Regulation of RIP1-Mediated necroptosis via necrostatin-1 in periodontitis.

OBJECTIVE: To explore the mechanism of receptor-interacting protein 1 (RIP1)-mediated necroptosis during periodontitis progression. BACKGROUND: RIP3 and mixed lineage kinase domain-like protein (MLKL) have been detected to be upregulated in periodontitis models. Because RIP1 is involved in necroptosis, it might also play a role in the progression of periodontitis. METHODS: An experimental periodontitis model in BALB/c mice was established by inducing oral bacterial infection. Western blotting and immunofluorescence analyses were used to detect RIP1 expression in the periodontal ligament. Porphyromonas gingivalis was used to stimulate L929 and MC3T3-E1. RIP1 was inhibited using small-interfering RNA. Western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the effect of necroptosis inhibition on the expression of damage-associated molecular patterns and inflammatory cytokines. Necrostatin-1 (Nec-1) was intraperitoneally injected to inhibit RIP1 expression in mice. Necroptosis activation and inflammatory cytokine expression in periodontal tissue were verified. Tartrate-resistant acid phosphatase staining was applied to observe osteoclasts in the bone tissues of different groups. RESULTS: RIP1-mediated necroptosis was activated in mice with periodontitis. P. gingivalis induced RIP1-mediated necroptosis in L929 and MC3T3-E1 cells. After RIP1 inhibition, the expression levels of high mobility group protein B1 (HMGB1) and inflammatory cytokines were downregulated. After inhibiting RIP1 with Nec-1 in vivo, necroptosis was also inhibited, the expression levels of HMGB1 and inflammatory cytokines were downregulated, and osteoclast counts in the periodontal tissue decreased. CONCLUSION: RIP1-mediated necroptosis plays a role in the pathological process of periodontitis in mice. Nec-1 inhibited necroptosis, alleviated inflammation in periodontal tissue, and reduced bone resorption in periodontitis.

Activation of receptor-interacting protein 3-mediated necroptosis accelerates periodontitis in mice.

OBJECTIVE: To investigate the involvement and role of receptor-interacting protein 3 (RIP3)-mediated necroptosis in periodontitis. METHODS: A periodontitis murine model was established by oral infection with Porphyromonas gingivalis, and activation of necroptosis pathway was identified by immunohistochemistry. Adeno-associated virus was used to knock down Rip3 and the effect of Rip3 knockdown on periodontal inflammation was examined by Micro-CT, qRT-PCR and histological staining. In vitro, P. gingivalis-LPS was used to infect fibroblast cell line L929 and siRNA was used to knock down Rip3. Necroptosis pathway signalling and inflammation in cells were detected by cell viability and death assay, Western Blot, qRT-PCR and immunofluorescence analysis. RESULTS: Phosphorylation of RIP3 and mixed lineage kinase domain-like protein (MLKL) was increased in the periodontal ligament of mice infected with P. gingivalis. RIP3 knockdown reduced osteoclastogenesis and inflammatory cytokines in the periodontal area, and alleviated alveolar bone loss in vivo. In vitro, P. gingivalis-LPS-induced RIP3-mediated necroptosis in L929 cells, and knockdown of RIP3 by siRNA decreased the expression of inflammatory cytokines. CONCLUSION: RIP3-mediated necroptosis is activated in periodontitis and blocking necroptosis alleviates disease progression, indicating that RIP3 may be a potential target for periodontitis treatment.

Inhibition of Rgs10 aggravates periodontitis with collagen-induced arthritis via the nuclear factor-κB pathway.

