Capsaicin attenuates Porphyromonas gingivalis-suppressed osteogenesis of periodontal ligament stem cells via regulating mitochondrial function and activating PI3K/AKT/mTOR pathway.

BACKGROUND AND OBJECTIVE: Prevention of periodontal bone resorption triggered by Porphyromonas gingivalis (P. gingivalis) is crucial for dental stability. Capsaicin, known as the pungent ingredient of chili peppers, can activate key signaling molecules involved in osteogenic process. However, the effect of capsaicin on osteogenesis of periodontal ligament stem cells (PDLSCs) under inflammation remains elusive. METHODS: P. gingivalis culture suspension was added to mimic the inflammatory status after capsaicin pretreatment. The effects of capsaicin on the osteogenesis of PDLSCs, as well as mitochondrial morphology, Ca2+ level, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and osteogenesis-regulated protein expression levels were analyzed. Furthermore, a mouse experimental periodontitis model was established to evaluate the effect of capsaicin on alveolar bone resorption and the expression of osteogenesis-related proteins. RESULTS: Under P. gingivalis stimulation, capsaicin increased osteogenesis of PDLSCs. Not surprisingly, capsaicin rescued the damage to mitochondrial morphology, decreased the concentration of intracellular Ca2+ and ROS, enhanced MMP and activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The in vivo results showed that capsaicin significantly attenuated alveolar bone loss and augmented the expression of bone associated proteins. CONCLUSION: Capsaicin increases osteogenesis of PDLSCs under inflammation and reduces alveolar bone resorption in mouse experimental periodontitis.

A Multifunctional Metal-Phenolic Nanocoating on Bone Implants for Enhanced Osseointegration via Early Immunomodulation.

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

Apoptotic Extracellular Vesicles Induced Endothelial Cell-Mediated Autologous Stem Cell Recruitment Dominates Allogeneic Stem Cell Therapeutic Mechanism for Bone Repair.

Although stem cell therapy is proved to be a promising strategy for bone repair and regeneration, transplanted allogeneic stem cells generally suffer from unfavorable apoptosis instead of differentiation into osteocytes. How the apoptotic stem cells promote bone regeneration still needs to be uncovered. In this work, we found that apoptotic extracellular vesicles released by allogeneic stem cells are critical mediators for promoting bone regeneration. Based on the results of in vivo experiments, a mechanism of apoptotic stem cells determined autologous stem cell recruitment and enhance osteogenesis was proposed. The nanoscaled apoptotic extracellular vesicles released from transplanted stem cells were endocytosed by vascular endothelial cells and preferentially distribute at endoplasmic reticular region. The oxidized phosphatidylcholine enriched in the vesicles activated the endoplasmic reticulum stress and triggered the reflective elevation of adhesion molecules, which induced the recruitment of autologous stem cells located in the blood vessels, transported them into the defect region, and promoted osteogenesis and bone repair. These findings not only reveal the mechanism of stem cell therapy of bone defects but also provide a cue for investigation of the biological process of stem cell therapy for other diseases and develop stem cell therapeutic strategies.

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study.

BACKGROUND: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. METHODS: Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher's exact test. ROC curve and surv_cutpoint function of 'survminer' package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. RESULTS: A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. CONCLUSIONS: Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

A Near-Infrared Photothermal-Responsive Underwater Adhesive with Tough Adhesion and Antibacterial Properties.

Developing tunable underwater adhesives that possess tough adhesion in service and easy detachment when required remains challenging. Herein, a strategy is proposed to design a near infrared (NIR) photothermal-responsive underwater adhesive by incorporating MXene (Ti3 C2 Tx )-based nanoparticles within isocyanate-modified polydimethylsiloxane (PDMS) polymer chains. The developed adhesive exhibits long-term and tough adhesion with an underwater adhesion strength reaching 5.478 MPa. Such strong adhesion is mainly attributed to the covalent bonds and hydrogen bonds at the adhesive-substrate interface. By making use of the photothermal-response of MXene-based nanoparticles and the thermal response of PDMS-based chains, the adhesive possesses photothermal-responsive performance, exhibiting sharply diminished adhesion under NIR irradiation. Such NIR-triggered tunable adhesion allows for easy and active detachment of the adhesive when needed. Moreover, the underwater adhesive exhibits photothermal antibacterial property, making it highly desirable for underwater applications. This work enhances the understanding of photothermal-responsive underwater adhesion, enabling the design of tunable underwater adhesives for biomedical and engineering applications.

