Neferine induces apoptosis of pancreatic cancer cells through p38 MAPK/JNK activation

Purpose: To investigate the functional role of neferine on pancreatic cancer (PC) cell apoptosis. Methods: The pancreatic cell line, PANC-1 cells, was exposed with different concentration of neferine. CCK8 and flow cytometry (Cell counting kit-8) were carried out to detect cell proliferation and apoptosis. Protein expression was evaluated by western blot. Results: Neferine suppressed cell viability and caused cell cycle arrest of pancreatic cells in a dosedependent way. The effect of neferine on pancreatic cells was dependent on its ability to regulate the expression of cyclin E, cyclin D1, p21, cleaved caspase-3, cleaved PARP, Bcl-2 and Bax. In addition, neferine treatment induced the apoptosis of PANC-1 cells via promoting the activation of p38 MAPK/JNK signaling pathway. Conclusions: Neferine inhibits cell viability and proliferation, and promotes apoptosis of PC cells by activating p38 MAPK/JNK signaling pathway. These results indicated the potential therapeutic effect of neferine in the treatment of PC

EvalCrafter: Benchmarking and Evaluating Large Video Generation Models

The vision and language generative models have been overgrown in recent years. For video generation, various open-sourced models and public-available services are released for generating high-visual quality videos. However, these methods often use a few academic metrics, for example, FVD or IS, to evaluate the performance. We argue that it is hard to judge the large conditional generative models from the simple metrics since these models are often trained on very large datasets with multi-aspect abilities. Thus, we propose a new framework and pipeline to exhaustively evaluate the performance of the generated videos. To achieve this, we first conduct a new prompt list for text-to-video generation by analyzing the real-world prompt list with the help of the large language model. Then, we evaluate the state-of-the-art video generative models on our carefully designed benchmarks, in terms of visual qualities, content qualities, motion qualities, and text-caption alignment with around 18 objective metrics. To obtain the final leaderboard of the models, we also fit a series of coefficients to align the objective metrics to the users' opinions. Based on the proposed opinion alignment method, our final score shows a higher correlation than simply averaging the metrics, showing the effectiveness of the proposed evaluation method.Comment: Technical Report, Project page: https://evalcrafter.github.io

VideoCrafter1: Open Diffusion Models for High-Quality Video Generation

Video generation has increasingly gained interest in both academia and industry. Although commercial tools can generate plausible videos, there is a limited number of open-source models available for researchers and engineers. In this work, we introduce two diffusion models for high-quality video generation, namely text-to-video (T2V) and image-to-video (I2V) models. T2V models synthesize a video based on a given text input, while I2V models incorporate an additional image input. Our proposed T2V model can generate realistic and cinematic-quality videos with a resolution of $1024 \times 576$, outperforming other open-source T2V models in terms of quality. The I2V model is designed to produce videos that strictly adhere to the content of the provided reference image, preserving its content, structure, and style. This model is the first open-source I2V foundation model capable of transforming a given image into a video clip while maintaining content preservation constraints. We believe that these open-source video generation models will contribute significantly to the technological advancements within the community.Comment: Tech Report; Github: https://github.com/AILab-CVC/VideoCrafter Homepage: https://ailab-cvc.github.io/videocrafter

PAI-1 Exacerbates White Adipose Tissue Dysfunction and Metabolic Dysregulation in High Fat Diet-Induced Obesity

Background: Plasminogen activator inhibitor (PAI)-1 levels and activity are known to increase during metabolic syndrome and obesity. In addition, previous studies have implicated PAI-1 in adipose tissue (AT) expansion while also contributing to insulin resistance. As inflammation is also known to occur in AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model PAI-1 contributes to macrophage-mediated inflammation and metabolic dysfunction.Methods: Four- to five-weeks-old male C57B6/6J mice were fed a HFD (45%) for 14 weeks, while age-matched control mice were fed a standard laboratory chow diet (10% fat). Additional studies were performed in PAI-1 knockout mice and wild type mice treated with an inhibitor (PAI-039) of PAI-1. Macrophage polarization were measured by real time PCR.Results: HFD mice showed increased expression of PAI-1 in visceral white AT (WAT) that also displayed increased macrophage numbers. PAI-1 deficient mice exhibited increased numbers of anti-inflammatory macrophages in WAT and were resistant to HFD-induced obesity. Similarly, pharmacological inhibition of PAI-1 using PAI-039 significantly decreased macrophage infiltration in WAT and improved metabolic status in HFD-induced wild-type mice. Importantly, the numbers of M1 macrophages appeared to be increased by the HFD and decreased by either genetic PAI-1 depletion or PAI-039 treatment.Conclusions: Collectively, our findings provide support for PAI-1 contributing to the development of inflammation in adipose tissue and explain the mechanism of inflammation modulated by PAI-1 in the disordered metabolism in HFD-induced obesity

Structural insights into Ca2+-activated long-range allosteric channel gating of RyR1

Ryanodine receptors (RyRs) are a class of giant ion channels with molecular mass over 2.2 mega-Daltons. These channels mediate calcium signaling in a variety of cells. Since more than 80% of the RyR protein is folded into the cytoplasmic assembly and the remaining residues form the transmembrane domain, it has been hypothesized that the activation and regulation of RyR channels occur through an as yet uncharacterized long-range allosteric mechanism. Here we report the characterization of a Ca2+-activated open-state RyR1 structure by cryo-electron microscopy. The structure has an overall resolution of 4.9 angstrom and a resolution of 4.2 angstrom for the core region. In comparison with the previously determined apo/closed-state structure, we observed long-range allosteric gating of the channel upon Ca2+ activation. In-depth structural analyses elucidated a novel channel-gating mechanism and a novel ion selectivity mechanism of RyR1. Our work not only provides structural insights into the molecular mechanisms of channel gating and regulation of RyRs, but also sheds light on structural basis for channel-gating and ion selectivity mechanisms for the six-transmembrane-helix cation channel family.Strategic Priority Research Program of Chinese Academy of Sciences [XDB08030202]; National Basic Research Program (973 Program); Ministry of Science & Technology of China [2012CB917200, 2014CB910700]; National Natural Science Foundation of China [31270768]; Ministry of Education of China (111 Program China)SCI(E)PubMed中国科技核心期刊(ISTIC)[email protected]; [email protected]