OBJECTIVE: To explore the role of the Rgs10-associated nuclear factor (NF)-κB signalling pathway in periodontitis with rheumatoid arthritis. METHODS: Porphyromonas gingivalis and collagen were locally applied to mice to establish in vivo periodontitis and rheumatoid arthritis models, respectively. Both agents were administered together to establish the comorbid group. All models were treated with adeno-associated virus-green fluorescent protein (AAV-GFP) or adeno-associated virus small hairpin Rgs10 (AAV-sh-Rgs10). In vivo expression of Rgs10 and inflammatory cytokines was analysed, along with exploration of the NF-κB signalling pathway in lipopolysaccharide-stimulated mouse-derived RAW264.7 cells, with and without treatment of small interfering RNA (siRNA; Rgs10-Mus-MSS245072). RESULTS: In the comorbidity mouse group (mice with both periodontitis and rheumatoid arthritis), inhibition of Rgs10 exacerbated periodontitis, along with upregulation of phospho-RelA (pP65), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression in the NF-κB signalling pathway. Similarly, treatment of LPS-stimulated RAW264.7 cells with siRNA resulted in the inhibition of Rgs10, along with upregulation of pP65, TNF-α and IL-6 expression in vitro. CONCLUSION: Inhibition of Rgs10 in mice with periodontitis and rheumatoid arthritis can promote the progression of periodontitis, indicating the potential therapeutic role of Rgs10 in this condition.

Inhibition of receptor-interacting protein kinase-3 in the necroptosis pathway attenuates inflammatory bone loss in experimental apical periodontitis in Balb/c mice.

AIM: To explore the role of necroptosis in apical periodontitis (AP), this study investigated necroptosis in a Fusobacterium nucleatum (Fn)-induced AP model of Balb/c mice and explored related intracellular signalling pathways in L929 cells affected by Fn. METHODOLOGY: For the in vivo experiments, expression of receptor-interacting protein kinase-3 (RIP3) was inhibited using an adeno-associated virus and then the Balb/c mice model of AP was established by injecting Fn into the root canal of the first mandibular molars. Bone loss and number of osteoclasts were measured via micro-computed tomography and tartrate-resistant acid phosphatase staining, respectively; expression of RIP3 and phosphorylated mixed lineage kinase domain-like protein (pMLKL) was detected by immunohistochemistry and western blotting; expression of mRNA of inflammatory cytokines was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). For the in vitro experiments, L929 cells transfected with RIP3-Mus-siRNA or negative control siRNA were co-cultured with Fn; thereafter, western blotting, detection of cell death and viability and qRT-PCR analyses were performed to assess the activation of necroptosis pathway and expression of mRNA of inflammatory cytokines. Data were analysed with unpaired t-test and one-way analysis of variance with significance set at p < .05. RESULTS: The Fn-induced apical lesions were associated with apical bone loss, an increased number of osteoclasts, enhanced expression of pMLKL and increased mRNA levels of inflammatory cytokines(IL-1α and IL-1ß); all these effects were alleviated by RIP3 inhibition (p < .05). L929 cells infected with Fn displayed increased expression of pMLKL and increased cell death (p < .05), together with decreased cell viability (p < .05), whilst transfection with RIP3-Mus-siRNA decreased the mRNA expression of inflammatory cytokines(TNF-α and IL-6, p < .05). CONCLUSIONS: Necroptosis may be involved in AP progression. RIP3 inhibition ameliorated the expression of inflammatory cytokines and bone resorption in Fn-induced AP lesions in Balb/c mice.

Inhibition of Cathepsin K Alleviates Autophagy-Related Inflammation in Periodontitis-Aggravating Arthritis.

Rheumatoid arthritis (RA) and periodontitis share many epidemiological and pathological features, with emerging studies reporting a relationship between the two diseases. Recently, RA and periodontitis have been associated with autophagy. In the present study, we investigated the effects of cathepsin K (CtsK) inhibition on RA with periodontitis in a mouse model and its immunological function affecting autophagy. To topically inhibit CtsK periodontitis with arthritis in the animal model, adeno-associated virus (AAV) transfection was performed in periodontal and knee joint regions. Transfection of small interfering RNA (siRNA) was performed to inhibit CtsK in RAW264.7 cells. The effects of CtsK inhibition on the autophagy pathway were then evaluated in both in vivo and in vitro experiments. RA and periodontitis aggravated destruction and inflammation in their respective lesion areas. Inhibition of CtsK had multiple effects: (i) reduced destruction of alveolar bone and articular tissue, (ii) decreased macrophage numbers and inflammatory cytokine expression in the synovium, and (iii) alleviated expression of the autophagy-related transcription factor EB (TFEB) and microtubule-associated protein 1A/1B-light chain 3 (LC3) at the protein level in knee joints. Inhibition of CtsK in vitro reduced the expression of autophagy-related proteins and related inflammatory factors. Our data revealed that the inhibition of CtsK resisted the destruction of articular tissues and relieved inflammation from RA with periodontitis. Furthermore, CtsK was implicated as an imperative regulator of the autophagy pathway in RA and macrophages.

