Search

Aims This study explores the plant growth-promoting effect (PGPE) and potential mechanisms of the arsenic (As)-resistant bacterium Flavobacterium sp. A9 (A9 hereafter). Methods and results The influences of A9 on the growth of Arabidopsis thaliana , lettuce, and Brassica napus under As(V) stress were investigated. Additionally, a metabolome analysis was conducted to unravel the underlying mechanisms that facilitate PGPE. Results revealed that A9 significantly enhanced the fresh weight of Arabidopsis seedlings by 62.6%–135.4% under As(V) stress. A9 significantly increased root length (19.4%), phosphorus (25.28%), chlorophyll content (59%), pod number (24.42%), and weight (18.88%), while decreasing As content (48.33%, P  ≤ .05) and oxidative stress of Arabidopsis. It also significantly promoted the growth of lettuce and B. napus under As(V) stress. A9 demonstrated the capability to produce ≥31 beneficial substances contributing to plant growth promotion (e.g. gibberellic acid), stress tolerance (e.g. thiamine), and reduced As accumulation (e.g. siderophores). Conclusions A9 significantly promoted the plant growth under As stress and decreased As accumulation by decreasing oxidative stress and releasing beneficial compounds. [ABSTRACT FROM AUTHOR]

In this study, based on the effect of compounds on the activation of NF-κB and NO release, compound 51 was discovered as the best one with NO release inhibition IC50 value was 3.1 ± 1.1 μM and NF-κB activity inhibition IC50 value was 172.2 ± 11.4 nM. Compound 51 could inhibit the activation of NF-κB through suppressing phosphorylation and nuclear translocation of NF-κB, and suppress LPS-induced inflammatory response in RAW264.7 cells, such as the over-expression of TNF-α and IL-6, which were target genes of NF-κB. This compound also showed preferable anti-inflammatory activity in vivo, including alleviating significantly gastric distention and splenomegaly caused by LPS stimulation, reducing the level of oxidative stress induced by LPS, and inhibiting the expression of IL-6 and TNF-α in serum. Thus, it's reasonable to consider that this compound is a promising small molecule with anti-inflammatory effect for inhibiting the NF-κB signalling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel CDK8 inhibitors were designed and synthesized. • The structure-based optimization and SAR study were fully carried out. • It augmented the abundance of IL-10 and showed potent effect against IBD. As an ideal anti-inflammatory target, cyclin-dependent kinase 8 (CDK8) has gradually attracted the attention of researchers. CDK8 inhibition up-regulates Interleukin-10 (IL-10) expression by enhancing the transcriptional activity of activator protein-1 (AP-1), and augmenting IL-10 abundance is a viable strategy for the treatment of inflammatory bowel disease (IBD). In this research, through structure-based drug design and dominant fragment hybridization, a series of poly-substituted pyridine derivatives were designed and synthesized as CDK8 inhibitors. Ultimately, compound CR16 was identified as the best one, which exhibited good inhibitory activity against CDK8 (IC 50 = 74.4 nM). In vitro and in vivo studies indicated that CR16 could enhance the transcriptional activity of AP-1, augment the abundance of IL-10, and affect CDK8-related signaling pathways including TLR7/NF-κB/MAPK and IL-10-JAK1-STAT3 pathways. In addition, CR16 showed potent therapeutic effect in an animal model of IBD. [ABSTRACT FROM AUTHOR]

