Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist

The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy

Perceptual Quality Assessment of Omnidirectional Audio-visual Signals

Omnidirectional videos (ODVs) play an increasingly important role in the application fields of medical, education, advertising, tourism, etc. Assessing the quality of ODVs is significant for service-providers to improve the user's Quality of Experience (QoE). However, most existing quality assessment studies for ODVs only focus on the visual distortions of videos, while ignoring that the overall QoE also depends on the accompanying audio signals. In this paper, we first establish a large-scale audio-visual quality assessment dataset for omnidirectional videos, which includes 375 distorted omnidirectional audio-visual (A/V) sequences generated from 15 high-quality pristine omnidirectional A/V contents, and the corresponding perceptual audio-visual quality scores. Then, we design three baseline methods for full-reference omnidirectional audio-visual quality assessment (OAVQA), which combine existing state-of-the-art single-mode audio and video QA models via multimodal fusion strategies. We validate the effectiveness of the A/V multimodal fusion method for OAVQA on our dataset, which provides a new benchmark for omnidirectional QoE evaluation. Our dataset is available at https://github.com/iamazxl/OAVQA.Comment: 12 pages, 5 figures, to be published in CICAI202

Coordinated changes in mRNA turnover, translation, and RNA processing bodies in bronchial epithelial cells following inflammatory stimulation.

Bronchial epithelial cells play a pivotal role in airway inflammation, but little is known about posttranscriptional regulation of mediator gene expression during the inflammatory response in these cells. Here, we show that activation of human bronchial epithelial BEAS-2B cells by proinflammatory cytokines interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) leads to an increase in the mRNA stability of the key chemokines monocyte chemotactic protein 1 and IL-8, an elevation of the global translation rate, an increase in the levels of several proteins critical for translation, and a reduction of microRNA-mediated translational repression. Moreover, using the BEAS-2B cell system and a mouse model, we found that RNA processing bodies (P bodies), cytoplasmic domains linked to storage and/or degradation of translationally silenced mRNAs, are significantly reduced in activated bronchial epithelial cells, suggesting a physiological role for P bodies in airway inflammation. Our study reveals an orchestrated change among posttranscriptional mechanisms, which help sustain high levels of inflammatory mediator production in bronchial epithelium during the pathogenesis of inflammatory airway diseases

Medicarpin induces G1 arrest and mitochondria-mediated intrinsic apoptotic pathway in bladder cancer cells

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study revealed that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy

High-temperature modification of steel slag using composite modifier containing silicon calcium slag, fly ash, and reservoir sediment

Steel slag (SS) is a kind of industrial solid waste, and its accumulation brings certain harm to the ecological environment. In order to promote the building material utilization of SS, high-temperature modification (HTM) of SS is performed using a composite modifier (CMSFR) containing silicon calcium slag (SCS), fly ash (FA), and reservoir sediment (RS). Then, the authors investigated the effect of CMSFR on the cementitious properties and volume soundness of SS mixture after HTM (SMHTM). After that, the mineral composition and microstructure of SMHTM were investigated through X-ray fluorescence analysis (XRF), X-ray diffraction (XRD), scanning electronic microscopy (SEM), energy dispersive spectrometry (EDS), and particle size analysis. It was found that the free CaO (f-CaO) content obviously decreased, and the cementitious properties improved in SMHTM. When the CMSFR content was 20% (SCS: FA: RS = 9:7:4), and the modification temperature (MT) was 1,250°C, the mass fraction of f-CaO in SMHTM dropped from 4.81% to 1.90%, down by 60.5%; the 28-day activity index of SMHTM increased to 85.4%, 14.3% higher than that of raw SS, which meets the technical requirement of Steel slag powder used for cement and concrete (GB/T 20491-2017): the activity index of grade I SS powder must be greater than or equal to 80%. As the mass fraction of CMSFR grew from 10% to 30%, new mineral phases formed in SMHTM, including diopside (CMS2), ceylonite (MgFe2O4), gehlenite (C2AS), tricalcium aluminate (C3A), and magnetite (Fe3O4). The HTM with CMSFR promotes the decomposition of RO phase (a continuous solid solution composed of divalent metal oxides like FeO, MgO, MnO, and CaO) in raw SS, turning the FeO in that phase into Fe3O4. The above results indicate that the SMHTM mixed with CMSFR can be applied harmless in cement and concrete, making low-energy fine grinding of SS a possibility

Research on the biological mechanism and potential application of CEMIP

Cell migration–inducing protein (CEMIP), also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the hyaluronidase family that degrades hyaluronic acid (HA) and remodels the extracellular matrix. In recent years, some studies have reported that CEMIP can promote the proliferation, invasion, and adhesion of various tumor cells and can play an important role in bacterial infection and arthritis. This review focuses on the pathological mechanism of CEMIP in a variety of diseases and expounds the function of CEMIP from the aspects of inhibiting cell apoptosis, promoting HA degradation, inducing inflammatory responses and related phosphorylation, adjusting cellular microenvironment, and regulating tissue fibrosis. The diagnosis and treatment strategies targeting CEMIP are also summarized. The various functions of CEMIP show its great potential application value

Immune cell early activation, apoptotic kinetic, and T-cell functional impairment in domestic pigs after ASFV CADC_HN09 strain infection

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV

Association of Adiponectin SNP+45 and SNP+276 with Type 2 Diabetes in Han Chinese Populations: A Meta-Analysis of 26 Case-Control Studies

Recently, many studies have reported that the SNP+45(T>G) and SNP+276(G>T) polymorphisms in the adiponectin gene are associated with type 2 diabetes (T2DM) in the Chinese Han population. However, the previous studies yielded many conflicting results. Thus, a meta-analysis of the association of the adiponectin gene with T2DM in the Chinese Han population is required. In the current study, we first determined the distribution of the adiponectin SNP+276 polymorphism in T2DM and nondiabetes (NDM) control groups. Our results suggested that the genotype and allele frequencies for SNP+276 did not differ significantly between the T2DM and NDM groups. Then, a meta-analysis of 23 case-control studies of SNP+45, with a total of 4161 T2DM patients and 3709 controls, and 11 case-control studies of SNP+276, with 2533 T2DM patients and 2212 controls, was performed. All subjects were Han Chinese. The fixed-effects model and random-effects model were applied for dichotomous outcomes to combine the results of the included studies. The results revealed a trend towards an increased risk of T2DM for the SNP+45G allele as compared with the SNP+45T allele (OR = 1.34; 95% CI, 1.11–1.62; P<0.01) in the Chinese Han population. However, there was no association between SNP+276 and T2DM (OR = 0.90; 95% CI, 0.73–1.10; P = 0.31). The results of our association study showed there was no association between the adiponectin SNP+276 polymorphism and T2DM in the Yunnan Han population. The meta-analysis results suggested that the SNP+45G allele might be a susceptibility allele for T2DM in the Chinese Han population. However, we did not observe an association between SNP+276 and T2DM