One-Step Monitoring of Multiple Enterovirus 71 Infection-Related MicroRNAs Using Core-Satellite Structure of Magnetic Nanobeads and Multicolor Quantum Dots.

The accurate and rapid monitoring of the expression levels of enterovirus 71 (EV71)-related microRNAs (miRNAs) can contribute to diagnosis of hand, foot, and mouth disease (HFMD) at the early stage. However, there is currently a lack of convenient methods for simultaneous monitoring of multiplex miRNAs in one step. Herein a one-step method for the simultaneous monitoring of multiple EV71 infection-related miRNAs is developed based on core-satellite structure assembled with magnetic nanobeads and quantum dots (MNs-ssDNA-QDs). In the presence of target miRNAs, duplex-specific nuclease (DSN)-assisted target recycling can be triggered, resulting in the release of QDs and recycling of target miRNAs. Then the simultaneous quantification can be easily realized by recording the corresponding amplified fluorescence signal of QDs in the suspension. With this method, simultaneous detection of hsa-miRNA-296-5p and hsa-miRNA-16-5p, potential biomarkers of EV71 infection, can be easily achieved with femtomolar sensitivity and single-base mismatch specificity. Moreover, the method is successfully used for monitoring of the expression level of miRNAs in EV71-infected cells at different time points, demonstrating the potential for diagnostic applications. With the merits of one-step operation and single-nucleotide mismatch discrimination, this work opens a new avenue for multiplex miRNAs detection. As different nucleotide sequences and multicolor QDs can be employed, this work is expected to offer great potential for the development of high throughput diagnosis.

A critical review on the sources and instruments of marine microplastics and prospects on the relevant management in China.

The world's oceans are suffering a constant and unprecedented accumulation of emerging plastic contaminants known as microplastics with a particle diameter smaller than 5mm. Microplastics exhibit a widespread distribution in various habitats from land to the oceans, and even reach the most remote regions - the deep sea and the polar, receiving attention exponentially in the past few years. Owing to their small size, marine species risk getting ingested and entangled in microplastics, causing suffocation, starvation, physical trauma or damage from chemicals, which poses vast and growing threats to biodiversity and the food web. This review article focuses on the various sources attributed to marine microplastics, the latest international, regional and national countermeasures to combat marine litter, as well as the status quo of microplastics pollution, legislation and regulations in China, and furthermore provides improving proposals/solutions on key research gaps, governance and management for future environmental control and policymaking in China.

Simultaneous Point-of-Care Detection of Enterovirus 71 and Coxsackievirus B3.

Human enterovirus 71 (EV71) is one of the pathogens that causes hand, foot, and mouth disease (HFMD), which generally leads to neurological diseases and fatal complications among children. Since the early clinical symptoms from EV71 infection are very similar to those from Coxsackievirus B3 (CVB3) infection, a robust and sensitive detection method that can be used to distinguish EV71 and CVB3 is urgently needed for prompting medical treatment of related diseases. Herein, based on immunomagnetic nanobeads and fluorescent semiconductor CdSe quantum dots (QDs), a method for simultaneous point-of-care detection of EV71 and CVB3 is proposed. The synchronous detection of EV71 and CVB3 virions was achieved within 45 min with high specificity and repeatability. The limits of detection are 858 copies/500 µL for EV71 and 809 copies/500 µL for CVB3.This proposed method was further validated with 20 human throat swab samples obtained from EV71 or CVB3 positive cases, with results 93.3% consistent with those by the real-time PCR method, demonstrating the potential of this method for clinical quantification of EV71 and CVB3. The method may also facilitate the prevention and treatment of the diseases.

Functional outcome of en bloc excision and custom prosthetic replacement for giant cell tumor of the distal radius.

