In order to improve the performance of internet public sentiment analysis, a text sentiment analysis method combining Latent Dirichlet Allocation (LDA) text representation and convolutional neural ...network (CNN) is proposed. First, the review texts are collected from the network for preprocessing. Then, using the LDA topic model to train the latent semantic space representation (topic distribution) of the short text, and the short text feature vector representation based on the topic distribution is constructed. Finally, the CNN with gated recurrent unit (GRU) is used as a classifier. According to the input feature matrix, the GRU-CNN strengthens the relationship between words and words, text and text, so as to achieve high accurate text classification. The simulation results show that this method can effectively improve the accuracy of text sentiment classification.
Electrochemiluminescence (ECL) plays a key role in analysis and sensing because of its high sensitivity and low background. Its wide applications are however limited by a lack of highly tunable ECL ...luminophores. Here we develop a scalable method to design ECL emitters of covalent organic frameworks (COFs) in aqueous medium by simultaneously restricting the donor and acceptor to the COFs' tight electron configurations and constructing high-speed charge transport networks through olefin linkages. This design allows efficient intramolecular charge transfer for strong ECL, and no exogenous poisonous co-reactants are needed. Olefin-linked donor-acceptor conjugated COFs, systematically synthesized by combining non-ECL active monomers with C
or C
symmetry, exhibit strong ECL signals, which can be boosted by increasing the chain length and conjugation of monomers. The present concept demonstrates that the highly efficient COF-based ECL luminophores can be precisely designed, providing a promising direction toward COF-based ECL phosphors.
Anhedonia is the inability to experience pleasure from rewarding or enjoyable activities and is a core symptom of depression in humans. Here, we describe a protocol for the measurement of anhedonia ...in mice, in which anhedonia is measured by a sucrose preference test (SPT) based on a two-bottle choice paradigm. A reduction in the sucrose preference ratio in experimental relative to control mice is indicative of anhedonia. To date, inconsistent and variable results have been reported following the use of the SPT by different groups, probably due to the use of different protocols and equipment. In this protocol, we describe how to set up a clearly defined apparatus for SPT and provide a detailed protocol to ensure greater consistency when carrying out SPT. This optimized protocol is highly sensitive, reliable, and adaptable for evaluation of chronic stress-related anhedonia, as well as morphine-induced dependence. The whole SPT, including adaptation, baseline measurement, and testing, takes 8 d.
The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only ...plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE
, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Objectives
We aim to evaluate the analgesic efficacy and safety of erector spinae plane block (ESPB) for postoperative analgesia in breast cancer surgeries.
Methods
PubMed, Web of ...Science, CBM, Embase, Cochrane, Wanfang, VIPP, and CNKI were searched to identify published eligible randomized controlled trials. The primary results were the postoperative 24 h morphine consumption and pain scores, while the secondary outcomes included pain scores at other times, press times of patient‐controlled intravenous analgesia (PCIA), times to request for first rescue analgesia, the incidence of request for rescue analgesia, opioid‐related complications, nerve blocks related complications and patient satisfaction.
Results
We included 20 studies meeting the inclusion criteria, which involved 1293 participants. The morphine consumption and the pain scores during 24 h postoperatively were significantly decreased in the ESPB group versus the control group (p < 0.00001). Furthermore, ESPB also reduced pain scores at other time points, press times of PCIA, and times to first rescue analgesia requirement. Meanwhile, there was a lower incidence of postoperative nausea and vomiting, and skin pruritus in the ESPB group than in the control group.
Conclusions
Compared to general anesthesia alone, ESPB combined with general anesthesia can effectively reduce the postoperative pain intensity within 48 h and opioid consumption within 24 h after breast cancer surgery, and reduce the incidence of opioid and nerve blocks related complications.
Intestinal epithelial barrier dysfunction, which involves myosin light chain kinase (MLCK) activation, contributes to the occurrence and progression of inflammation in inflammatory bowel disease ...(IBD). Wogonoside helps maintain intestinal homeostasis in mice with dextran sulfate sodium (DSS)-induced colitis, but it is unclear whether it modulates intestinal barrier function.
Here, we demonstrate that wogonoside protects against intestinal barrier dysfunction in colitis via the MLCK/pMLC2 pathway both in vivo and in vitro.
Caco-2 cell monolayers treated with the proinflammatory cytokine TNF-α showed barrier dysfunction and were assessed in the absence and presence of wogonoside for various physiological, morphological, and biochemical parameters. Colitis was induced by 3% DSS in mice, which were used as an animal model to explore the pharmacodynamics of wogonoside. We detected MLCK/pMLC2 pathway proteins via western blot analysis, assessed the cytokines IL-13 and IFN-γ via ELISA, tested bacterial translocation via fluorescence in situ hybridization (FISH) and a proper sampling of secondary lymphoid organs for bacterial culture. In addition, the docking affinity of wogonoside and MLCK was observed with DS2.5 software.
