Integrating network pharmacology and experimental evaluation to explore the complementary therapeutic effect and mechanism of melatonin in periodontitis.

Objective: To explore the potential targets for melatonin in the treatment of periodontitis through network pharmacologic analysis and experimental validation via in vivo animal models and in vitro cellular experiments. Materials and methods: In this study, we first screened melatonin targets from Pharm Mapper for putative targets, Drug Bank, and TCMSP databases for known targets. Then, disease database was searched and screened for differential expressed genes associated with periodontitis. The intersection of disease and melatonin-related genes yielded potential target genes of melatonin treatment for periodontitis. These target genes were further investigated by protein-protein interaction network and GO/KEGG enrichment analysis. In addition, the interactions between melatonin and key target genes were interrogated by molecular docking simulations. Then, we performed animal studies to validate the therapeutic effect of melatonin by injecting melatonin into the peritoneal cavity of ligation-induced periodontitis (LIP) mice. The effects of melatonin on the predicted target proteins were also analyzed using Western blot and immunofluorescence techniques. Finally, we constructed an in vitro cellular model and validated the direct effect of melatonin on the predicted targets by using qPCR. Results: We identified 8 potential target genes by network pharmacology analysis. Enrichment analysis suggests that melatonin may treat periodontitis by inhibiting the expression of three potential targets (MPO, MMP8, and MMP9). Molecular docking results showed that melatonin could effectively bind to MMP8 and MMP9. Subsequently, melatonin was further validated in a mouse LIP model to inhibit the expression of MPO, MMP8, and MMP9 in the periodontal tissue. Finally, we verified the direct effect of melatonin on the mRNA expression of MPO, MMP8, and MMP9 in an in vitro cellular model. Conclusions: Through a combination of network pharmacology and experimental validation, this study provides a more comprehensive understanding of the mechanism of melatonin to treat periodontitis. Our study suggests that MPO, MMP8, and MMP9 as key target genes of melatonin to treat periodontitis. These findings present a more comprehensive basis for further investigation into the mechanisms of pharmacological treatment of periodontitis by melatonin.

Autonomous indication of electrical degradation in polymers.

Dielectric polymers are ubiquitous as electrical insulation in electronic devices and electrical systems. Electrical degradation of dielectric polymers tends to initiate catastrophic failure of numerous devices and systems, but its detection and early warning remain challenging. Here we report a general material strategy that signals the electrical degradation of dielectric polymers by autonomously presenting a visually discernible warning in the form of a pronounced colour change. This colour change is induced by the chromogenic response of molecular indicators blended with the polymer, which are chemically activated by the oxygen radicals generated in situ during the electrical degradation of the polymer. We unveil that the structural degradation and electrical properties of the dielectric polymer are quantitatively correlated with the colour difference. Such a chromogenic process is autonomous without the need of human intervention or other external energy, thus offering the convenience to lower or even eliminate the risk of dielectric failure.

Long Cycle Life for Rechargeable Lithium Battery using Organic Small Molecule Dihydrodibenzo[c,h][2,6]naphthyridine-5,11-dione as a Cathode after Isoindigo Pigment Isomerization.

Sustainability and adaptability in structural design of the organic cathodes present promises for applications in alkali metal ion batteries. Nevertheless, a formidable challenge lies in their high solubility in organic electrolytes, particularly for small molecular materials, impeding cycling stability and high capacity. This study focuses on the design and synthesis of organic small molecules, the isomers of (E)-5,5'-difluoro-[3,3'-biindolinylidene]-2,2'-dione (EFID) and 3,9-difluoro-6,12-dihydrodibenzo [c, h][2,6]naphthyridine-5,11-dione (FBND). While EFID, characterized by a less π-conjugated structure, exhibits subpar cycling stability in lithium-ion batteries (LIBs), intriguingly, another isomer, FBND, demonstrates exceptional capacity and cycling stability in LIBs. FBND delivers a remarkable capacity of 175 mAh g-1 at a current density of 0.05 A g-1 and maintains excellent cycling stability over 2000 cycles, retaining 90% of its initial capacity. Furthermore, an in-depth examination of redox reactions and storage mechanisms of FBND are conducted. The potential of FBND is also explored as an anode in lithium-ion batteries (LIBs) and as a cathode in sodium-ion batteries (SIBs). The FBND framework, featuring extended π-conjugated molecules with an imide structure compared to EFID, proves to be an excellent material template to develop advanced organic small molecular cathode materials for sustainable batteries.