BACKGROUND: Giant cell tumors (GCT) of the distal radius at Campanacci grade II/III are particularly challenging to treat. Wide excision is the management of choice, but this creates a defect at the distal end of radius. We treated 11 cases of GCT of the distal radius by en bloc excision and custom prosthetic replacement. The purpose of this study was to present our experience and assess the functional outcomes of all patients treated with this surgery. MATERIALS AND METHODS: Between 2005 and 2014, we followed up 11 patients with GCT of the distal radius who were treated with en bloc excision and custom prosthetic replacement. All cases were evaluated based on clinical and radiological examinations, passive range of motion (ROM) of the wrist joint, complications, and Musculoskeletal Tumor Society (MSTS) score. RESULTS: Mean follow-up period was 55.5 months (24-83 months); mean resected length of the radius was 7.9 cm. One patient had tumor recurrence in the soft tissues after 15 months (recurrence rate 9.09 %). No patient had fracture, recurrence in the bone, metastases, or immune rejection. No complications were seen, such as loosening, rupture, or dislocation of the custom prosthesis. One patient developed superficial infection at the operative site which resolved after a course of antibiotics for 4 weeks. One patient experienced pain, which could be endured without the need for analgesics. Average ROM was 40.9° of dorsiflexion, 30.0° of volar flexion, 46.4° of supination, and 38.2° of pronation. Mean grip strength was 71 % (42-86 %). Overall revised MSTS score averaged 80.3 % (63.3-93.3 %) with one being excellent, five good, and five satisfactory. CONCLUSION: En bloc excision and custom prosthetic replacement for a Campanacci grade II/III GCT of the distal radius results in reasonable functional outcome at intermediate follow-up evaluation. Although average ROM of the ipsilateral wrist is poorer than some studies with other techniques, this method can be considered a reasonable option.

The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients' orthodontic treatment.

In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice.

Despite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.

A Biodegradable Fiber Calcium Ion Sensor by Covalently Bonding Ionophores on Bioinert Nanoparticles.

Implantable sensors, especially ion sensors, facilitate the progress of scientific research and personalized healthcare. However, the permanent retention of implants induces health risks after sensors fulfill their mission of chronic sensing. Biodegradation is highly anticipated; while; biodegradable chemical sensors are rare due to concerns about the leakage of harmful active molecules after degradation, such as ionophores. Here, a novel biodegradable fiber calcium ion sensor is introduced, wherein ionophores are covalently bonded with bioinert nanoparticles to replace the classical ion-selective membrane. The fiber sensor demonstrates comparable sensing performance to classical ion sensors and good flexibility. It can monitor the fluctuations of Ca2+ in a 4-day lifespan in vivo and biodegrade in 4 weeks. Benefiting from the stable bonding between ionophores and nanoparticles, the biodegradable sensor exhibits a good biocompatibility after degradation. Moreover, this approach of bonding active molecules on bioinert nanoparticles can serve as an effective methodology for minimizing health concerns about biodegradable chemical sensors.

Novel efficient capture of hexavalent chromium by polyethyleneimine/amyloid fibrils/polyvinyl alcohol aerogel beads: Functional design, applicability, and mechanisms.

The harmful effects of hexavalent chromium (Cr(VI)) on the environment and human health have aroused wide public concern. In this study, bulk spherical aerogel beads (PAP) were synthesized from polyethyleneimine (PEI), protein amyloid fibrils (AFL), and polyvinyl alcohol (PVA) through green technology and its removal of Cr(VI) from wastewater was comprehensively studied. The results showed that although the bulk PAP beads (∼ 5 mm) only had an average pore size of 16.88 nm and a BET surface area of 12 m2/g, its maximum adsorption capacity for Cr(VI) reached 121.44 mg/g (at 298 K). Cr(VI) adsorption onto PAP conformed to pseudo-second-order adsorption kinetics and was endothermic. The adsorption of Cr(VI) decreased stepwise with the increase of solution alkalinity (pH = 2: 91.97%; pH = 10: 0.04%). Importantly, PAP showed high selectivity towards Cr(VI) in mixed heavy metal solutions (Cr(VI) > Pb(II) > Ni(II) > Cu(II) > Cd(II)) and good reusability (removal efficiency > 88% after 5 cycles). PAP had excellent anti-interference ability against FA and HCO3- with the overall removal rate exceeding 87% in the presence of 5 - 25 mg/L of these ions. Cations such as Na+, Mg2+, and other heavy metal ions at high concentrations could promote the removal efficiency of Cr(VI). The removal rates of Cr(VI) and Cr(III) by PAP in a tannery wastewater were 34.4% and 59.3%, respectively. Meanwhile, the removal rates of Cr(VI) in a electroplating wastewater and a contaminated soil leachate reached 84.4∼89.7%, showing high practicability. Mechanism studies revealed that electrostatic attraction, hydrogen bonding, reduction, and complexation were the main reactions for Cr(VI) removal by PAP. In general, the study of PAP provides a new insight into using bulk monolith materials for treating Cr(VI) contaminated wastewater.