Cyanobacterial blooms negatively affect aquatic ecosystems and human health. Algicidal bacteria can efficiently kill bloom-causing cyanobacteria. Bacillus altitudinis G3 isolated from Dianchi Lake shows high algicidal activity against Microcystis aeruginosa. In this study, we investigated its algicidal characteristics including attack mode, photosynthesis responses, and source and the contribution of reactive oxygen species (ROS). The results showed that G3 efficiently and specifically killed M. aeruginosa mainly by releasing both thermolabile and thermostable algicidal substances, which exhibited the highest algicidal activity (99.8%, 72 h) in bacterial mid-logarithmic growth phase. The algicidal ratio under full-light conditions (99.5%, 60 h) was significantly higher than under dark conditions (<20%, P < 0.001). G3 filtrate caused photosystem dysfunction by decreasing photosynthetic efficiency, as indicated by significantly decreased F v /F m and PI ABS (P < 0.001) values. It also inhibited photosynthetic electron transfer as indicated by significantly decreased rETR (P < 0.001), especially Q A − downstream, as revealed by significantly decreased φE o and ψ o , and increased M o (P < 0.001). These results indicated that the algicidal activity of G3 filtrate is light-dependent, and the cyanobacterial photosystem is an important target. Cyanobacterial ROS and malondialdehyde contents greatly increased by 37.1% and 208% at 36 h, respectively. ROS levels decreased by 49.2% (9 h) when diuron (3-(3-4-dichlorophenyl)-1,1-dimethylurea) partially blocked photosynthetic electron transport from Q A to Q B. Therefore, excessive ROS were produced from disrupted photosynthesis, especially the inhibited electron transport area in Q A − downstream, and caused severe lipid peroxidation with significantly increased MDA content and oxidative stress in cyanobacteria. The ROS scavenger N -acetyl- l -cysteine significantly decreased both cyanobacterial ROS levels (34%) and algicidal ratio (52%, P < 0.05) at 39 h. Thus, excessive ROS production due to G3 filtrate administration significantly contributed to its algicidal effect. G3 could be an excellent algicide to control M. aeruginosa blooms in waters under suitable light conditions. [Display omitted] • B. altitudinis G3 from Dianchi Lake bloom area is algicidal against M. aeruginosa. • Photosystem of M. aeruginosa as an important attack target of G3. • G3 decreased photosynthetic efficiency and inhibited electron transfer. • Dysfunctional photosystem results overproduction of reactive oxygen species. • Reactive oxygen species contributed to the algicidal effect of G3. [ABSTRACT FROM AUTHOR]

Cathepsin C (Cat C) is involved in inflammation regulation by activating neutrophil serine proteases (NSPs). Therefore, Cat C is an attractive target for treatment of inflammatory diseases mediated by NSPs overactivation. In previous study, compounds 54 and 77 were reported to be the first non-peptidyl non-covalent Cat C inhibitors, with good enzyme inhibitory activity and NSPs activation inhibition, but their pharmacokinetic (PK) properties were unsatisfactory. In this study, starting from 77 , after several rounds of structure-based design and modification, compound SF38 , a novel Cat C inhibitor bearing a unique thiophene structure was identified, which exhibited strong inhibitory activity against Cat C (IC 50 = 59.9 nM). Further mechanism study and in vivo evaluation showed that SF38 inhibited the Cat C activity in bone marrow and blood, decreased the activation of NSPs, and exhibited anti-inflammatory activity in an animal model of acute lung injury, with acceptable PK properties (F = 42.07%). These results enriched the structure-activity relationship (SAR) of Cat C inhibitor with thiophene structure characteristic, and proved the broad prospect of non-peptidyl non-covalent Cat C inhibitor. [Display omitted] • New Cathepsin C inhibitors were designed and synthesized. • The structure-based optimization and in vivo anti-acute lung injury study were fully carried out. • The results proved broad prospect of non-peptidyl non-covalent Cat C inhibitor. [ABSTRACT FROM AUTHOR]

