Polygala tenuifolia willd. Extract alleviates LPS-induced acute lung injury in rats via TLR4/NF-κB pathway and NLRP3 inflammasome suppression.

BACKGROUND: Acute lung injury (ALI) has received considerable attention in the field of critical care as it can lead to high mortality rates. Polygala tenuifolia, a traditional Chinese medicine with strong expectorant properties, can be used to treat pneumonia. Owing to the complexity of its composition, the main active ingredient is not yet known. Thus, there is a need to identify its constituent compounds and mechanism of action in the treatment of ALI using advanced technological means. PURPOSE: We investigated the anti-inflammatory mechanism and constituent compounds with regard to the effect of P. tenuifolia Willd. extract (EPT) in lipopolysaccharide (LPS)-induced ALI in vivo and in vitro. METHODS: The UHPLC-Q-Exactive Orbitrap MS technology was used to investigate the chemical profile of EPT. Network pharmacology was used to predict the targets and pathways of action of EPT in ALI, and molecular docking was used to validate the binding of polygalacic acid to Toll-like receptor (TLR) 4. The main compounds were determined using LC-MS. A rat model of LPS-induced ALI was established, and THP-1 cells were stimulated with LPS and adenosine triphosphate (ATP) to construct an in vitro model. Pathological changes were observed using hematoxylin and eosin staining, Wright-Giemsa staining, and immunohistochemistry. The expression of inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) was determined using enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The LPS + ATP-induced inflammation model in THP-1 cells was used to verify the in vivo experimental results. RESULTS: Ninety-nine compounds were identified or tentatively deduced from EPT. Using network pharmacology, we found that TLR4/NF-κB may be a relevant pathway for the prevention and treatment of ALI by EPT. Polygalacic acid in EPT may be a potential active ingredient. EPT could alleviate LPS-induced histopathological lung damage and reduce the wet/dry lung weight ratio in the rat model of ALI. Moreover, EPT decreased the white blood cell and neutrophil counts in the bronchoalveolar lavage fluid and decreased the expression of genes and proteins of relevant inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) in lung tissues. It also increased the expression of endothelial-type nitric oxide synthase expression. Western blotting confirmed that EPT may affect TLR4/NF-κB and NLRP3 signaling pathways in vivo. Similar results were obtained in THP-1 cells. CONCLUSION: EPT reduced the release of inflammatory factors by affecting TLR4/NF-κB and NLRP3 signaling pathways, thereby attenuating the inflammatory response of ALI. Polygalacic acid is the likely compounds responsible for these effects.

Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics.

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.

Molecular mechanism of Danxiong Tongmai Granules in treatment of coronary heart disease.

BACKGROUND: Danxiong Tongmai Granules (DXTMG) are widely utilized in treating coronary heart disease (CHD) in China. This study aims to explore the molecular mechanisms underlying the therapeutic effects of DXTMG on CHD by employing a network pharmacology approach, complemented with experimental validation. METHODS: Traditional Chinese Medicine (TCM) compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database was used to obtain the main target genes involved in CHD. We combined disease targets with the drug targets to identify common targets. The "TCM-compound-target" network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock software. A molecular dynamics simulation was conducted on the optimal protein-small molecule complex identified through molecular docking, using Amber18 software. The rat model for myocardial ischemia was established through pre-gavage administration of DXTMG, followed by dorsal hypodermic injection of isoprenaline. Myocardial tissues from the rats were analyzed using hematoxylin and eosin (HE) staining and Masson's trichrome staining. Relevant targets were validated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system; 109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways (P < 0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. The results of molecular docking and molecular dynamics simulations demonstrated the robust binding affinity between the compounds and target proteins. Animal experiment findings indicated that, compared with the model group, the DXTMG group effectively ameliorated inflammation and fibrosis in rat myocardial tissues, reduced LDH, cTn-I, and MDA levels (P < 0.05, P < 0.01), elevated SOD and GSH-PX levels (P < 0.05), and reduced the percentage of positive area for IL-6 and TNF-α (P < 0.05). CONCLUSION: This study preliminarily suggests that DXTMG can modulate oxidative stress, inflammation response, and cardiomyocyte regulation, thereby mitigating the onset and progression of CHD.

Plantago consumption significantly reduces total cholesterol and low-density lipoprotein cholesterol in adults: A systematic review and meta-analysis.

