1,084 research outputs found
Deoxycholic Acid Could Induce Apoptosis and Trigger Gastric Carcinogenesis on Gastric Epithelial Cells by Quantitative Proteomic Analysis
Background. Pathologic duodenogastric reflux can induce or aggravate gastritis because of the presence of bile acids. Bile reflux has been generally considered to be associated with intestinal metaplasia and gastric cancer. However, the pathogenic mechanisms of the effects of bile acids on gastric mucosa are still unknown. Methods. To explore the mechanisms by which bile acids induce gastric mucosal lesions, we examined cell apoptosis in the gastric epithelial cell line GES-1 and investigated the changes in protein profiles of GES-1 cells in response to a bile acid deoxycholic acid using a proteomics approach. Changes in the profiles of the differently expressed proteins were analyzed using the DAVID and STRING programs. Results. We found apoptosis was significantly induced in GES-1 cells by deoxycholic acid. Using liquid chromatographic/tandem mass spectrometric (LC-MS/MS) methods, 134 upregulated proteins and 214 downregulated proteins were identified in the bile acid treated GES-1 cells. Bioinformatics analysis revealed the interactions and signaling networks of these differentially expressed proteins. Conclusion. These findings may improve the understanding of the molecular mechanisms underlying the pathogenicity of bile acids on gastric mucosa.Key laboratory for Helicobacter pylori infection and Upper Gastrointestinal Diseases, Beijing Key Laboratory [BZ0371]; Chinese National Natural Science Foundation of China [81270475]SCI(E)[email protected]
Maternal exercise represses Nox4 via SIRT1 to prevent vascular oxidative stress and endothelial dysfunction in SHR offspring
Maternal exercise during pregnancy has emerged as a potentially promising approach to protect offspring from cardiovascular disease, including hypertension. Although endothelial dysfunction is involved in the pathophysiology of hypertension, limited studies have characterized how maternal exercise influences endothelial function of hypertensive offspring. In this study, pregnant spontaneously hypertensive rats and Wistar-Kyoto rats were assigned either to a sedentary lifestyle or to swimming training daily, and fetal histone deacetylase-mediated epigenetic modification and offspring vascular function of mesenteric arteries were analyzed. Maternal exercise ameliorated the impairment of acetylcholine-induced vasodilation without affecting sodium nitroprusside-induced vasodilation in mesenteric arteries from the hypertensive offspring. In accordance, maternal exercise reduced NADPH oxidase-4 (Nox4) protein to prevent the loss of nitric oxide generation and increased reactive oxygen species production in mesenteric arteries of hypertensive offspring. We further found that maternal exercise during pregnancy upregulated vascular SIRT1 (sirtuin 1) expression, leading to a low level of H3K9ac (histone H3 lysine 9 acetylation), resulting in the transcriptional downregulation of Nox4 in mesenteric arteries of hypertensive fetuses. These findings show that maternal exercise alleviates oxidative stress and the impairment of endothelium-dependent vasodilatation via SIRT1-regulated deacetylation of Nox4, which might contribute to improved vascular function in hypertensive offspring
Text-Augmented Multimodal LLMs for Chemical Reaction Condition Recommendation
High-throughput reaction condition (RC) screening is fundamental to chemical
synthesis. However, current RC screening suffers from laborious and costly
trial-and-error workflows. Traditional computer-aided synthesis planning (CASP)
tools fail to find suitable RCs due to data sparsity and inadequate reaction
representations. Nowadays, large language models (LLMs) are capable of tackling
chemistry-related problems, such as molecule design, and chemical logic Q\&A
tasks. However, LLMs have not yet achieved accurate predictions of chemical
reaction conditions. Here, we present MM-RCR, a text-augmented multimodal LLM
that learns a unified reaction representation from SMILES, reaction graphs, and
textual corpus for chemical reaction recommendation (RCR). To train MM-RCR, we
construct 1.2 million pair-wised Q\&A instruction datasets. Our experimental
results demonstrate that MM-RCR achieves state-of-the-art performance on two
open benchmark datasets and exhibits strong generalization capabilities on
out-of-domain (OOD) and High-Throughput Experimentation (HTE) datasets. MM-RCR
has the potential to accelerate high-throughput condition screening in chemical
synthesis
Probing Product Description Generation via Posterior Distillation
In product description generation (PDG), the user-cared aspect is critical
for the recommendation system, which can not only improve user's experiences
but also obtain more clicks. High-quality customer reviews can be considered as
an ideal source to mine user-cared aspects. However, in reality, a large number
of new products (known as long-tailed commodities) cannot gather sufficient
amount of customer reviews, which brings a big challenge in the product
description generation task. Existing works tend to generate the product
description solely based on item information, i.e., product attributes or title
words, which leads to tedious contents and cannot attract customers
effectively. To tackle this problem, we propose an adaptive posterior network
based on Transformer architecture that can utilize user-cared information from
customer reviews. Specifically, we first extend the self-attentive Transformer
encoder to encode product titles and attributes. Then, we apply an adaptive
posterior distillation module to utilize useful review information, which
integrates user-cared aspects to the generation process. Finally, we apply a
Transformer-based decoding phase with copy mechanism to automatically generate
the product description. Besides, we also collect a large-scare Chinese product
description dataset to support our work and further research in this field.
