Four novel tetracyclic oxindole alkaloids, namely, speradines B (1), C(2), D (3), and E (4) were isolated from the marine-derived fungus Aspergillus oryzae.The structures of these compounds without the absolute configurations were elucidated through 1D and 2D nuclear magnetic resonance and high-resolution mass spectrometric analyses.Among these compounds, 1 and 4 showed weak cytotoxic effects on the HeLa cell line.Indole-terpenes are fungal and bacterial secondary metabolites with unique biological activities such as inhibitory activity of calcium-activated potassium channels, 1 antitumor activity, 2 tremorgenic activity, 3 potent and selective progesterone receptor agonistic activity, 4 and anti-MRSA activity. 5Cyclopiazonic acid (CPA)-type alkaloids are one important group of indole-terpenes, and they usually contain three structural units: an indole, a dimethylallyl (DMA), and two acetic acids.Only six analogous natural products have been reported to date, including α-cyclopiazonic acid, 6 iso-α-cyclopiazonic acid, 7 β-cyclopiazonic acid, 6 α-acetyl-γ-(β-indolyl)methyl-tetramic acid, 8 speradine A, 9 and 3-hydroxyl speradine A. 10 In our search for novel anticancer compounds, 11 a strain of Aspergillus oryzae showed significant cytotoxic activity.Further chemical study led to isolation and structure elucidation of four new 1662
Weakly-supervised temporal action localization (WTAL) aims to detect action instances given only video-level labels. To address the challenge, recent methods commonly employ a two-branch framework, consisting of a class-aware branch and a class-agnostic branch. In principle, the two branches are supposed to produce the same actionness activation. However, we observe that there are actually many inconsistent activation regions. These inconsistent regions usually contain some challenging segments whose semantic information (action or background) is ambiguous. In this work, we propose a novel Actionness Inconsistency-guided Contrastive Learning (AICL) method which utilizes the consistent segments to boost the representation learning of the inconsistent segments. Specifically, we first define the consistent and inconsistent segments by comparing the predictions of two branches and then construct positive and negative pairs between consistent segments and inconsistent segments for contrastive learning. In addition, to avoid the trivial case where there is no consistent sample, we introduce an action consistency constraint to control the difference between the two branches. We conduct extensive experiments on THUMOS14, ActivityNet v1.2, and ActivityNet v1.3 datasets, and the results show the effectiveness of AICL with state-of-the-art performance. Our code is available at https://github.com/lizhilin-ustc/AAAI2023-AICL.
Four new aculeatusquinones A-D (1-4) and five known compounds, (5aS,6S,7S)-3,7-dihydroxy-6-methoxy-1, 4,6,9-tetramethyl-6,7-dihydro-5aHdibenzo[b,e][1,4]dioxepine-8,11-dione (5), 3,8-dihydroxy-1,4,6,9-tetramethyldibenzo[b,e][1,4]dioxepin-11-one (6), 4-O-demethylbarbatic acid (7), atraric acid (8), and 2,5-dimethyl-1,3-benzenediol (9), were isolated from the marine-derived fungus Aspergillus aculeatus.The structures of the new compounds were elucidated by spectroscopic methods, including one-and two-dimensional NMR and high-resolution mass spectrometric analyses.Two new compounds (2 and 4) showed cytotoxic effects on the HL-60, K562, and A-549 cell lines, with IC 50 values ranging from 5.4 μM to 76.1 μM.Numerous natural products with novel structures and distinct biological activities have been discovered as the secondary metabolites of marine-derived microbes, 1 and some have been used as drugs, for example, echinocandins (antifungal drugs), ergot alkaloids (for the treatment of migraine), cyclosporine (an immunosuppressive drug), and lovastatin (a cholesterol-lowering drug). 2 To search for new anticancer compounds, more than 300 microbial strains isolated from sediment samples collected from the Min River estuary in China were screened for cytotoxicity against HL-60 cell. 3Among these strains, a fungal strain identified as Aspergillus aculeatus showed significant cytotoxic activity.The broth extract of A.aculeatus was separated by chromatography on Si gel and Sephadex LH-20 columns and then purified by
A rare hexacyclic oxindole alkaloid, speradine F (1), together with two novel tetracyclic oxindole alkaloids, speradines G (2) and H (3), were isolated from the marine-derived fungus Aspergillus oryzae. Their structures were determined by spectroscopic methods and X-ray diffraction analysis. This study is the first report on cyclopiazonic acid (CPA)-type alkaloids with a hexacyclic skeleton.
In this work, we consider the problem of cross-domain 3D action recognition in the open-set setting, which has been rarely explored before. Specifically, there is a source domain and a target domain that contain the skeleton sequences with different styles and categories, and our purpose is to cluster the target data by utilizing the labeled source data and unlabeled target data. For such a challenging task, this paper presents a novel approach dubbed CoDT to collaboratively cluster the domain-shared features and target-specific features. CoDT consists of two parallel branches. One branch aims to learn domain-shared features with supervised learning in the source domain, while the other is to learn target-specific features using contrastive learning in the target domain. To cluster the features, we propose an online clustering algorithm that enables simultaneous promotion of robust pseudo label generation and feature clustering. Furthermore, to leverage the complementarity of domain-shared features and target-specific features, we propose a novel collaborative clustering strategy to enforce pair-wise relationship consistency between the two branches. We conduct extensive experiments on multiple cross-domain 3D action recognition datasets, and the results demonstrate the effectiveness of our method.
The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin's lymphoma population, primarily consisting of patients with DLBCL.
Methods
Patients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2 mg/kg and the 3 mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells.
Results
Thirty patients were enrolled, 10 at 2 mg/kg and 20 at 3 mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3 mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7 months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance.
Conclusions
AZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing.
Trial registration
Registered at ClinicalTrials.gov: NCT01563302. First submitted 2/13/2012.
Nuclear magnetic resonance (NMR) technique benefits from high magnetic field not only due to the field-enhanced measurement sensitivity and resolution, but also because it is a powerful tool to investigate field-induced physics in modern material science. In this study, we successfully performed NMR measurements in high flat-top pulsed magnetic field (FTPMF) up to 40 T. A two-stage corrected FTPMF with fluctuation less than 10 mT and duration longer than 9 ms was established. Besides, a Giga-Hz NMR spectrometer and a sample probe suitable for pulsed-field condition were developed. Both free-induction-decay and spin-echo sequences were exploited for the measurements. The derived $^{93}$Nb NMR results show that the stability and homogeneity of the FTPMF reach an order of 10$^2$ ppm / 10 ms and 10$^2$ ppm / 10 mm$^3$ respectively, which is approaching a degree of maturity for some researches on condensed matter physics.
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