Plantago is rich in soluble fiber, known for its beneficial health effects. Given this, we hypothesized that Plantago consumption might positively influence blood lipid in adults. Researchers have conducted numerous randomized controlled trials (RCTs), revealing the impacts of Plantago consumption on various blood lipid parameters. However, findings regarding specific blood lipid parameters have shown variability. This study aimed to comprehensively assess the effect of Plantago consumption on blood lipid parameters. Eligible studies evaluating the effects of Plantago consumption on blood lipid were searched in 5 electronic databases published up to August 2023. Analysis used a random effects model to determine weighted mean difference and 95% confidence intervals. In total, 29 RCTs including 2769 participants were included. Compared with the control group, Plantago consumption significantly reduced total cholesterol (TC) by 0.28 mmol/L and low-density lipoprotein cholesterol (LDL-C) by 0.35 mmol/L, correlating to an estimated 7% decrease in cardiovascular event risk. Conversely, no substantial effects were observed on high-density lipoprotein cholesterol or triglycerides. Subgroup analyses of 29 RCTs revealed that TC concentrations were significantly lowered in studies that included male participants, those who were healthy, or had lipid disorders. Additionally, TC and LDL-C were significantly lower in participants consuming Plantago husk or psyllium, and soluble fiber intake was specifically effective in lowering TC, LDL-C, and triglycerides. In conclusion, Plantago consumption can significantly lower TC and LDL-C concentrations. The findings will provide crucial insights into the potential of Plantago in dietary strategies for blood lipid management.

Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Dual-Color Real-Time Chemosensing of a Compartmentalized Reaction Network Involving Enzyme-Induced Membrane Permeation of Peptides.

The design of synthetic systems with interrelated reaction sequences that model incipient biological complexity is limited by physicochemical tools that allow the direct monitoring of the individual processes in real-time. To mimic a simple digestion-resorption sequence, the authors have designed compartmentalized liposomal systems that incorporate extra- and intravesicular chemosensing ensembles. The extravesicular reporter pair consists of cucurbit[7]uril and methylene blue to monitor the enzymatic cleavage of short enkephalin-related peptides by thermolysin through a switch-off fluorescence response ("digestion"). Because the substrate is membrane-impermeable, but the dipeptide product is permeable, uptake of the latter into the pre-formed liposomes occurs as a follow-up process. The intravesicular chemosensing ensemble consists of i) cucurbit[8]uril, 2-anilinonaphthalene-6-sulfonic acid, and methyl viologen or ii) cucurbit[7]uril and berberine to monitor the uptake ("resorption") of the enzymatic products through the liposomal membranes by i) a switch-on or ii) a switch-off fluorescence response. The dyes are designed to allow selective optical excitation and read-out of the extra- and intravesicular dyes, which allow for dual-color chemosensing and, therefore, kinetic discrimination of the two sequential reactions.

Salivary signatures of oral-brain communication in sleep bruxers.

Introduction: Microbiota and their interaction with hosts have been of great interest in brain research in recent years. However, the role of oral microbiota in mental illness and the underlying mechanism of oral-brain communication remains elusive. Sleep bruxism (SB) is an oral parafunctional activity related to the nervous system and is considered a risk factor for harmful clinical consequences and severe systemic conditions. Exploring the connection between oral microbiota and sleep bruxism may deepen our understanding of the complex relationship between oral-brain axis and provide insights for treatment. Methods: In this study, salivary samples were collected from 22 individuals with SB and 21 healthy controls, and metagenomics with metabolomics was performed. Nonparametric Wilcoxon test were applied for the statistical analysis between the two groups. Microbial dysbiosis and altered oral metabolites were found in the SB individuals. Results: The characteristic metabolite N-acetylglucosamine (GlcNAc) (VIP=8.4823, P<0.05) was correlated to a statistically lower Streptococcus mitis level in SB individuals. Salivary IFN-g level and IFN-g/IL-4 ratio were detected with significant changes in a chip assay. Amino acid metabolism pathways were upregulated, and the pathway with the largest number of differentially expressed genes is related to amino-tRNA charging pathway, while the most significantly enriched pathway is related to arginine biosynthesis. Neurotransmitter-associated pathways with glutamatergic and GABAergic synapses and cardiovascular system-related pathways were enriched in the SB group. Discussion: These results indicate a possible neuroimmune regulatory network of oral-brain communication in SB, which helps explain the mechanism of the oral microbiome with the host in sleep bruxers and provides a reference for early clinical and therapeutic intervention to improve the diagnosis and treatment of SB and similar diseases.