[Display omitted] • New 4H-chromenone derivatives were designed and synthesized. • One compound should be alleviate mouse psoriasis. • The preliminary mechanism through JAK1/2-STAT1/3 pathway was discovered. On basis of Quercetin moiety, two series of 20 new compounds were designed and synthesized accordingly in this study, and their anti-inflammatory activities in vitro and in vivo were evaluated. At last, compound 8A2 : 3- (1- (2- (4- (5-bromo-2-chlorobenzoyl) piperazin-1-yl) ethyl)-1 H -1,2,3-triazol-4-yl) methoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4 H -chromen-4-one with low toxicity was found the best one for inhibiting of NO. Meanwhile, this compound could significantly inhibit the expression of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-α) and IL-17 (Interleukin-17), and also significantly down-regulate IL-17 mRNA psoriasis model in vitro. Further studies were performed to establish mouse psoriasis model induced by Imiquimod (IMQ), and the preliminary mechanism indicated that compound 8A2 may alleviate mouse psoriasis through obstructed the JAK1/2-STAT1/3 pathway. This study should be provide a basis for further study of effective treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Click-through rate is a central issue in ad recommendation and has recently received extensive research attention in academia and industry. Research shows that the accuracy of prediction results in CTR prediction is closely related to interactive features and user interest features. However, existing models usually focus on one aspect of features, i.e., interactive features or interest features, and few studies have attempted to learn both interactive features and interest features simultaneously. In this paper, a novel model called CFF as an abbreviation for Combining interactive Features and interest Features is proposed to learn interactive features and user interest features simultaneously. To efficiently learn fine-grained interactive features, an attention-based squeeze equal interaction network (ASENet) is constructed to select salient feature information at the level of equal interactive features. A bi-directional attention-target item gated recurrent unit (Bi-ATGRU) is designed to learn the dependencies between user interests and items. Specifically, it refines and integrates interest features by incorporating context information, historical behaviors, and target item. Extensive experiments on four public datasets indicate CFF outperforms other baselines in terms of evaluation metrics (the Logloss decreases by 1.97% on Frappe and 1.85% on MovieLens). [ABSTRACT FROM AUTHOR]

Keyphrase Extraction is an automatic task that involves identifying the key words or phrases that capture the main content of an article. It is useful for various downstream tasks, including text search, text clustering, and text classification. Embedding-based methods for keyphrase extraction have shown promising results by utilizing pre-trained language models to represent candidate phrases and documents separately. These methods then rank the candidate phrases based on the cosine similarity between the document and the candidate phrases embeddings. However, there are mainly two shortcomings in such methods: I) Redundancy errors, when there are partial repetitions of candidate keyphrases, the methods tend to use redundant long phrases as keyphrases; II) Low keyphrase coverage, such as some keyphrases used to describe locally important information are ignored. In this paper, we propose an unsupervised keyphrase extraction method called "MICRank", which evaluates the importance of candidate keyphrases from three perspectives: global information, local information, and attribute information, and solved the aforementioned issues. The experimental results on six benchmarks demonstrate that the proposed MICRank method outperforms the state-of-the-art unsupervised keyphrase extraction methods. In addition, this paper improves the judgment criterion of correct keyphrase extraction and introduces a new evaluation metric called S1@M (M ∈ {5,10,15}) to address the issue of synonyms being considered incorrect predictions. [ABSTRACT FROM AUTHOR]

