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Three novel ent-kaurane diterpenes, namely sigesbeckin A–C (1–3), in conjunction with eight previously identified analogues (4–11), were isolated from Sigesbeckia orientalis. Their chemical structures were resolved through multiple spectroscopic analyses. All compounds were assessed for antimicrobial bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. In particular, compounds 1 and 5 demonstrated moderate efficacy, with MIC values of 64 μg/mL. Moreover, compounds 3, 5, and 11 were found to synergize with doxorubicin hydrochloride (DOX) and vancomycin (VAN) against MRSA and VRE. The aforementioned findings offer valuable insights for the development of novel alternatives to antibiotics, which can effectively tackle the escalating issue of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)‐based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation‐related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM‐inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc− (a cystine/glutamate antiporter). After adding cystine to CM‐based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages. [ABSTRACT FROM AUTHOR]

Excessive ultraviolet (UV) exposure can lead to sunburn, characterized by skin barrier damage, inflammation, pain, and an increased risk of skin cancer. Recombinant collagens have gradually attracted attention due to their high purity, low immunogenicity, batch-to-batch consistency, and excellent solubility. Additionally, the type of dressing significantly affects wound repair. Gels are ideal for sunburn treatment because they maintain a moist environment, adhere firmly, and do not need to be removed. Herein, we have created bioactive triple-helical recombinant collagen (THRC) gels for improved healing of sunburned skin. The THRC gels remained stable after a three-month stability test, displaying a rheological behavior characteristic of non-Newtonian pseudoplastic fluids. In vivo skin irritation tests conducted on New Zealand rabbits demonstrated that THRC gels were safe for use. A sunburned mice model was established to study the biological effects of THRC gels. Non-invasive combo evaluations indicated that THRC gels exhibited an exceptional capability of recovering dermis density, erythema index (EI), hydration, and transepidermal water loss (TEWL) of sunburned skin to a healthy state. Histological observations revealed that THRC gels significantly enhanced the repair of damaged skin by accelerating the recovery process, promoting collagen deposition and regeneration. Molecular biological characterizations further demonstrated their remarkable antioxidant properties, including the inhibition of lipoperoxidation and the enhancement in superoxide dismutase (SOD) and glutathione (GSH) activities. These safe and bioactive recombinant collagen gels provide a novel approach for sunburn repair and show potential for long-term cosmetic benefits. [ABSTRACT FROM AUTHOR]

This research aimed to evaluate the therapeutic effect of corilagin (Cor) against angiotensin II (Ang II)-induced cardiac fibrosis and its underlying mechanisms. C57BL/6 mice (male, 8-10 weeks) received saline or Ang II (2.0 mg/kg/day) via subcutaneous infusion and intraperitoneal injection of Cor (30 mg/kg) for 28 days. Ang II induction increased the fibrotic area, whereas Cor treatment inhibited the fibrotic area significantly. Cor markedly reduced the Ang II-induced cardiac fibroblasts. Cor significantly inhibited Ang II-induced increase in expressions of smooth muscle alpha-actin (α-SMA), collagen I, collagen III, transforming growth factor beta 1 (TGF-β1), fibronectin, and connective tissue growth factor (CTGF). Cor suppressed the intracellular reactive oxygen species (ROS) production. Cor therapy reduced Ang II-induced malondialdehyde (MDA) content, whereas superoxide dismutase (SOD) and catalase (CAT) activities were increased (all, P <.001). Moreover, Ang II induction elevated the expression of phosphorylated phosphatase and tensin homolog (p-PTEN), phosphorylated protein kinase B (p-AKT) (Ser473) and phosphorylated mammalian target of rapamycin (p-mTOR) (Ser 2448), whereas Cor reduced their expressions. Cor treatment inhibited the migration ability of the cardiac fibroblast, whereas a PTEN inhibitor, VO-ohpic, increased the migration capability. Cor could have a protective effect against Ang II-induced cardiac fibrosis via inhibition of the PTEN/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g., stress relaxation) during periodontitis or dental trauma, which disrupt cell–extracellular matrix (ECM) interactions and accelerates tissue damage. Here, Pluronic F127 diacrylate (F127DA) hydrogels with PDL‐matched stress relaxation rates and high elastic moduli are developed. The hydrogel viscoelasticity is modulated without chemical cross‐linking by controlling precursor concentrations. Under cytomechanical loading, F127DA hydrogels with fast relaxation rates significantly improved the fibrogenic differentiation potential of PDL stem cells (PDLSCs), while cells cultured on F127DA hydrogels with various stress relaxation rates exhibited similar fibrogenic differentiation potentials with limited cell spreading and traction forces under static conditions. Mechanically, faster‐relaxing F127DA hydrogels leveraged cytomechanical loading to activate PDLSC mechanotransduction by upregulating integrin–focal adhesion kinase pathway and thus cytoskeletal rearrangement, reinforcing cell–ECM interactions. In vivo experiments confirm that faster‐relaxing F127DA hydrogels significantly promoted PDL repair and reduced abnormal healing (e.g., root resorption and ankyloses) in delayed replantation of avulsed teeth. This study firstly investigated how matrix nonlinear viscoelasticity influences the fibrogenesis of PDLSCs under mechanical stimuli, and it reveals the underlying mechanobiology, which suggests novel strategies for PDL regeneration. [ABSTRACT FROM AUTHOR]

With the development of energy transition, the complexity of power systems’ structure, planning and operation is continuously increasing. As to quickly and accurately assess the dynamic security region of power system, there are prominent problems with traditional manual analysis method, i.e. the rules’ roughness and a low calculation efficiency while data mining approach could provide a new way to get off such problems. Considering that the performance of SVM algorithm depends on feature selection and the LightGBM, a fast and efficient classification algorithm, can be used for feature selection, this paper proposes a new algorithm based on a fusion model. With the CEPRI-36 bus power system, the results of different algorithms are compared and the proposed algorithm verified.

Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored. It was found that exposure of PDLSCs to abundant PA led to decreased cell osteogenic differentiation. Given that long non‐coding RNAs (lncRNAs) play a key role in the stem cell response to adverse environmental stimuli, we screened the lncRNAs that were differentially expressed in PDLSCs following PA exposure using lncRNA microarray analysis, and AC018926.2 was identified as the lncRNA that was most sensitive to PA. Next, gain/loss‐of‐function studies illustrated that AC018926.2 was an important regulator in PA‐mediated osteogenic differentiation of PDLSCs. Mechanistically, AC018926.2 upregulated integrin α2 (ITGA2) expression and therefore activated ITGA2/FAK/AKT signalling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signalling by silencing ITGA2 counteracted the pro‐osteogenic effect induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and RNA immunoprecipitation assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to PARP1 protein. Our data suggest that AC018926.2 may serve as a therapeutic target for the management of periodontitis in obese patients. [ABSTRACT FROM AUTHOR]

In order to study the influence of the replacement ratio of recycled aggregate and the volume of waste fiber on the fracture performance of concrete, the three-point bending test is carried out on the waste fiber recycled concrete precast beams. Calculate the waste recycled fiber concrete fracture parameters according to the double-K fracture model. The results show that the fracture indexes of recycled fiber are related to the recycled aggregate replacement ratio and the volume content of waste fiber. The larger the replacement rate of recycled aggregate is, the smaller the fracture indexes of the specimens are. The volume content of waste fiber is 0.12%, which has the most significant effect on the fracture performance. The study shows that waste fiber can improve the fracture properties of recycled aggregate concrete.