Quercetin promotes autophagy to alleviate cigarette smoke-related periodontitis.

BACKGROUND AND OBJECTIVES: Cigarette smoking has been reported as an independent risk factor for periodontitis. Tobacco toxins affect periodontal tissue not only locally but also systemically, leading to the deterioration and recurrence of periodontitis. However, the mechanism of cigarette smoke-related periodontitis (CSRP) is unclear and thus lacks targeted treatment strategies. Quercetin, a plant-derived polyphenolic flavonoid, has been reported to have therapeutic effects on periodontitis due to its documented antioxidant activity. This study aimed to evaluate the effects of quercetin on CSRP and elucidated the underlying mechanism. METHODS: The cigarette smoke-related ligature-induced periodontitis mouse model was established by intraperitoneal injection of cigarette smoke extract (CSE) and silk ligation of bilateral maxillary second molars. Quercetin was adopted by gavage as a therapeutic strategy. Micro-computed tomography was used to evaluate the alveolar bone resorption. Immunohistochemistry detected the oxidative stress and autophagy markers in vivo. Cell viability was determined by Cell Counting Kit-8, and oxidative stress levels were tested by 2,7-dichlorodihydrofluorescein diacetate probe and lipid peroxidation malondialdehyde assay kit. Alkaline phosphatase and alizarin red staining were used to determine osteogenic differentiation. Network pharmacology analysis, molecular docking, and western blot were utilized to elucidate the underlying molecular mechanism. RESULTS: Alveolar bone resorption was exacerbated and oxidative stress products were accumulated during CSE exposure in vivo. Oxidative stress damage induced by CSE caused inhibition of osteogenic differentiation in vitro. Quercetin effectively protected the osteogenic differentiation of human periodontal ligament cells (hPDLCs) and periodontal tissue by upregulating the expression of Beclin-1 thus to promote autophagy and reduce oxidative stress damage. CONCLUSION: Our results established a role of oxidative stress damage and autophagy dysfunction in the mechanism of CSE-induced destruction of periodontal tissue and hPDLCs, and provided a potential application value of quercetin to ameliorate CSRP.

Spiral-Structured Dielectric Polymers Exhibiting Ultrahigh Energy Density and Charge-Discharge Efficiency at High Temperatures.

The growing need for high-power and compact-size energy storage in modern electronic and electrical systems demands polymer film capacitors with excellent temperature capability. However, conventional polymer dielectrics feature dramatic deterioration in capacitive performance under concurrent high temperature and electric field because the high thermal stability traditionally relies on the conjugated, planar molecular segments in the polymer chains. Herein, inspired by the stable double helix structures of deoxyribonucleic acid, spiral-structured dielectric polymers that exhibit simultaneous high thermal stability and great capacitive performance are demonstrated. Both the experimental results and computational simulations confirm that the spiral groups serve to weaken the electrostatic molecular interaction, induce proper molecular chain stacking structure, and regulate the charge transfer process by breaking the conjugated planes and introducing deep trap sites. The resultant polymer exhibits the maximum discharged energy densities of 7.29 and 6.13 J cm-3 with the charge-discharge efficiency above 90% at 150 and 200 °C, respectively, more than ten times those of the original dielectric at the same conditions. Here a completely new dimension is offered for the molecular design of polymers, giving rise to well-balanced thermal and dielectric properties, and ultimately the desired capacitive energy storage performance at high temperatures.

A Bi-Gradient Dielectric Polymer/High-Κ Nanoparticle/Molecular Semiconductor Ternary Composite for High-Temperature Capacitive Energy Storage.

Attaining compact energy storage under extreme temperature conditions is of paramount importance in the development of advanced dielectric materials. The polymer composite approach has proved effective towards this goal, and addressing the correlation between filler distribution and electrical properties is foremost in designing composite dielectrics, especially in multifiller systems. Here, the design of a bi-gradient polymer composite dielectric using an integrated framework based on the phase field model is reported. This framework can predict the charge-inhibiting behavior of composite dielectrics, which is a key factor impacting the high-temperature capacitive performance but unfortunately is ignored in conventional phase field models. It is found that due to the traps provided by the functional organic fillers, more carriers are trapped near the electrodes and weaken the electric field, thus significantly suppressing the breakdown initialization process. An interpenetrating gradient structure is designed rationally and synthesized experimentally, which exhibits concurrent high energy density (5.51 J cm-3 ) and high charge-discharge efficiency (90%) up to 200 °C. This work provides a strategy to predict the high-temperature energy storage performance of polymer composites containing charge-inhibiting components and helps broaden the scope of data-driven materials design based on phase-field modeling.