Bone marrow-derived mesenchymal stem cells (BMSCs) have recently been introduced to treat cardiovascular diseases, such as myocardial infarction and dilated cardiomyopathy. Nevertheless, there are few researches focused on the application of BMSCs in treating viral myocarditis, not to mention its optimal intervention timer potential mechanisms. In our study, we concentrated on finding an optimal time window to perform BMSCs treatment in a murine model of myocarditis induced by coxsackievirus B3 (CVB3). On the 1st day, 3rd day, 7th day, and 14th day after BALB/c mice were infected by CVB3, we intravenously injected equivalent BMSCs into the treatment groups. With a 28-day follow-up after inoculation, we found that the ventricular function was significantly improved in the BMSCs treatment group and cardiac fibrosis markedly ameliorated, especially when BMSCs were injected between 1 and 2 weeks after CVB3 inoculation. Furthermore, we demonstrated that after BMSCs treatment, the expressions of TGF-β, col1α1, and col3α1 were significantly decreased. Therefore, we conclude that BMSCs may have a potential to improve CVB3-induced myocarditis by ameliorating cardiac fibrosis through the inhibition of TGF-β expression. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 8 (CDK8) plays an momentous role in transcription regulation by forming kinase module or transcription factor phosphorylation. A large number of evidences have identified CDK8 as an important factor in cancer occurrence and development. In addition, CDK8 also participates in the regulation of cancer cell stress response to radiotherapy and chemotherapy, assists tumor cell invasion, metastasis, and drug resistance. Therefore, CDK8 is regarded as a promising target for cancer therapy. Most studies in recent years supported the role of CDK8 as a carcinogen, however, under certain conditions, CDK8 exists as a tumor suppressor. The functional diversity of CDK8 and its exceptional role in different types of cancer have aroused great interest from scientists but even more controversy during the discovery of CDK8 inhibitors. In addition, CDK8 appears to be an effective target for inflammation diseases and immune system disorders. Therefore, we summarized the research results of CDK8, involving physiological/pathogenic mechanisms and the development status of compounds targeting CDK8, provide a reference for the feasibility evaluation of CDK8 as a therapeutic target, and guidance for researchers who are involved in this field for the first time. Image 1 • Physiological and pathological functions of CDK8 and its chaperones were reviewed. • Design strategies for CDK8-targeted compounds were proposed. • CDK8 inhibitors were reviewed. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is one of the leading causes of morbidity and mortality in diabetic patients. Piceatannol (PIC) has protective effects against cardiovascular disease; however, it remains unknown whether it also protects against DCM. A Cell Counting Kit-8 (CCK-8) assay was used to evaluate the effects of PIC on the viability of high glucose (HG)-induced H9C2 cells. Protein expression and mRNA levels were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. In vivo, physical and biochemical analyses, together with transthoracic echocardiography and hemodynamic measurements, were used to detect the effects of PIC treatment on cardiac function in DCM rats. Reactive oxygen species production was determined using an ELISA kit, and inflammatory cytokines were detected by RT-PCR. Pathological changes were assessed by hematoxylin-eosin staining, immunohistochemical staining, and TUNEL staining. According to the results, PIC treatment improved cell viability and inhibited cell apoptosis in HG-induced H9C2 cardiac myoblasts. In addition, PIC not only attenuated the over-production of interleukin-6 (IL-6) (P < 0.05) and tumor necrosis factor alpha (TNF-α) (P < 0.05), but also improved the expression of nuclear factor E2-related factor 2 (Nrf2) (P < 0.05) and heme oxygenase-1 (HO-1) (P < 0.01). Importantly, knockdown of Nrf2 suppressed PIC-mediated activation of the Nrf2/HO-1 pathway and abolished its anti-inflammatory effects. In vivo, oral administration of PIC suppressed STZ-induced inflammation, oxidative stress hypertrophy, fibrosis(myocardial collagen volume fraction in 5 mg/kg and 10 mg/kg PIC group was decreased 25.83% and 55.61% compared with the DM group), and apoptosis(Caspase-3 level in 5 mg/kg and 10 mg/kg PIC group was decreased 13.21% and 33.91% compared with the DM group), thereby relieving cardiac dysfunction and improving both fibrosis and pathological changes in cardiac tissues of diabetic rats. These findings define for the first time that the effects of PIC against DCM can be attributed to its role in inflammation and oxidative stress inhibition. • PIC inhibits cell apoptosis by reducing oxidative stress and inflammation. • The pic-mediated suppression of NF-κB activation is dependent on Nrf2. • PIC improves the cardiac function of DCM rats. • PIC suppresses diabetes-induced cardiac oxidative stress and inflammation. • PIC can be a promising and safe agent for the treatment of DCM. [ABSTRACT FROM AUTHOR]