Effects of the pre-existing coronary heart disease on the prognosis of COVID-19 patients: A systematic review and meta-analysis.

Although studies have shown severe Coronavirus disease 2019 (COVID-19) outcomes in patients with pre-existing coronary heart disease (CHD), the prognosis of COVID-19 patients with pre-existing CHD remains uncertain primarily due to the limited number of patients in existing studies. This study aimed to investigate the impacts of pre-existing CHD on the prognosis of COVID-19 patients. Five electronic databases were searched for eligible studies. This article focused on cohort and case-control studies involving the prognosis of COVID-19 patients with pre-existing CHD. The meta-analysis was performed using a random effects model. The odds ratios (ORs) and 95% confidence intervals (CIs) were used as valid indicators. The study was registered in PROSPERO with the identifier: CRD42022352853. A total of 81 studies, involving 157,439 COVID-19 patients, were included. The results showed that COVID-19 patients with pre-existing CHD exhibited an elevated risk of mortality (OR = 2.45; 95%CI: [2.04, 2.94], P < 0.001), severe/critical COVID-19 (OR = 2.57; 95%CI: [1.98, 3.33], P < 0.001), Intensive Care Unit or Coronary Care Unit (ICU/CCU) admission: (OR = 2.75, 95%CI: [1.61, 4.72], P = 0.002), and reduced odds of discharge/recovery (OR = 0.43, 95%CI: [0.28, 0.66], P < 0.001) compared to COVID-19 patients without pre-existing CHD. Subgroup analyses indicated that the prognosis of COVID-19 patients with pre-existing CHD was influenced by publication year, follow-up duration, gender, and hypertension. In conclusion, pre-existing CHD significantly increases the risk of poor prognosis in patients with COVID-19, particularly in those male or hypertensive patients.

Liver-Inspired Polyetherketoneketone Scaffolds Simulate Regenerative Signals and Mobilize Anti-Inflammatory Reserves to Reprogram Macrophage Metabolism for Boosted Osteoporotic Osseointegration.

Tissue regeneration is regulated by morphological clues of implants in bone defect repair. Engineered morphology can boost regenerative biocascades that conquer challenges such as material bioinertness and pathological microenvironments. Herein, a correlation between the liver extracellular skeleton morphology and the regenerative signaling, namely hepatocyte growth factor receptor (MET), is found to explain the mystery of rapid liver regeneration. Inspired by this unique structure, a biomimetic morphology is prepared on polyetherketoneketone (PEKK) via femtosecond laser etching and sulfonation. The morphology reproduces MET signaling in macrophages, causing positive immunoregulation and optimized osteogenesis. Moreover, the morphological clue activates an anti-inflammatory reserve (arginase-2) to translocate retrogradely from mitochondria to the cytoplasm due to the difference in spatial binding of heat shock protein 70. This translocation enhances oxidative respiration and complex II activity, reprogramming the metabolism of energy and arginine. The importance of MET signaling and arginase-2 in the anti-inflammatory repair of biomimetic scaffolds is also verified via chemical inhibition and gene knockout. Altogether, this study not only provides a novel biomimetic scaffold for osteoporotic bone defect repair that can simulate regenerative signals, but also reveals the significance and feasibility of strategies to mobilize anti-inflammatory reserves in bone regeneration.

Wnt3a-Loaded Hydroxyapatite Nanowire@Mesoporous Silica Core-Shell Nanocomposite Promotes the Regeneration of Dentin-Pulp Complex via Angiogenesis, Oxidative Stress Resistance, and Odontogenic Induction of Stem Cells.

Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a-loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a-HANW@MpSi) core-shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a-HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a-HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin-pulp complex-like tissues and blood vessels by Wnt3a-HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a-HANW@MpSi in treatments of dental pulp exposure.