Stabilization of Bio-Oss® particulates using photocurable hydrogel to enhance bone regeneration by regulating macrophage polarization.

Bone substitutes are widely used in maxillofacial and oral surgeries. However, in clinical practice, bone substitutes with various forms, including separated particulates, powders, and blocks, have exhibited poor handling properties and space maintenance characteristics, resulting in long surgery procedures and unstable volume of the newly formed bone. Movable separated particulates with high stiffness have induced local inflammatory responses that hinder bone regeneration. The present study aimed to develop a new method to enhance the stability and operability of bone substitutes commonly used in dentistry by premixing with photocurable hydrogel GelMA. The GelMA-encapsulated particulate had a strong capacity to aggregate separated particulates and firmly attach to the host bone defect after photocuring compared to particulates alone. Additionally, macrophages at the surface of the GelMA-stabilized particulates tended to present a more M2-like phenotype than those at the surface of Bio-Oss®, leading to more MMR+ multinucleated giant cell formation and the induction of blood vessel invasion and new bone formation. In conclusion, this hydrogel-coated bone substitute strategy facilitates bone regeneration with increased operability, a stable volume of osteogenic space, and a favorable osteogenic microenvironment, indicating its potential value in the field of maxillofacial and oral surgeries when bone substitutes are needed.

Comparative pharmacokinetics of six bioactive components of Shen-Wu-Yi-Shen tablets in normal and chronic renal failure rats based on UPLC-TSQ-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Wu-Yi-Shen tablets (SWYST), a Chinese patent medicine consisting of 12 herbal medicines, was formulated by a famous TCM nephrologist, Zou Yunxiang. It is clinically used to improve the symptoms of nausea, vomiting, poor appetite, dry mouth and throat, and dry stool in patients with chronic renal failure (CRF) accompanied by qi and yin deficiency, dampness, and turbidity. SWYST can reduce urea nitrogen, blood creatinine, and urinary protein loss, and increase the endogenous creatinine clearance rate. However, little is known about its pharmacokinetics. AIM OF STUDY: To compare the pharmacokinetics of six bioactive components after oral administration of SWYST in normal and adenine-induced CRF rats. MATERIALS AND METHODS: A method based on ultra-performance liquid chromatography coupled with a triple-stage quadrupole mass spectrometer (UPLC-TSQ-MS/MS) was developed and validated to determine the six bioactive compounds (albiflorin, paeoniflorin, plantagoguanidinic acid, rhein, aloe-emodin, and emodin) in rat plasma. Rat plasma samples were prepared using protein precipitation. Chromatography was performed on an Agilent Eclipse Plus C18 column (3.0 × 50 mm, 1.8 µm) using gradient elution with a mobile phase composed of acetonitrile and water containing 0.1% (v/v) formic acid, while detection was achieved by electrospray ionization MS under the multiple selective reaction monitoring modes. After SWYST administration, rat plasma was collected at different time points, and the pharmacokinetic parameters of six analytes were calculated and analyzed based on the measured plasma concentrations. RESULTS: The UPLC-TSQ-MS/MS method was fully validated for its satisfactory linearity (r ≥ 0.9913), good precisions (RSD <11.5%), and accuracy (RE: -13.4∼13.1%), as well as acceptable limits in the extraction recoveries, matrix effects, and stability (RSD <15%). In normal rats, the six analytes were rapidly absorbed (Tmax ≤ 2 h), and approximately 80% of their total exposure was eliminated within 10 h. Moreover, in normal rats, the AUC0-t and Cmax of albiflorin, plantagoguanidinic acid, and rhein exhibited linear pharmacokinetics within the dose ranges, while that of paeoniflorin is non-linear. However, in CRF rats, the six analytes exhibited reduced elimination and significantly different AUC or Cmax values. These changes may reflect a decreased renal clearance rate or inhibition of drug-metabolizing enzymes and transporters in the liver and gastrointestinal tract caused by CRF. CONCLUSIONS: A sensitive UPLC-TSQ-MS/MS method was validated and used to investigate the pharmacokinetics of SWYST in normal and CRF rats. This is the first study to investigate the pharmacokinetics of SWYST, and our findings elucidate the causes of their different pharmacokinetic behaviors in CRF rats. Furthermore, the results provide useful information to guide further research on the pharmacokinetic-pharmacodynamic correlation and clinical application of SWYST.