Wogonoside alleviated the disruption of transepithelial electrical resistance (TER) in TNF-α exposured Caco-2 cell; FITC-dextran hyperpermeability; loss of the tight junction (TJ) proteins occludin, ZO-1 and claudin-1 in Caco-2 cell monolayers; and bacterial translocation in colitic mice. Moreover, wogonoside reduced the levels of the proinflammatory cytokines IL-13 and IFN-γ to maintain intestinal immune homeostasis. Transmission electron microscopy (TEM) confirmed that wogonoside ameliorated the destruction of intestinal epithelial TJs. Wogonoside not only inhibited the cytoskeletal F-actin rearrangement induced by TNF-α, stabilized the cytoskeletal structure, suppressed MLCK protein expression, and reduced MLC2 phosphorylation. In addition, the results of molecular docking analysis showed that wogonoside had a high affinity for MLCK and formed hydrogen bonds with the amino acid residue LYS261 and π bonds with LYS229.
Collectively, our study indicates that wogonoside alleviates colitis by protecting against intestinal barrier dysfunction, and the potential mechanism may involve regulation of TJs via the MLCK/pMLC2 signaling pathway. Meanwhile, our study also explains the success of S. baicalensis in the treatment of ulcerative colitis (UC).
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Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal ...cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.
Chiral cholesteric molecular tweezer 7a was synthesized, and its recognition properties for Ag+, Al3+, Ca2+ etc., were investigated by UV and fluorescence spectra. The results showed that in ...ethanol/Tris (1/1, v/v, pH 7.0) buffer solution, the host molecular tweezer 7a had a specific recognition ability for Ag+, the detection limit was up to 1 × 10−6 mol/L, and other metal ions had little effect on Ag+ recognition. At the same time, the naked-eye detection of Ag+ was realized by the light red color of the complex solution. Furthermore, the mechanism of recognition of Ag+ by molecular tweezer 7a was studied by a nuclear magnetic titration test and computer molecular simulation, and a rapid detection method of Ag+ using host molecular tweezer 7a was established. Through the determination of Ag+ in milk powder, quinoa and other food samples, it was proved that this novel method had a good application prospect for the detection of Ag+ in food.
RNA-binding proteins (RBPs) regulate the expression of thousands of transcripts, and some are reported to be involved in human tumorigenesis. However, little is known about the dysregulation of RBPs ...at the genomic level in human cancers. Here, we conducted comprehensive analyses for expression, somatic copy number alteration (SCNA), and mutation profiles of 1,542 RBPs in ∼7,000 clinical specimens across 15 cancer types. We identified markedly dysregulated RBPs and found that downregulation was a predominant pattern in cancer. Combined with recurrent SCNA data, we identified 76 RBPs as potential drivers. We also discovered a set of 139 RBPs that were significantly mutated in cancers. We confirmed the oncogenic property of six RBPs in colorectal and liver cancer cell lines by using in vitro functional experiments. Our study highlights the potential roles of RBPs in carcinogenesis and lays the groundwork to better understand the functions and mechanisms of RBPs in cancer.
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•The genomic landscape of RBPs was characterized across 15 human cancer types•RBPs showed predominant downregulation in tumors in relation to normal tissues•A group of significantly cancer-related RBPs was identified•The effect of NSUN6, ZC3H13, BYSL, ELAC1, RBMS3, and ZGPAT on cell viability was shown
Wang et al. characterize transcriptional and genomic alterations in the landscape of RNA-binding proteins (RBPs) in ∼7,000 clinical samples across 15 human cancer types and experimentally validate the effects of several cancer-related RBPs on cell viability.
One-third of the world's population has been infected with
(
), a primary pathogen of the mammalian respiratory system, while about 10% of latent infections progress to active tuberculosis (TB), ...indicating that host and environmental factors may determine the outcomes such as infection clearance/persistence and treatment prognosis. The gut microbiota is essential for development of host immunity, defense, nutrition and metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to
infection and prognosis. In current study we characterized the differences in gut bacterial communities in new tuberculosis patients (NTB), recurrent tuberculosis patients (RTB), and healthy control. The abundance-based coverage estimator (ACE) showed the diversity index of the gut microbiota in the patients with recurrent tuberculosis was increased significantly compared with healthy controls (
< 0.05). At the phyla level, Actinobacteria and Proteobacteria, which contain many pathogenic species, were significantly enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing a variety of beneficial commensal organisms, was reduced in the patients with the recurrent tuberculosis compared to healthy controls. The Gram-negative genus
of oral origin from phylum of Bacteroidetes and genus
from phylum of Firmicutes were significantly decreased in both the new and recurrent TB patient groups, compared with the healthy control group (
< 0.05). We also found that there was a positive correlation between the gut microbiota and peripheral CD4+ T cell counts in the patients. This study, for the first time, showed associations between gut microbiota with tuberculosis and its clinical outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be beneficial for host recovery and prevention of recurrence of
infection.
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