Shiwei Qingwen decoction regulates TLR4/NF-κB signaling pathway and NLRP3 inflammasome to reduce inflammatory response in lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shiwei Qingwen decoction (SWQ), a Chinese herbal formula based on the classic traditional Chinese medicine prescription Yu Ping Feng San, has shown efficacy in preventing and treating early pneumonia with good clinical outcomes. However, its underlying mechanism is yet unclear. AIM OF THE STUDY: To clarify the preventive and therapeutic effects of SWQ on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the underlying mechanism by which SWQ influences pneumonia. MATERIALS AND METHODS: First, the chemical composition of SWQ was preliminarily determined by high performance liquid chromatography (HPLC), and the impact of SWQ (3.27, 6.55, and 13.1 g/kg) was assessed in the LPS-induced ALI rat model. Next, its inflammatory pathway was determined via network pharmacology. Finally, the molecular mechanism of SWQ was validated using a rat ALI model and a THP-1 cell inflammation model. RESULTS: HPLC identified chlorogenic acid, prime-O-glucosylcimifugin, calycosin, and 5-O-methylaminoside in the chemical profile of SWQ. In the ALI model, SWQ alleviated ALI by reducing lung wet/dry weight ratio (W/D) and preventing histopathological damage to the lungs. At the same time, SWQ decreased penetration of inflammatory mediators by upregulating AQP1 and AQP5 and endothelial nitric oxide synthase (eNOS). Pretreatment with SWQ downregulated white blood cells and neutrophils count in BALF and suppressed LPS-induced expression levels of MPO, NE, and pro-inflammatory factors (TNF-α, IL-1ß, IL-6, and iNOS). Network pharmacology showed that SWQ was associated with TLR4/NF-κB inflammation pathway. Moreover, pretreatment with SWQ reduced the expression level of TLR4/NF-κB signaling pathway-associated proteins (TLR4, Myd88, p-IκB, and p-p65) and NLRP3 inflammasome (NLRP3, ASC, caspase-1, and cleaved-IL-1ß) in vivo and vitro. CONCLUSIONS: The present study demonstrates that SWQ can reduce inflammation in ALI by inhibiting TLR4/NF-κB and NLRP3 inflammasome activation.

Transcriptome landscape comparison of periodontium in developmental and renewal stages.

Objectives: Periodontium regeneration remains a significant challenge in clinics and research, and it is essential to understand the stage-specific biological process in situ. However, differing findings have been reported, and the mechanism has yet to be elucidated. The periodontium of adult mice molars is considered to be stable remodeling tissue. At the same time, the continuously growing incisors and the developing dental follicle (DF) of postnatal mice highly represent fast remodeling tissue. In this study, we attempted to explore different clues of temporal and spatial comparisons to provide improved references for periodontal regeneration. Methods: Periodontal tissues from the developing periodontium (DeP) of postnatal mice, and continuously growing periodontium (CgP) and stable remodeling periodontium (ReP) of adult mice were isolated and compared using RNA sequencing. Based on the Dep and CgP separately compared with the ReP, differentially expressed genes and signaling pathways were analyzed using GO, KEGG databases, and Ingenuity Pathway Analysis (IPA). The results and validation were obtained by immunofluorescence staining and RT-PCR assays. Data were expressed as means ± standard deviation (SD) and analyzed by GraphPad Prism 8 software package, and one-way ANOVA was used to test multiple groups. Results: Principal component analysis showed that the three groups of periodontal tissue were successfully isolated and had distinct expression profiles. A total of 792 and 612 DEGs were identified in the DeP and CgP groups compared with the ReP. Upregulated DEGs in the DeP were closely related to developmental processes, while the CgP showed significantly enhanced cellular energy metabolism. The DeP and CgP showed a common downregulation of the immune response, with activation, migration, and recruitment of immune cells. IPA and further validation jointly suggested that the MyD88/p38 MAPK pathway played an essential regulatory role in periodontium remodeling. Conclusion: Tissue development, energy metabolism, and immune response were critical regulatory processes during periodontal remodeling. Developmental and adult stages of periodontal remodeling showed different expression patterns. These results contribute to a deeper understanding of periodontal development and remodeling and may provide references for periodontal regeneration.

Different responses of Chlorella vulgaris to silver nanoparticles and silver ions under modulation of nitric oxide.

Silver nanoparticles (Ag-NPs) are widely used in daily life because of their antibacterial properties. A fraction of Ag-NPs are released into the ecosystem during their production and utilization. The toxicity of Ag-NPs has been reported. However, it is still disputed whether the toxicity is mainly due to the released silver ions (Ag+). In addition, few studies have reported the response of algae to metal nanoparticles under modulation of nitric oxide (NO). In this study, Chlorella vulgaris (C. vulgaris) was used as a model organism to study the toxic effects of Ag-NPs and Ag+ released from Ag-NPs on algae under the modulation of NO. The results showed that the biomass inhibition rate of Ag-NPs (44.84%) to C. vulgaris was higher than that of Ag+ (7.84%). Compared with Ag+, Ag-NPs induced more severe damage to photosynthetic pigments, photosynthetic system II (PSII) performance, and lipid peroxidation. More serious damage to cell permeability led to higher internalization of Ag under Ag-NPs stress. Application of exogenous NO reduced the inhibition ratio of photosynthetic pigments and chlorophyll autofluorescence. Further, NO reduced the MDA levels by scavenging reactive oxygen species induced by Ag-NPs. NO modulated the secretion of extracellular polymers and hampered the internalization of Ag. All these results showed that NO alleviates the toxicity of Ag-NPs to C. vulgaris. However, NO did not improve the toxic effects of Ag+. Our results provide new insights into the toxicity mechanism of Ag-NPs to algae modulated by the signal molecule NO.