Combined score based on plasma fibrinogen and platelet-lymphocyte ratio as a prognostic biomarker in esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score). METHODS: A total of 506 patients with ESCC were enrolled in this study. Harrell's concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis. RESULTS: Our result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p < 0.01). The result of Cox multivariable analysis showed that F-PLR score was an independent prognostic factor for OS (p = 0.002) and DFS (p = 0.003). In addition, F-PLR score presented the greater c-index values for OS and DFS compared with NLR, PLR and fibrinogen level. Our result also showed that the c-index values for OS and DFS were both greater in TNM + F-PLR than those in TNM stage alone. CONCLUSIONS: In conclusion, F-PLR score is a predictive biomarker for prognosis in patients with ESCC.

Phenolic Ligand-Metal Charge Transfer Induced Copper Nanozyme with Reactive Oxygen Species-Scavenging Ability for Chronic Wound Healing.

Chronic wounds frequently arise as a complication in diabetic patients, and their management remains a significant clinical hurdle due to their nonhealing nature featured by heightened oxidative stress and impaired healing cells at the wound site. Herein, we present a 2D copper antioxidant nanozyme induced by phenolic ligand-metal charge transfer (LMCT) to eliminate reactive oxygen species (ROS) and facilitate the healing of chronic diabetic wounds. We found that polyphenol ligands coordinated on the Cu3(PO4)2 nanosheets led to a strong charge transfer at the interface and regulated the valence states of Cu. The obtained Cu nanozyme exhibited efficient scavenging ability toward different oxidative species and protected human cells from oxidative damage. The nanozyme enhanced the healing of diabetic wounds by promoting re-epithelialization, collagen deposition, angiogenesis, and immunoregulation. This work demonstrates the LMCT-induced ROS scavenging ability on a nanointerface, providing an alternative strategy of constructing metal-based nanozymes for the treatment of diabetic wounds as well as other diseases.

Fusobacterium nucleatum dysregulates inflammatory cytokines and NLRP3 inflammasomes in oral cells.

OBJECTIVE: This study aimed to clarify the difference in Fusobacterium nucleatum (F. nucleatum) induced inflammatory cytokines and nod-like receptor protein 3 (NLRP3) inflammasomes dysregulation among three periodontal cells. METHODS: Oral epithelial cells (HIOECs), THP-1 macrophages, and human gingival fibroblasts (HGFs) were exposed to F. nucleatum with/without adenosine triphosphate (ATP) and nigericin (Nig). Cell morphology was assessed by scanning electron microscopy. qRT-PCR, protein microarrays, and bioinformatic methods were used to evaluate the cytokines and their complex interplay. NLRP3 inflammasomes activation was detected by western blotting and ELISA. RESULTS: F. nucleatum adhered to and invaded cells. In HIOECs, F. nucleatum enhanced interleukin (IL)-1α/1ß/6/10/13, TNF-α, and interferon (IFN)-γ expression. In THP-1 macrophages, F. nucleatum up-regulated IL-1α/1ß/6/10 and TNF-α levels. In HGFs, F. nucleatum increased IL-6 levels. F. nucleatum and ATP synergistically boosted IFN-γ level in THP-1 macrophages and IL-13 level in HGFs. IL-1α/1ß/6, and TNF-α served as epicenters of the inflammatory response. Additionally, F. nucleatum activated NLRP3 inflammasomes in HIOECs, and ATP/Nig boosted the activation. F. nucleatum also triggered NLRP3 inflammasomes in THP-1 macrophages, but in HGFs, only NLRP3 and caspase-1 levels were elevated. CONCLUSION: F. nucleatum infiltrated periodontal supporting cells and dysregulated inflammatory cytokines and NLRP3 inflammasomes.

Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment.

ABSTARCT: Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.

Using chitosan nanofibers to simultaneously improve the toughness and sensing performance of chitosan-based ionic conductive hydrogels.

Conductive hydrogels, especially polysaccharide-based ionic conductive hydrogels, have received increasing interest in the field of wearable sensors due to their similarity to human skin. Nevertheless, it is still a challenging task to simultaneously prepare a self-healed and adhesive conductive hydrogel with good toughness, temperature tolerance and high sensing performance, especially with high sensitivity and a low detection limit. Herein, we developed a new strategy to improve the toughness and sensing performance of a multifunctional conductive hydrogel by simultaneously using dissolved chitosan (CS) and solid chitosan nanofibers (CSFs) to induce the formation of hierarchical polymeric networks in the hydrogel. The tensile strength and elongation at break of the hydrogel could be improved from 70.3 kPa and 1005 % to 173.9 kPa and 1477 %, respectively, simply by introducing CSFs to the hydrogel, and its self-healing, adhesive and antibacterial properties were effectively retained. When serving as a resistive sensing material, the introduction of CSFs increased the gauge factor of the hydrogel-based strain sensor from 8.25 to 14.27. Moreover, the hydrogel-based strain sensor showed an ultralow detection limit of 0.2 %, excellent durability and stability (1000 cycles) and could be used to detect various human activities. In addition, the hydrogel prepared by using a water-glycerol binary solvent system showed temperature-tolerant performance and possessed adequate sensitivity when serving as a resistive sensing material. Therefore, this work provides a new way to prepare multifunctional conductive hydrogels with good toughness, sensing performance and temperature tolerance to expand the application range of hydrogel-based strain sensors.

