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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]

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]

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]

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]

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% to 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 ≤ 0.05) 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Objective: Analyzing the impact of nursing workforce development, training and standardization on hybrid operating theatres., Methods: Thirty nurses in the mixed operating room of the First Affiliated Hospital of Nanchang University from January 2021 to December 2021 were selected as the control group to receive routine nursing management and training methods and another thirty nurses were selected as the experimental group to receive nursing team construction, training and standardized management based on conventional methods. Nurses' theoretical and operational scores, nurses' satisfaction, surgeon satisfaction with nurses, and nursing service quality scores were compared between two groups at baseline and after intervention., Results: After the intervention, nurses in both groups had a significant improvement in theoretical and operational scores than those at baseline, and nurses in the experimental group had better scores than those in the control group, The difference was statistically significant (P = .002, P = .004). Nursing quality of surgical preparation, environmental management, surgical safety, and instrument management in the intervention group were significantly better than those at baseline and better than those in the control group. The difference was statistically significant (P = .001, P = .001, P = .001, P = .001). Satisfaction of nurses and doctors in the intervention group was significantly better than those at baseline and better than those in the control group. The difference was statistically significant (P = .002, P = .001)., Conclusion: The effect of nursing team construction and training and standardized management of hybrid operating Room was ideal, which can improve nurses' theoretical knowledge and practical skills, and enhance the satisfaction of nurses and surgeons, providing patients with higher quality nursing services, which is worth adopting.

It is significant to design, synthesise and optimise flavonoid derivatives with better anti-inflammatory activity. This study aims to design and synthesise a series of novel 2-phenyl-4H-chromen-4-one compounds with anti-inflammatory; among them, compound 8 was discovered as the best one. And then, the effects of compound 8 on the TLR4/MAPK signalling pathway was carried out in vivo , the results indicated that compound 8 could downregulate NO, IL-6, and TNF-α expression, and suppress LPS-induced inflammation by inhibiting the TLR4/MAPK pathways. Furthermore, compound 8 reduced inflammation by a mouse model of LPS-induced inflammatory disease in vivo . The results suggest that compound 8 has the potential against inflammation through regulating TLR4/MAPK pathway and can be assessed further for drug development.

Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent "non-peptidyl non-covalent cathepsin C inhibitor" was described with hit finding, structure optimization, and lead discovery. Starting with hit 14 , structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro . Also, compound 54 (with cathepsin C Enz IC 50 = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding.

Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro- N 4 -phenyl- N 2 -(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.

We investigated the expression of caveolin-1 (Cav-1) in Kawasaki disease (KD) and analyzed its relationship with coronary artery lesions (CALs). Cav-1 participated in the progression of CAL in KD. A total of 68 children with KD (23 with CALs), age matched with a fever control group (F, n = 28) and a normal control group (N, n = 24) were enrolled in this study. Cav-1 expression was detected using an enzyme-linked immunosorbent assay. The results are the following: (1) Compared with the F and N, Cav-1 expression was significantly increased in the children with KD (P < 0.05); there was no significant difference in Cav-1 between the F and N. (2) The serum level of Cav-1 was significantly higher in children with KD and CALs during the acute phase than in children with KD without CALs (P < 0.05). (3) Serum Cav-1 may be a biomarker that reflects CALs in children with KD based on a receiver operating characteristic (ROC) curve analysis. (4) Those children with KD who were given intravenous immunoglobulin (2 g/kg, 10-12 h) during the acute phase showed decreased expression of Cav-1 compared to the N. Conclusions are as follows: (1) The serum level of Cav-1 during the acute phase of KD increased significantly, while in KD patients with CALs the increase was even greater. (2) Based on our ROC curve analysis, Cav-1 may be a predictor of CALs in children with KD., Competing Interests: None

Background: Cardiomyocyte apoptosis is critical for the development of coxsackievirus B3- (CVB3-) induced myocarditis, which is a common cardiac disease that may result in heart failure or even sudden death. Previous studies have associated CVB3-induced apoptosis with the downregulation of antiapoptotic proteins. Here, attempts were made to examine whether nicotinic acetylcholine receptors (nAChRs), especially α 3 β 4-nAChRs, were a novel therapeutic antiapoptotic target via the activation of survivin, a strong antiapoptotic protein, in viral myocarditis (VMC)., Methods and Results: In the present study, we demonstrated that nAChRs, α 3 β 4-nAChR subunits in particular, were present and upregulated in CVB3-infected neonatal rat cardiomyocytes (NRC) and H9c2 cells by RT-qPCR. The function of α 3 β 4-nAChRs was next examined using its specific blocker α -CTX AuIB in vitro. The results of the TUNEL assay and western blot experiments showed that the block of α 3 β 4-nAChRs abrogated nicotine-mediated protection of NRC from CVB3-induced apoptosis, and this effect displayed a substantial correlation with the protein expressions of pAkt, survivin, and Cleaved Caspase-3. Hence, the involvement of the PI3K/Akt pathway was further verified by LY294002, a selective inhibitor of PI3K. As a result, nicotine-mediated induction of pAkt and survivin was abolished by LY294002; meanwhile, apoptotic NRC were increased accompanied by an increase of Cleaved Caspase-3 expression. Regarding CVB3-infected BALB/c mice, the α -CTX AuIB- and LY294002-treated groups had a lower survival rate, deteriorative ventricular systolic function, and more severe inflammation than the nicotine-treated group and the modulation of pAkt, survivin, and Cleaved Caspase-3 protein expressions was similar to that in CVB3-infected NRC. In addition, we found that a nicotinic agonist reduced CVB3 replication in a dose-dependent manner in vitro, which indicates that nAChR activation may serve as a possible protection mechanism of CVB3-induced myocarditis., Conclusions: Our study demonstrated that α 3 β 4-nAChR subunits are essential in the nicotine-mediated antiapoptotic effect of protecting cardiomyocytes from CVB3-induced apoptosis in vivo and in vitro. This protection correlated with the PI3K/Akt pathway and the inducement of the antiapoptotic protein survivin. A combination of these mechanisms serves as a novel protective response to treat viral myocarditis.

Creativity is related to both cognition and emotion, which are the two major mental processes, interacting with each other to form psychological processes. Emotion is the major driving force of almost all creativities, sometimes in an unconscious way. Even though there are many studies concerning the relationship between creativity and cognition, there are few studies about the neural mechanisms of the emotional effects on creativity. Here, we introduce a novel model to explain the relationship between emotions and creativities: Three Primary Color model , which proposes that there are four major basic emotions; these basic emotions are subsided by three monoamines, just like the three primary colors: dopamine-joy, norepinephrine-stress (fear and anger), and serotonin-punishment. Interestingly, these three neuromodulators play similar roles in creativity, whose core features are value and novelty (surprise), like the characteristics of the core features of basic emotions (hedonic value and arousal value). Dysfunctions of these neuromodulators may be the reasons for both psychopathology and creativity, in that they can change the thinking styles such as novelty seeking behavior, hyper-connectivity of brain areas, and/or cognitive disinhibition to induce both creativity and psychopathology. This new model will not only help researchers understand the dynamics of basic emotion elements, it can also bring an entirely new perspective into the relationship between psychopathology and creativity.