Designing tailored combinations of structural units in polymer dielectrics for high-temperature capacitive energy storage.

Many mainstream dielectric energy storage technologies in the emergent applications, such as renewable energy, electrified transportations and advanced propulsion systems, are usually required to operate under harsh-temperature conditions. However, excellent capacitive performance and thermal stability tend to be mutually exclusive in the current polymer dielectric materials and applications. Here, we report a strategy to tailor structural units for the design of high-temperature polymer dielectrics. A library of polyimide-derived polymers from diverse combinations of structural units are predicted, and 12 representative polymers are synthesized for direct experimental investigation. This study provides important insights into decisive structural factors necessary to achieve robust and stable dielectrics with high energy storage capabilities at elevated temperature. We also find that the high-temperature insulation performance would experience diminishing marginal utility as the bandgap increases beyond a critical point, which is strongly correlated to the dihedral angle between neighboring planes of conjugation in these polymers. By experimentally testing the optimized and predicted structures, an increased energy storage at temperatures up to 250 °C is observed. We discuss the possibility for this strategy to be generally applied to other polymer dielectrics to achieve further performance enhancement.

Quantum Size Effect to Induce Colossal High-Temperature Energy Storage Density and Efficiency in Polymer/Inorganic Cluster Composites.

Polymer dielectrics need to operate at high temperatures to meet the demand of electrostatic energy storage in modern electronic and electrical systems. The polymer nanocomposite approach, an extensively proved strategy for performance improvement, encounters a bottleneck of reduced energy density and poor discharge efficiency beyond 150 °C. In this work, a polymer/metal oxide cluster composite prepared based on the "site isolation" strategy is reported. Capitalizing on the quantum size effect, the bandgap and surface defect states of the ultrasmall inorganic clusters (2.2 nm diameter) are modulated to markedly differ from regular-sized nanoparticles. Experimental results in conjunction with computational simulation demonstrate that the presence of ultrasmall inorganic clusters can introduce more abundant, deeper traps in the composite dielectric with respect to conventional polymer/nanoparticle blends. Unprecedented high-temperature capacitive performance, including colossal energy density (6.8 J cm-3 ), ultrahigh discharge efficiency (95%) and superior stability at different electric field frequencies, are achieved in these polymer/cluster composites up to 200 °C. Along with the advantages in material preparation (inexpensive precursors and one-pot synthesis), such polymer/inorganic cluster composite approach is promising for high-temperature dielectric energy storage in practical power apparatus and electronic devices.

Electroacupuncture regulates macrophage, neutrophil, and oral microbiota to alleviate alveolar bone loss and inflammation in experimental ligature-induced periodontitis.

AIM: Electroacupuncture (EA) regulates distant body physiology through somatic sensory autonomic reflexes, balances the microbiome, and can promote the release of immune cells into bloodstream, thereby inhibiting severe systemic inflammation. This makes it possible to use EA as an integrated treatment for periodontitis. MATERIALS AND METHODS: In this study, EA was applied to the ST36 acupoints in a ligature-induced periodontitis (LIP) mouse model. Then the effects of EA on periodontal myeloid cells, cytokines, and the microbiome were comprehensively analysed using flow cytometry, quantitative Polymerase Chain Reaction (PCR), and 16 S sequencing. RESULTS: Results demonstrated that EA could significantly relieve periodontal bone resorption. EA also suppressed the infiltration of macrophages and neutrophils, reduced gene expression of the pro-inflammatory cytokines IL-1ß, IL-6, IL-17 and TNF-α, and increased expression of the anti-inflammatory factors IL-4 and IL-10 in periodontal tissues. Moreover, composition of the periodontal microbiome was regulated by EA, finding that complex of microbiota, including supragingival Veillonella, subgingival Streptococcus, and subgingival Erysipelatoclostridium, were significantly reduced. Meanwhile, nitrate and nitrate-related activities of subgingival microbiota were reversed. Network analysis revealed close relationships among Veillonella, Streptococcus, and Bacteroides. CONCLUSIONS: Our study indicates that EA can effectively alleviate inflammation and bone resorption in LIP mice, potentially via the regulation of myeloid cells, cytokines, and periodontal microbiome.

Study on Performance Tests and the Application of Construction Waste as Subgrade Backfill.