Application of Tucker Decomposition in Temperature Distribution Reconstruction

Constrained by cost, measuring conditions and excessive calculation, it is difficult to reconstruct a 3D real-time temperature field. For the purpose of solving these problems, a three-dimensional temperature distribution reconstruction algorithm based on Tucker decomposition algorithm is proposed. The Tucker decomposition algorithm is used to reduce the dimension of the measured data, and the processed core tensor is used for the temperature field reconstruction of sparse data. Theoretical analysis and simulations show that the proposed method is feasible; the overall optimization is realized by selecting the appropriate core tensor dimensions; and the reconstruction error is less than 3%. Results indicate that the proposed method can yield a reliable reconstruction solution and can be applied to real-time applications

Landscape Changes and Optimization in an Ecological Red Line Area: A Case Study in the Upper Reaches of the Ganjiang River

The key to optimizing ecological management is to study the spatial configuration of the landscape and the dynamic changes and their driving mechanisms at the landscape scale. The ecological red line area in the hilly area of the upper reaches of the Ganjiang River was chosen as the research area in this study. Based on the theory of landscape ecology and the evolution of biological communities, a multiscale coupling model was adopted and combined with remote sensing (RS) and geographical information system (GIS) technologies to systematically study the evolution of key landscape ecosystems such as forests, patch characteristics, and changes in diversity. The study revealed that: (1) forests represented the largest proportion in the study area, followed by croplands and grasslands; (2) the biological community tended to progress toward climax between 1986 and 1995, but then it moved toward regressive successions between 1995 and 2005 before recovering; (3) the study area was characterized by a high proportion of dominant ecosystems, most of which were at their climax with stable ecological species groups, and which were connected by ecological corridors; and (4) during the period from 1995 to 2010, most landscapes showed a trend of fragmentation. However, during the period from 2010 to 2018, the forest patches were gradually connected. The proportion of dominant landscapes increased, and the landscape uniformity was reduced. Based on the findings, we proposed an ecosystem management strategy that includes strengthening crop management, focusing on the natural restoration of the ecosystems and the cultivation of large patches, exploring disturbances due to mining activities, and applying methods to mitigate damage to and optimize the ecosystem

www.mdpi.com/journal/ijms Detection of Promyelocytic Leukemia/Retinoic Acid Receptor α (PML/RARα) Fusion Gene with Functionalized Graphene Oxide

Abstract: An attempt was made to use functionalized graphene oxide (GO) to detect the Promyelocytic leukemia/Retinoic acid receptor α fusion gene (PML/RARα fusion gene), a marker gene of acute promyelocytic leukemia. The functionalized GO was prepared by chemical exfoliation method, followed by a polyethylene glycol grafting. It is found that the functionalized GO can selectively adsorb the fluorescein isothiocyanate (FITC)-labeled single-stranded DNA probe and quench its fluorescence. The probe can be displaced by the PML/RARα fusion gene to restore the fluorescence, which can be detected by laser confocal microscopy and flow cytometry. These can be used to detect the presence of the PML/RARα fusion gene. This detection method is verified to be fast, simple and reliable

Bioactivity-guided fractionation of an antidiarrheal Chinese herb Rhodiola kirilowii (Regel) Maxim reveals (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate as inhibitors of cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis transmembrane conductance regulator (CFTR) is the principal apical route for transepithelial fluid transport induced by enterotoxin. Inhibition of CFTR has been confirmed as a pharmaceutical approach for the treatment of secretory diarrhea. Many traditional Chinese herbal medicines, like Rhodiola kirilowii (Regel) Maxim, have long been used for the treatment of secretory diarrhea. However, the active ingredients responsible for their therapeutic effectiveness remain unknown. The purpose of this study is to identify CFTR inhibitors from Rhodiola kirilowii (Regel) Maxim via bioactivity-directed isolation strategy. We first identified fractions of Rhodiola kirilowii (Regel) Maxim that inhibited CFTR Cl- channel activity. Further bioactivity-directed fractionation led to the identification of (-)-epigallocatechin-3-gallate (EGCG) as CFTR Cl- channel inhibitor. Analysis of 5 commercially available EGCG analogs including (+)-catechins (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG) and EGCG revealed that ECG also had CFTR inhibitory activity. EGCG dose-dependently and reversibly inhibited CFTR Cl- channel activity in transfected FRT cells with an IC50 value around 100 μM. In ex vivo studies, EGCG and ECG inhibited CFTR-mediated short-circuit currents in isolated rat colonic mucosa in a dose-dependent manner. In an intestinal closed-loop model in mice, intraluminal application of EGCG (10 μg) and ECG (10 μg) significantly reduced cholera toxin-induced intestinal fluid secretion. CFTR Cl- channel is a molecular target of natural compounds EGCG and ECG. CFTR inhibition may account, at least in part, for the antidiarrheal activity of Rhodiola kirilowii (Regel) Maxim. EGCG and ECG could be new lead compounds for development of CFTR-related diseases such as secretory diarrhea