Search

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]

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]

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]