Using chitosan nanofibers to synergistically construct a highly stretchable multi-functional liquid mental-based hydrogel for assembling strain sensor with high sensitivity and broad working range.

Liquid metal (LM) microdroplets have garnered significant interest as conductive materials for initiating free radical polymerization in the development of conductive hydrogels suited for strain sensors. However, crafting multi-functional conductive hydrogels that boast both high stretchability and superior sensing capabilities remains as a challenge. In this study, we have successfully synthesized LM-based conductive hydrogels characterized by remarkable stretchability and sensing performance employing acrylic acid (AA) to evenly distribute chitosan nanofibers (CSFs) and to subsequently catalyze the free radical polymerization of AA. The resultant polymer network was crosslinked within situ polyacrylic acid (PAA), facilitated by Ga3+ in conjunction with guar gum (GG)-stabilized Ga droplets. The strategic interplay between the rigid, and protonated CSFs and the pliable PAA matrix, coupled with the ionic crosslinking of Ga3+, endows the resulting GG-Ga-CSF-PAA hydrogel with high stretchability (3700 %), ultrafast self-healing, robust moldability, and strong adhesiveness. When deployed as a strain sensing material, this hydrogel exhibits a high gauge factor (38.8), a minimal detection threshold, enduring durability, and a broad operational range. This versatility enables the hydrogel-based strain sensor to monitor a wide spectrum of human motions. Remarkably, the hydrogel maintains its stretchability and sensing efficacy under extreme temperatures after a simple glycerol solution treatment.

The exoprotein Gbp of Fusobacterium nucleatum promotes THP-1 cell lipid deposition by binding to CypA and activating PI3K-AKT/MAPK/NF-κB pathways.

INTRODUCTION: Growing evidence has shown the correlation between periodontitis and atherosclerosis, while our knowledge on the pathogenesis of periodontitis-promoting atherosclerosis is far from sufficient. OBJECTIVES: Illuminate the pathogenic effects of Fusobacterium nucleatum (F. nucleatum) on intracellular lipid deposition in THP-1-derived macrophages and elucidate the underlying pathogenic mechanism of how F. nucleatum promoting atherosclerosis. METHODS AND RESULTS: F. nucleatum was frequently detected in different kinds of atherosclerotic plaques and its abundance was positively correlated with the proportion of macrophages. In vitro assays showed F. nucleatum could adhere to and invade THP-1 cells, and survive continuously in macrophages for 24 h. F. nucleatum stimulation alone could significantly promote cellular inflammation, lipid uptake and inhibit lipid outflow. The dynamic gene expression of THP-1 cells demonstrated that F. nucleatum could time-serially induce the over-expression of multiple inflammatory related genes and activate NF-κB, MAPK and PI3K-AKT signaling pathways. The exoprotein of F. nucleatum, D-galactose-binding protein (Gbp), acted as one of the main pathogenic proteins to interact with the Cyclophilin A (CypA) of THP-1 cells and induced the activation of the NF- κB, MAPK and PI3K-AKT signaling pathways. Furthermore, use of six candidate drugs targeting to the key proteins in NF- κB, MAPK and PI3K-AKT pathways could dramatically decrease F. nucleatum induced inflammation and lipid deposition in THP-1 cells. CONCLUSIONS: This study suggests that the periodontal pathogen F. nucleatum can activate macrophage PI3K-AKT/MAPK/NF-κB signal pathways, promotes inflammation, enhances cholesterol uptake, reduces lipid excretion, and promotes lipid deposition, which may be one of its main strategies promoting the development of atherosclerosis.

Hydro-Sensitive, In Situ Ultrafast Physical Self-Gelatinizing, and Red Blood Cells Strengthened Hemostatic Adhesive Powder with Antibiosis and Immunoregulation for Wound Repair.