Thioether-functionalized porphyrin-based polymers for Hg2+ efficient removal in aqueous solution.

In this paper, thioether-functionalized porphyrin-based polymers (TPPs) were constructed according to two different "bottom-up" and "top-down" strategies and they were applied for Hg2+ capture in aqueous solution. TPP1, which was constructed by one-step polycondensation of 2,5-bis(methylthio) terephthalaldehyde (BMTA) with pyrrole according to the "bottom-up" strategy, owned high Brunauer-Emmett-Teller (BET) surface area (SBET, 554 m2/g), pore volume (Vtotal, 0.32 cm3/g), and S content (16.8%), resulting in high Hg2+ capture (913 mg/g) with high removal efficiency (> 99%). The adsorption mechanism clarified that the strong coordination between the S species and Hg2+ was the main driving force. In comparison, TPP2 and TPP3 were fabricated by the thioether functionalization of the porphyrin-based polymers according to the "top-down" strategy. They showed much lower SBET, Vtotal, and S content for the reason that the post-functionalization process greatly blocked the pores and the functional sites were hardly fully post-functionalized, resulting in much lower Hg2+ capture (555 mg/g and 609 mg/g, respectively). This work reveals the advantage of the "bottom-up" strategy for the construction of the thioether-functionalized polymers and it offers the guidance for the construction of some other thioether-functionalized polymers.

An Anti-Biofouling Flexible Fiber Biofuel Cell Working in the Brain.

Biofuel cell (BFC) that transfers chemical energy into electricity is a promising candidate as an energy-harvesting device for implantable electronics. However, there still remain major challenges for implantable BFCs, including bulky and rigid device structure mismatching with soft tissues such as the brain, and the power output decreases due to the fouling process in a biological environment. Here, a flexible and anti-biofouling fiber BFC working in the brain chronically is developed. The fiber BFC is based on a carbon nanotube fiber electrode to possess small size and flexibility. A hydrophilic zwitterionic anti-biofouling polydopamine-2-methacryloyloxyethyl phosphorylcholine layer is designed on the surface of fiber BFC to resist the nonspecific protein adsorption in a complex biological environment. After implantation, the fiber BFC can achieve a stable device/tissue interface, along with a negligible immune response. The fiber BFC has first realized power generation in the mouse brain for over a month, exhibiting its promising prospect as an energy-harvesting device in vivo.

