In this study, we found that KLT treatment notably reduced cell viability, induced apoptosis and cell cycle arrest in human HepG2/ADM and BEL-7402/5-FU cells, and effectively reversed the MDR by p-glycoprotein (P-gp) inhibition. Moreover, KLT decreased the phosphorylation of AKT and PI3K in KLT-treated HepG2/ADM cells. These data together implied that KLT might reverse drug resistance in HCC by blocking the PI3K/AKT signaling. CONCLUSION: We demonstrated that KLT reversed MDR of human HCC by inducing apoptosis and cell cycle arrest via the PI3K/AKT signaling pathway.

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BACKGROUND: As microRNA-34a (miR-34a) has been suggested to be associated with breast cancer (BC), this study was proposed to explore the underlying mechanism of miR-34a in suppressing BC progression. METHODS: A total of 123 pairs of tumor tissues and matched nontumor tissues were obtained from patients. Reverse transcription polymerase chain reaction and in situ hybridization were used to detect the differences in miR-34a expression in tissues and cells. Whether Wnt1 is a direct downstream target of miR-34a was confirmed by both bioinformatics target gene prediction and dual-luciferase report assay. Wnt1 and other gene expressions that are related to Wnt/ß-catenin signaling pathway were assessed by reverse transcription polymerase chain reaction and western blot when MCF-7A cells were transfected with miR-34a mimic or miR-34a inhibitor. The proliferation, invasion and migration status of MCF-7 cells after transfection were assessed by MTT assay, wound healing assay and transwell assays, respectively. Breast tumor xenograft models on mice were also constructed to determine the effect of miR-34a on breast tumor growth in vivo. RESULTS: MiR-34a expression was remarkably down-regulated in BC tissues and cell lines compared with normal tissues and cell lines. Wnt1 was a direct downstream target of miR-34a and low expression of miR-34a contributed to the Wnt/ß-catenin signaling pathway activation in MCF-7A cells. MiR-34a inhibited the proliferation, invasion and migration of BC in vitro and breast tumor growth in vivo through deactivating the Wnt/ß-catenin signaling pathway. CONCLUSION: MiR-34a may suppress the proliferation and progression of BC via mediating the Wnt/ß-catenin signaling pathway.

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Triptolide is a diterpene triepoxide compound extracted from the medicinal plant, Tripterygium wilfordii Hook F. The aim of the present study was to determine whether triptolide inhibits the proliferation of breast cancer cells and to further investigate the associated molecular mechanisms. The effects of triptolide on the cell viability of three breast cancer cell lines, specifically, highly metastatic MDA-MB-231, human epidermal growth factor receptor 2-positive BT-474 and estrogen receptor-positive MCF7 cells, were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptosis assays. Western blot analysis was performed to investigate the expression levels of ß-catenin in the control and triptolide-treated cells. The results demonstrated that triptolide treatment caused cell death in the three types of malignant cell lines. Treatment with 25 nM triptolide for 48 h exhibited marked inhibitory effects on the cell viability of the three types of cells, with greater effects observed in BT-474 cells compared with the other two cell types. When compared with the cells not treated with triptolide, 50 nM triptolide treatment resulted in apoptosis of MDA-MB-231, BT-474 and MCF7 cells with apoptotic rates of ~80%. Western blot analysis indicated that triptolide treatment of MDA-MB-231, BT-474 and MCF7 cells decreased the expression levels of ß-catenin to 5-10% of the levels observed in the cells treated with dimethyl sulfoxide only. Therefore, the results of the present study indicate that triptolide induces the apoptosis of breast cancer cells via a mechanism associated with the Wnt/ß-catenin signaling pathway.

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Matrine is an alkaloid isolated from Sophora flavescens. The present study aimed to determine whether matrine effectively inhibits the proliferation of breast cancer cells, and the underlying mechanism(s) of its antitumor function. The effects of matrine on the cell viability of ER-positive MCF7 cells, HER2-positive BT-474 cells and highly metastatic MDA-MB-231 cells were measured using MTT and apoptosis assays. Western blot analysis was performed to investigate the expression levels of the inhibitor of κB (IκB) kinase ß (IKKß) in cells treated with or without matrine. It was observed that the matrine treatment resulted in the death of the three types of cancer cells, but significantly less toxicity was observed in the control cancer cells. The experimental results also suggested that the antitumor effects of matrine on breast cancer cells may be associated with the downregulation of IKKß expression by matrine, as indicated by the western blot analysis results. The present results suggested that matrine may be used as an effective drug candidate for treating breast cancers in the future, following further research.

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The fluorescence emission of Rhodamine 6G molecules at the physically polished nanostructured copper surface with varying thickness of the native oxide layer was investigated. The quenching effect was observed when the dye molecule was directly adsorbed onto the substrate surface without the formative oxide layer. However, the fluorescence was enhanced obviously when the native oxide layer was formed at the substrate surface. The experimental observations were discussed by taking into account the formation of the native oxide layer, the non-radiative energy transfer process and the local surface plasmon resonance at rough copper surface. The study highlights the importance of the native oxide layer formed on the metal substrate in surface enhanced fluorescence.