Experimental results show that our model is superior to traditional generative
models in both automatic indicators and human evaluation
HMGB1/GPC3 Dual Targeting Vaccine Induces Dendritic Cells-Mediated CD8+T Cell Immune Response and Elicits Potential Therapeutic Effect in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a fatal malignant tumor, but effective clinical interventions are limited. PLGA/PEI-mediated DNA vaccine encoding the dual targets of high-mobility group box 1 (HMGB1) or GPC3 was developed for HCC treatment. Compared with PLGA/PEI-GPC3 immunization, PLGA/PEI-HMGB1/GPC3 co-immunization significantly inhibited the subcutaneous tumor growth, while increasing the infiltration of CD
A novel pathogenic avipoxvirus infecting oriental turtle dove (Streptopelia orientalis) in China shows a high genomic and evolutionary proximity with the pigeon avipoxviruses isolated globally
Avipoxviruses are considered as significant viral pathogen infecting a wide range of domestic and wild bird species globally, yet the majority of avipoxviruses that infect the wild bird species remain uncharacterized and their genetic diversities remain unclear. In this study, we present a novel pathogenic avipoxvirus isolated from the cutaneous pox lesions of a wild oriental turtle dove (Streptopelia orientalis), tentatively named as turtle dovepox virus (TDPV). The avipoxvirus was isolated by using the chorioallantoic membranes of specific pathogen-free chicken embryos which showed characteristic focal pock lesions, followed by cytopathic effects in host cells infected with oriental turtle dovepox virus. An effort in sequencing the whole genome of the poxvirus using next-generation sequencing was given, and the first whole genome sequence of TDPV was obtained. The TDPV genome was 281,386 bp in length and contained 380 predicted open reading frames (ORFs). While 336 of the predicted ORFs showed homology to other characterized avipoxviruses, the other 44 ORFs were unique. Subsequent phylogenetic analyses showed that the novel TDPV shared the closest genetic evolutionary linkage with the avipoxviruses isolated from pigeon in South Africa and India, of which the TDPV genome had the highest sequence similarity (92.5%) with South African pigeonpox virus (FeP2). In conclusion, the sequenced TDPV is significantly different from any other avipoxviruses isolated from avian or other natural host species considering genomic architecture and observed sequence similarity index. Thus, it likely should be considered a separate species. IMPORTANCE Over the past few decades, avipoxviruses have been found in a number of wild bird species including the oriental turtle dove. However, there is no whole genome sequence information on avipoxviruses isolated from oriental turtle dove, leaving us unclear about the evolutionary linkage of avipoxviruses in oriental turtle dove and other wild bird species. Thus, we believe that our study makes a significant contribution because it is the first report of the whole genome sequence of TDPV isolated from a wild oriental turtle dove, which enriches the genomic information of the genus Avipoxvirus, furthermore, contributes to tracking the genetic evolution of avipoxviruses-infected oriental turtle dove species
Topographic evolution of tidal flats based on remote sensing: an example in Jiangsu coast, Southern Yellow Sea
The topographic evolution of tidal flats is critical for local ecological conservation, coastal zone management, and physical oceanographic studies. However, obtaining this knowledge is often challenging due to the lack of frequently updated topographic data over large areas. With the explosion of remotely sensed data, the waterline method has become the most operational method for tidal flat topography acquisition. In this study, digital elevation models (DEMs) of the tidal flats around Tongzhou Bay on the Jiangsu coast were constructed using the waterline method for three periods (2013, 2015, and 2017) before and after the construction of phase I of the reclamation project. Furthermore, the topographic evolution characteristics were analyzed from four aspects: contours, area changes, erosion–deposition distribution, and typical cross-sections. The results showed that: 1) During the 5 years from 2013 to 2017, the overall tidal flat area (500 km2) of Tongzhou Bay on the Jiangsu coast had been in a state of deposition, with a total siltation thickness of 0.19 m. 2) The reclamation activities affected the topography of the tidal flats quickly, but the recovery was also rapid. During the implementation of the project (in 2015), the area of the tidal flats above the −2-m contour was rapidly reduced by 20 km2 but rapidly recovered to the pre-project level after the completion of the project (in 2017). 3) The reclamation project directly affected the distribution of erosion and siltation. Outside the seawall on the east side of the Yaosha sand ridge, the 0-m contour expanded rapidly to the outer sea, reaching more than 250 m/year. 4) The sandbars in Tongzhou Bay on the Jiangsu coast generally had a southward-moving trend. Over the past 40 years, the Yaosha sand ridge had shifted southward by 2,500 m and the Lengjiasha sand ridge by more than 5,000 m. This study provides a remote sensing solution for the topographic evolution of large tidal flats under the influence of human reclamation activities
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