Immediate and effective hemostatic treatments for complex bleeding wounds are an urgent clinical demand. Hemostatic materials with characteristics of adhesion, sealing, anti-infection, and concrescence promotion have drawn growing concerns. However, pure natural multifunctional hemostatic materials with in situ ultrafast self-gelation are rarely reported. In this study, a hydro-sensitive collagen/tannic acid (ColTA) natural hemostatic powder is developed that can in situ self-gel to form adhesive by the non-covalent crosslinking between tannic acid (TA) and collagen (Col) in liquids. The physical interactions endow ColTA adhesive with the characteristics of instantaneous formation and high adhesion at various substrate surfaces. Crucially, ColTA powder adhesive shows an enhanced adhesion performance in the presence of blood due to the electrostatic interactions between ColTA adhesive and red blood cells, conducive to effective in situ sealing and rapid hemostasis. The biocompatible and hemocompatible ColTA adhesive can effectively control bleeding and seal the wounds of the caudal vein, liver, heart, and femoral arteries in rats. Furthermore, the low-cost and ready-to-use ColTA adhesive powder also possesses good antibacterial and inhibiting biofilm formation ability, and can efficiently regulate immune response by the NF-κB pathway to promote wound repair, making it a highly promising hemostatic material with great potential for biomedical applications.

Microenvironment-Driven Fenton Nanoreactor Enabled by Metal-Phenolic Encapsulation of Calcium Peroxide for Effective Control of Dental Caries.

Caries are one of the most common oral diseases caused by pathogenic bacterial infections, which are widespread and persistently harmful to human health. Using nanoparticles to invade biofilms and produce reactive oxygen species (ROS) in situ is a promising strategy for killing bacteria and disrupting the structure of biofilms. In this work, a biofilm-targeting Fenton nanoreactor is reported that can generate ROS responsive to the cariogenic microenvironment. The nanoreactor is constructed by metal-phenolic encapsulation of calcium peroxide (CaO2) followed by modification with a biofilm targeting ligand dextran. Within the cariogenic biofilm, the Fenton nanoreactor is activated by an acidic microenvironment to be decomposed into H2O2 and iron ions, triggering a Fenton-like reaction to generate ROS that can eliminate the biofilm by breaking down extracellular polymeric substances (EPS) and killing cariogenic bacteria. Meanwhile, the depletion of excess protons in biofilm leads to a reversal of the cariogenic microenvironment. The Fenton nanoreactor can effectively inhibit the biofilm formation of Streptococcus mutans on ex vivo human teeth and is effective in preventing caries meanwhile maintaining the oral microbial diversity in rat caries infection model. This work provides a novel and efficient modality for acid microenvironment-driven ROS therapy.

[Retracted] Effects of miR­138­5p and miR­204­5p on the migration and proliferation of gastric cancer cells by targeting EGFR.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the numerous immunohistochemical images shown in Fig. 1D on p. 2626 exhibited a number of overlaps comparing among the data panels, such that data which were intended to show the results from differently performed experiments were likely to have been derived from a smaller number of original sources. A subsequent independent investigation of the data in this paper in the Editorial Office also revealed that certain of the cell migration and invasion assay data shown in Fig. 4A on p. 2629 were strikingly similar to data that had previously appeared in a couple of already published papers written by different authors at different research institutes.  Owing to the fact that the contentious data in Fig. 4 in the above article had already been published prior to its submission to Oncology Reports, in addition to the matter of several panels in Fig. 1D showing overlapping data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 2624-2634, 2018; DOI: 10.3892/or.2018.6389].

An underwater stable and durable gelatin composite hydrogel coating for biomedical applications.

Developing underwater stable and durable hydrogel coatings with drag-reducing, drug release, and antibacterial properties is essential for lots of biomedical applications. However, most hydrogel coatings cannot meet the requirement of underwater stability and versatility, which severely limits their widespread use. In this work, an underwater stable, durable and substrate-independent gelatin composite hydrogel (GMP) coating is developed through covalent crosslinks, where a silane coupling agent with an unsaturated double bond is grafted onto a substrate of co-deposited polydopamine and polyethylenimine. GMP coating can be easily coated onto various medical device surfaces, such as artificial joints, catheters, tracheal tubes and titanium alloys, showing excellent structural stability and mechanical tunability under extreme conditions of ultrasonic treatment for 1 h (400 W of ultrasonic power) or underwater shearing for 14 days (400 rpm). Besides, friction experiment reveals that GMP coating exhibits good lubrication properties (coefficient of friction < 0.003). The drug-loading and bacterial inhibition ring tests show that the GMP coating has a tunable drug release ability with the final releasing ratios of 70-95% by changing the content of poly (ethylene glycol) diacrylate. This work offers a scalable approach of fabricating bio-functional and stable hydrogel coatings, which can be potentially used in biomedical applications.