A novel continuous all-weather photo-electric synergistic treatment system for refractory organic compounds and its application in degrading enrofloxacin.

A novel continuous all-weather photo-electric synergistic treatment system was proposed in this study for refractory organic compounds, which overcame the defects of conventional photo-catalytic treatments that rely on light irradiation and thus cannot achieve all-weather continuous treatment. The system used a new photocatalyst (MoS2/WO3/carbon felt) with the characteristics of easy recovery and fast charge transfer. The system was systematically tested in degrading enrofloxacin (EFA) under real environmental conditions in terms of treatment performance, pathways and mechanisms. The results showed that the EFA removal of photo-electric synergy substantially increased by 1.28 and 6.78 times, compared to photocatalysis and electrooxidation, respectively, with an average removal of 50.9% under the treatment load of 832.48 mg m-2 d-1. Possible treatment pathways of EFA and mechanism of the system were found to be mainly the loss of piperazine groups, the cleavage of the quinolone portion and the promotion of electron transfer by bias voltage.

Strontium-incorporated bioceramic scaffolds for enhanced osteoporosis bone regeneration.

The restoration of bone defects caused by osteoporosis remains a challenge for surgeons. Strontium ranelate has been applied in preventative treatment approaches due to the biological functions of the trace element strontium (Sr). In this study, we aimed to fabricate bioactive scaffolds through Sr incorporation based on our previously developed modified amino-functional mesoporous bioactive glass (MBG) and to systematically investigate the bioactivity of the resulting scaffold in vitro and in vivo in an osteoporotic rat model. The results suggested that Sr-incorporated amino-functional MBG scaffolds possessed favorable biocompatibility. Moreover, with the incorporation of Sr, osteogenic and angiogenic capacities were upregulated in vitro. The in vivo results showed that the Sr-incorporated amino-functional MBG scaffolds achieved better bone regeneration and vessel formation. Furthermore, bioinformatics analysis indicated that the Sr-incorporated amino-functional MBG scaffolds could reduce reactive oxygen species levels in bone marrow mesenchymal stem cells in the osteoporotic model by activating the cAMP/PKA signaling pathway, thus playing an anti-osteoporosis role while promoting osteogenesis. This study demonstrated the feasibility of incorporating trace elements into scaffolds and provided new insights into biomaterial design for facilitating bone regeneration in the treatment of osteoporosis.

Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.

Trace Element-Augmented Titanium Implant With Targeted Angiogenesis and Enhanced Osseointegration in Osteoporotic Rats.

Deteriorated bone quality in osteoporosis challenges the success of implants, which are in urgent need for better early osseointegration as well as antibacterial property for long-term stability. As osteoporotic bone formation tangles with angiogenic clues, the relationship between osteogenesis and angiogenesis has been a novel therapy target for osteoporosis. However, few designs of implant coatings take the compromised osteoporotic angiogenic microenvironment into consideration. Here, we investigated the angiogenic effects of bioactive strontium ions of different doses in HUVECs only and in a co-culture system with BMSCs. A proper dose of strontium ions (0.2-1 mM) could enhance the secretion of VEGFA and Ang-1 in HUVECs as well as in the co-culture system with BMSCs, exhibiting potential to create an angiogenic microenvironment in the early stage that would be beneficial to osteogenesis. Based on the dose screening, we fabricated a bioactive titanium surface doped with zinc and different doses of strontium by plasma electrolytic oxidation (PEO), for the establishment of a microenvironment favoring osseointegration for osteoporosis. The dual bioactive elements augmented titanium surfaces induced robust osteogenic differentiation, and enhanced antimicrobial properties. Augmented titanium implant surfaces exhibited improved bone formation and bone-implant contact under comprehensive assessment of an in vivo bone-implant interface. In conclusion, zinc- and strontium-augmented titanium surface benefits the osseointegration in osteoporosis via promoting osteogenic differentiation, exerting antibacterial efficacy, and stimulating early angiogenesis.