The application of construction waste as an aggregate in subgrade backfilling is an important recycling option. This study analyzed a subgrade backfill material consisting of lime-fly ash construction waste mixture (LFCWM). Compaction and California bearing ratio (CBR) tests were performed on LFCWM under different cement-aggregate ratios (CARs, 3:7, 4:6, 5:5, 8:2). Different normal stresses (100, 200, and 300 kPa) and aggregate sizes (20%, 40%, 60%, 80% of P4.75) were also evaluated. The experimental results indicated that: (1) when the CAR was 4:6, the optimum water content and the maximum dry density reached their maximum values of 10.1% and 2.03 g/cm3, respectively, the maximum CBR value was 42.5%, and the shear strength reached its maximum value. (2) With an increase in shear displacement, the shear stress showed a rapid initial increase, then a slow decrease, and finally tended to stabilize. (3) Normal stress had a positive effect on the shear strength of the mixture. (4) When P4.75 was 40%, the shear strength of LFCWM was the maximum. The research results have been successfully applied to road engineering, providing an important reference for the application of construction waste aggregate in roadbed engineering.

Polymer/molecular semiconductor all-organic composites for high-temperature dielectric energy storage.

Dielectric polymers for electrostatic energy storage suffer from low energy density and poor efficiency at elevated temperatures, which constrains their use in the harsh-environment electronic devices, circuits, and systems. Although incorporating insulating, inorganic nanostructures into dielectric polymers promotes the temperature capability, scalable fabrication of high-quality nanocomposite films remains a formidable challenge. Here, we report an all-organic composite comprising dielectric polymers blended with high-electron-affinity molecular semiconductors that exhibits concurrent high energy density (3.0 J cm-3) and high discharge efficiency (90%) up to 200 °C, far outperforming the existing dielectric polymers and polymer nanocomposites. We demonstrate that molecular semiconductors immobilize free electrons via strong electrostatic attraction and impede electric charge injection and transport in dielectric polymers, which leads to the substantial performance improvements. The all-organic composites can be fabricated into large-area and high-quality films with uniform dielectric and capacitive performance, which is crucially important for their successful commercialization and practical application in high-temperature electronics and energy storage devices.

[Effect of low-intensity pulsed ultrasound combined with triamcinolone acetonide on oral mucosal ulcer healing in syrian hamster].

PURPOSE: To evaluate the effect of low-intensity pulsed ultrasound（LIPUS） combined with triamcinolone acetonide on oral mucosal ulcer in syrian hamster in several ways, including healing time, contents of superoxide dismutase（SOD）and malondialdehyde (MDA). METHODS: Sixty syrian hamsters were randomly divided into 5 groups, including a baseline group (containing a normal baseline group and a model baseline group, n=6) and 4 experimental groups (LIPUS processing and drug use group, LIPUS group, drug group and a normal control group without any processing, n=12). Four experimental groups and model baseline group were given oxygen free radicals to model the oral mucosal ulcer. At 24 h after the last treatment, the healing time of ulcer, content of SOD and MDA were compared between each group. SPSS 20.0 software package was used for statistical analysis. RESULTS: Compared with LIPUS group,drug group and control group, the healing time of oral mucosal ulcer in LIPUS and drug combined group was shortened. At 24 h after the last treatment, the activity of SOD showed that the LIPUS and drug combined group[(2.32±0.30) U/mgprot] were significantly higher than the model baseline group[(1.48±0.29) U/mgprot], the LIPUS group[(1.83±0.15) U/mgprot], the drug group[(1.76±0.25) U/mgprot] and control group[(1.71±0.18) U/mgprot] (P<0.05). The results of MDA content showed that the LIPUS and drug combined group [(8.17±0.21) nmol/mgprot] were significantly lower than the model baseline group[(9.41±0.22) nmol/mgprot], the LIPUS group[(9.00±0.44) nmol/mgprot], the drug group [(9.04±0.43) nmol/mgprot] and control group[(9.03±0.46) nmol/mgprot] (P<0.05). After oral mucosal ulcer healing, the activity of SOD and MDA showed that the LIPUS and drug combined group, the LIPUS group, the drug group and control group were not significantly different from the normal baseline group (P>0.05). CONCLUSIONS: Low-intensity pulsed ultrasound combined with triamcinolone acetonide can effectively improve the activity of SOD and reduce the contents of MDA in ulcerated tissues, and therefore accelerate the process of ulcer healing．.