Adsorption characterization of tetracycline antibiotics on alkali-functionalized rice husk biochar and its evaluation on phytotoxicity to seed germination.

This work presented adsorption characteristics of tetracycline antibiotics (TCs) on KOH-functionalized rice husk biochar pyrolyzed at 700 °C (KBC700) and evaluation on phytotoxicity of TCs-adsorbed aqueous phase to seed germination. Specifically, KBC700 gained eightfold rise in specific surface area by KOH activation. Predominant monolayer chemisorption helped KBC700 control TCs, and spontaneous and exothermic features were identified by thermodynamic studies. KBC700 could efficiently work in a wide pH range (4.5 ~ 9.5), as well as in simulated eutrophic water and co-existing cationic solution. Humic acid exerted negative impact on TCs disposal. Outstanding regeneration capability and stability were also found during adsorption-desorption cycles. Mechanism discussion implied predominant pore filling and π-π interaction accompanied by hydrogen bonding and electrostatic interaction involved in TCs-removal process. Importantly, less phytotoxicity to seed germination was found in TCs-adsorbed aqueous phase. Collectively, these findings contribute to adsorption properties recognition and subsequent application for KOH-modified rice rusk biochar in environmental TCs remediation.

Mediating role of systemic inflammation in the association between heavy metals exposure and periodontitis risk.

BACKGROUND: This study evaluated the mediating role of systemic inflammation in the association between exposure to heavy metals and periodontitis in a nationwide sample of adults. METHODS: Pooled cross-sectional data from the National Health and Nutrition Examination Survey (NHANES 2009-2014) were used (n = 8993). Periodontitis was defined by a full-mouth examination and classified as no/mild and moderate/severe (mod/sev) groups. Blood and urinary heavy metal levels were investigated, including cadmium (Cd), lead (Pb), and mercury (Hg). In addition, systemic inflammation was assessed using circulatory leukocyte counts and C-reactive protein (CRP) levels. RESULTS: Multivariable logistic regression analysis revealed the positive associations of blood and urinary levels of Cd and Pb with mod/sev periodontitis. In contrast,blood Hg levels did not show a significant association. The odds of having periodontitis were 1.233 and 1.311 times higher for each one-unit increment in Ln-transformed blood Cd (95% confidence interval [CI]: 1.109-1.371) and Pb (95% CI: 1.170-1.470), respectively. Mediation analysis suggested a 6.3% to 11.5% contribution of leucocyte counts in the association of blood Cd and Pb levels with periodontitis. Sensitivity analyses for urinary Cd levels yielded consistent mediating effects. However, no significant mediating effect of CRP was detected. CONCLUSION: Higher exposures to Cd and Pb were positively associated with periodontitis risk. These associations might be partially mediated by the elevated levels of leukocytes rather than CRP. Further longitudinal studies are needed to elucidate the discordant results of the systemic inflammatory biomarkers.

Cartilage-Inspired Inhomogeneous Salt-Hydrogel for Hydrated Drag-Reducing and Strain Sensing.

Articular cartilages exhibit load-bearing capacity and durability due to their inhomogeneous structure. Inspired by this unique structure, a tough and inhomogeneous salt-hydrogel was developed by trapping sodium acetate (NaAc) crystals in polyacrylamide (PAM) polymer networks and then partially redissolving the NaAc crystals. The compressive and tensile stresses of the salt-hydrogel increase significantly by more than 20 times when oversaturated Ac- and Na+ are introduced into the gel network. Such an enhancement in mechanical strength is primarily attributed to the formation of NaAc crystals within the gel network. Further investigations reveal that the mechanical strength of the salt-hydrogel is temperature-dependent as the NaAc crystals gradually redissolve in the gel network with increasing temperature. Furthermore, redissolving NaAc crystals in an aqueous solution can yield an inhomogeneous salt-hydrogel. The topmost soft surface of the salt-hydrogel offers hydration lubrication, while the inhomogeneous network confers load-bearing capacity and durability. Compared to regular hydrogels, the inhomogeneous salt-hydrogel surface can realize drag reduction and remain smooth without damage after the friction tests. Moreover, a salt-hydrogel coating is also fabricated to visually demonstrate its drag-reducing property. In addition, this salt-hydrogel possesses conductivity and can be utilized in the development of inhomogeneous salt-hydrogel fibers (diameter = 438 ± 7 µm) for strain detection. The produced salt-hydrogel fiber exhibits excellent durability and reproducibility as a strain sensor, capable of detecting both small strains (e.g., 1%) and large strains (e.g., 40%). This work provides fundamental insights into developing hydrogels with an inhomogeneous network and explores their potential applications (e.g., hydrated drag-reducing, strain sensing).