Characterization of Mesenchymal Stem Cells Derived from Bisphosphonate-Related Osteonecrosis of the Jaw Patients' Gingiva.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition that specifically occurs in the oral cavity, characterized by retarded wound healing in oral mucosa accelerating the exposure of bone. Moreover, the pathological mechanism remains poorly understood. Gingival mesenchymal stem cells (GMSCs) play a critical role in gingival healing and soft tissue regeneration. Although previous studies have showed that bisphosphonates (BPs) are highly toxic to healthy GMSC, there is overall lack of direct evidence demonstrating the characterization of GMSCs derived from BRONJ patients. In present study, we isolated GMSCs for the first time from the central area of BRONJ patients' gingiva (center-BRONJ GMSCs) and the peripheral area (peri-BRONJ GMSCs), and found that they exhibited decreased proliferation, adhesion, migration capacities and underwent early apoptosis in vitro compared control GMSCs. Notably, the central and peripheral BRONJ GMSCs transplantation in a mice excisional skin model also displayed lower cell survival rate and poor healing effects than that of controls. Mechanistically, TGF-ß1 signaling pathway was suppressed not only in BRONJ patients' gingival lesions but also in BRONJ GMSCs transplantation animal model. The results above suggested that under the microenvironment of BRONJ patients, the dysfunction of GMSCs and the suppressed TGF-ß1 signaling pathway may be the vital factors in impaired gingival healing, thus contributing to persistent exposure of underlying bone and development of BRONJ. This study provides new insights into the prevention for BRONJ by improving the functions of GMSCs and upregulating TGF-ß1 in accelerating gingival wound healing. Schematic illustration of the dysfunction of BRONJ GMSCs in vitro and BRONJ GMSCs transplantation in a mice skin model delaying cutaneous wound healing mainly via suppressing TGF-ß1 signaling pathway.

Multidynamic Osteogenic Differentiation by Effective Polydopamine Micro-Arc Oxide Manipulations.

Introduction: The nanostructural modification of the oral implant surface can effectively mimic the morphology of natural bone tissue, allowing osteoblasts to achieve both proliferation and differentiation capabilities at the bone interface of the dental implant. To improve the osteoinductive activity on the surface of titanium implants for rapid osseointegration, we prepared a novel composite coating (MAO-PDA-NC) by micro-arc oxidation technique and immersion method and evaluated the proliferation, adhesion, and osteogenic differentiation of osteoblasts on this coating. Methods: The coatings were prepared by micro-arc oxidation (MAO) technique and immersion method, and characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM) for different coatings; the loading of PDA was examined using Fourier transform infrared spectroscopy (FTIR); the ion release capacity of the coatings was determined by inductively coupled plasma emission spectrometry (ICP-OES); the interfacial bonding of the coatings was examined using nanoscratch experiment strength. The cytotoxicity of the coating was examined by live/dead staining kit; cell proliferation viability was examined by CCK-8 kit; adhesion and osteogenic effect of the coating were examined by immunofluorescence staining and RT-PCR; osteogenic differentiation was examined by alkaline phosphatase staining. Results: The surface morphology of titanium implants was modified by micro-arc oxidation technology, and a new MAO-PDA-NC composite coating was successfully prepared. The results showed that the MAO-PDA-NC coating not only optimized the physical and chemical properties of the titanium implant surface but also significantly stimulated the biological properties of osteoblast adhesion, proliferation, and osteogenic differentiation on the coating surface. Conclusion: These results show that MAO-PDA-NC composite coating can significantly improve the surface properties of titanium implants and achieve a stable bond between implant and bone tissue, thus accelerating early osseointegration.

Periodontitis aggravates kidney injury by upregulating STAT1 expression in a mouse model of hypertension.

Periodontitis is an autoimmune disease of periodontal tissues initiated by plaque. It is known that there is a close connection between periodontitis and CKD with hypertension, but the underlying mechanisms are unknown. STAT1 has been reported to play a regulatory role in hypertension and chronic kidney disease (CKD). Here, we investigated whether STAT1 regulates periodontitis-mediated aggravation of kidney injury with accompanying hypertension. A hypertensive renal injury mouse model was established with Nos3 knockout mice, and a periodontitis model was established by implantation with the oral bacteria Porphyromonas gingivalis. The mice were intraperitoneally injected with a STAT1 inhibitor. Periodontitis aggravated kidney injury in hypertensive mice, and upregulation of STAT1 was observed when both periodontitis and hypertension were present; furthermore, STAT1 inhibitor moderated this effect. Moreover, we observed that periodontitis promoted the upregulation of inflammatory and fibrosis gene expression in the kidneys of hypertensive mice. In addition, STAT1 inhibition decreased the expression of pro-inflammatory and pro-fibrotic cytokines in the kidney lesion area. Periodontitis augmented the expression of inflammatory and fibrosis genes by upregulating the expression of STAT1, thereby aggravating kidney injury in the hypertensive mouse model.