Numerical modeling of changes in groundwater storage and nitrate load in the unconfined aquifer near a river receiving reclaimed water.

Reclaimed water (RW) has been widely used as an alternative water resource to recharge rivers in mega-city Beijing. At the same time, the RW also recharges the ambient aquifers through riverbank filtration and modifies the subsurface hydrodynamic system and hydrochemical characteristics. To assess the impact of RW recharge on the unconfined groundwater system, we conducted a 3D groundwater flow and solute transport model based on 10 years of sequenced groundwater monitoring data to analyze the changes of the groundwater table, Cl- loads, and NO3-N loads in the shallow aquifer after RW recharge to the river channel. The results show that the groundwater table around the river channel elevated by about 3-4 m quickly after RW recharge from Dec. 2007 to Dec. 2009, and then remained stable due to the continuous RW infiltration. However, the unconfined groundwater storage still declined overall from 2007 to 2014 due to groundwater exploitation. The storage began to recover after groundwater extraction reduction, rising from 3.76 × 108 m3 at the end of 2014 to 3.85 × 108 m3 at the end of 2017. Cl- concentrations varied from 5-75 mg/L before RW recharge to 50-130 mg/L in 2 years (2007-2009), and then remained stable. The zones of the unconfined groundwater quality affected by RW infiltration increased from 11.7 km2 in 2008 to 26.7 km2 in 2017. Cl- loads in the zone increased from 1.8 × 103 t in 2008 to 3.8 × 103 t in 2017, while NO3-N loads decreased from 29.8 t in 2008 to 11.9 t in 2017 annually. We determined the maximum area of the unconfined groundwater quality affected by RW, and groundwater outside this area not affected by RW recharge keeps its original state. The RW recharge to the river channel in the study area is beneficial to increase the groundwater table and unconfined groundwater storage with lesser environmental impacts.

Effect of Chlamydomonas reinhardtii on the fate of CuO nanoparticles in aquatic environment.

In this study, the effect of Chlamydomonas reinhardtii on the fate of CuO nanoparticles (CuO-NPs) in aquatic environment were investigated in terms of the colloidal stability, the free Cu2+ releasing, extracellular adsorption Cu (Cuex) and intracellular assimilation Cu (Cuin). The results showed that, with the increasing microalgal density, the absolute value of zeta potential of CuO-NPs decreased and the mean hydrodynamic diameter (MHD) became larger, leading to a better aggregation and settling behavior of CuO-NPs. The microalgae also promoted the free Cu2+ releasing, however, inhibited adsorption and assimilation of metal nanoparticles (MNPs) into microalgal cells, resulting in the reduction of the Cuex and Cuin per microalgal cell. The phenomenon was probably due to the reduced chance of contact between microalgae and MNPs. The internalization of CuO-NPs was also observed in microalgal cells by high resolution transmission electron microscope (HRTEM). Furthermore, the results of fast fourier transform (FFT)/inversed FFT (IFFT) analysis indicated that the CuO-NPs was reduced to Cu2O-NPs in the microalgae cells. The above results suggested that the microalgae can significantly affect the fate of MNPs, and subsequently, influencing the bioavailability and toxicity of MNPs in the aquatic environment.

Product-oriented decomposition of lignocellulose catalyzed by novel polyoxometalates-ionic liquid mixture.

Lignocellulose was oxidatively decomposed in a newly developed polyoxometalates-imidazolium ionic liquid mixture. Aromatic compounds covering acids, esters, ketones, aldehydes, and phenols were selectively produced under various conditions. 4-Hydroxylbenzoic acid was dominatingly yielded under low temperature and high oxidant concentration. Phenolic compounds were mainly generated at high temperature with a selectivity of 45.1% and a yield of 4.3%, higher than those generated in similar polyoxometalates-ionic liquids system. The products distributions and residues of lignocellulose decomposition under various conditions were characterized; the influences of the ionic liquids anions on the polyoxometalates-ionic liquids complex formation, the acidic and redox properties of the catalyst, and the final products were profoundly investigated; and a tentative reacting process was proposed. The ionic liquid could be recycled for five times. This work not only provided a new lignocellulose decomposition strategy to produce aromatic products, but also offered a guidance for product-oriented lignocellulose decomposition.