Biomechanical Analysis of Different Framework Design, Framework Material and Bone Density in the Edentulous Mandible With Fixed Implant-Supported Prostheses: A Three-Dimensional Finite Element Study.

PURPOSE: The objective of this finite element study was to investigate the effect of different framework designs, framework materials, and bone densities on the stress distribution of fixed implant-supported prostheses for edentulous mandibles. MATERIALS AND METHODS: Under the condition of 2-mm cortical bone, 16 models were created in the edentulous mandible to simulate different framework designs (1-piece or 3-piece frameworks) with different framework material (pure titanium, zirconia, polyetheretherketone, or carbon fiber-reinforced polyetheretherketone) in-high or low-density trabecular bone. Then, vertical loading and oblique loading at 75° were applied to the anterior and posterior regions. The stress distribution and stress concentration region of implant and peri-implant bone with different combinations were compared by finite element analysis. RESULTS: The use of the 1-piece zirconia framework in high-density trabecular bone improved stress distribution on implants and peri-implant bone. The region of stress concentration is located in the buccal cervix of the distal implants and the distobuccal portion of the cortical bone in all models. To improve the stress distribution on fixed implant-supported dentures for edentulous mandibles, the 1-piece framework and zirconia represent the better combination. CONCLUSION: Under the condition of 2-mm cortical bone thickness, the full-arch zirconia framework had minimum von Mises stress on implants and peri-implant bone in all models, and high trabecular bone density greatly decreased the stress on cortical bone.

Evaluation of 1-Piece Versus 3-Piece Framework Designs for the Edentulous Mandible with Fixed Implant-Supported Prostheses: A Clinical, Occlusal and Biomechanical Study.

PURPOSE: This study aims to evaluate the clinical, occlusal and biomechanical performance of 1-piece and 3-piece designs for implant-supported fixed dentures in the edentulous mandible. MATERIALS AND METHODS: A total of 65 patients with edentulous mandibles who underwent fixed implant-supported restorations were recruited and subsequently assigned to 1 of 2 groups based on the framework design (1-piece or 3-piece). The participants underwent clinical and occlusal examination using a periodontal probe, T-Scan III system, and electromyography 12 months after prosthesis delivery. Two mandibular finite element models were created to evaluate stress values and their distribution during function. RESULTS: Ninety-five point four percent (n = 62) of participants in the follow-up period underwent clinical and occlusal examination after prosthesis delivery. Clinical examination revealed a trend towards increased inflammation around the implants in the 1-piece prostheses. Occlusal parameters indicated that the 1-piece design was superior for the masticatory system than the 3-piece design. Biomechanical analysis revealed the highest stress values in the posterior region of the 3-piece design. CONCLUSIONS: On the basis of ease of ensuring oral hygiene, when compared to the 3-piece design, the 1-piece framework design might be the superior therapy for restoring an edentulous mandible, based on occlusal and biomechanical outcomes.

Differential impacts of microplastics on carbon and nitrogen cycling in plant-soil systems: A meta-analysis.

Microplastics (MPs) are widely present in terrestrial ecosystems. However, how MPs impact carbon (C) and nitrogen (N) cycling within plant-soil system is still poorly understood. Here, we conducted a meta-analysis utilizing 3338 paired observations from 180 publications to estimate the effects of MPs on plant growth (biomass, nitrogen content, nitrogen uptake and nitrogen use efficiency), change in soil C content (total carbon (TC), soil organic carbon (SOC), dissolved organic carbon (DOC), microbial biomass carbon (MBC)), C losses (carbon dioxide (CO2) and methane), soil N content (total nitrogen, dissolved organic nitrogen, microbial biomass nitrogen, total dissolve nitrogen, ammonium, nitrate (NO3--N) and nitrite) and nitrogen losses (nitrous oxide, ammonia (NH3) volatilization and N leaching) comprehensively. Results showed that although MPs significantly increased CO2 emissions by 25.7 %, they also increased TC, SOC, MBC, DOC and CO2 by 53.3 %, 25.4 %, 19.6 % and 24.7 %, respectively, and thus increased soil carbon sink capacity. However, MPs significantly decreased NO3--N and NH3 volatilization by 14.7 % and 43.3 %, respectively. Meanwhile, MPs significantly decreased plant aboveground biomass, whereas no significant changes were detected in plant belowground biomass and plant N content. The impacts of MPs on soil C, N and plant growth varied depending on MP types, sizes, concentrations, and experimental durations, in part influenced by initial soil properties. Overall, although MPs enhanced soil carbon sink capacity, they may pose a significant threat to future agricultural productivity.

Integrating anaerobic acidification with two-stage forward osmosis concentration for simultaneously recovering organic matter, nitrogen and phosphorus from municipal wastewater.

In order to meet the demand of municipal wastewater for low-carbon treatment and resource recovery, a novel process of anaerobic acidification membrane bioreactor (AAMBR) assisted with a two-stage forward osmosis (FO) (FO-AAMBR-FO) was developed for simultaneously recovering organic matter and nutrients from municipal wastewater. The results indicated that the first FO process concentrated the municipal wastewater to one tenth of the initial volume. The corresponding chemical oxygen demand (COD), ammonia nitrogen (NH4+-N) and total phosphorus (TP) concentration reached up to 2800, 200 and 33 mg/L, respectively. Subsequently, the AAMBR was operated at pH value of 10 for treating the concentration of municipal wastewater, in which the organic matter was successfully converted to acetic acid and propionic acid with a total volatile fatty acids (VFAs) concentration of 1787 mg COD/L and a VFAs production efficiency of 62.36 % during 47 days of stable operation. After that, the NH4+-N and TP concentration in the effluent of the AAMBR were further concentrated to 175 and 36.7 mg/L, respectively, by the second FO process. The struvite was successfully recovered with NH4+-N and TP recovery rate of 94.53 % and 98.59 %, respectively. Correspondingly, the VFAs, NH4+-N and TP concentrations in the residual solution were 2905 mg COD/L, 11.8 and 7.92 mg/L, respectively, which could be used as the raw material for the synthesis of polyhydroxyalkanoate (PHA). Results reported here demonstrated that the FO-AAMBR-FO is a promising wastewater treatment technology for simultaneous recovery of organic matter (in form of VFAs) and nutrients (in form of struvite).

A large scale 16S ribosomal RNA gene amplicon dataset of hand, foot and mouth patients and healthy individuals.

There is evidence linking hand, foot and mouth disease (HFMD) to gut microbiota dysbiosis, and this relationship was corroborated in a large HFMD patient population in our previous study. Here, we present a bacterial 16S rRNA gene dataset from faecal samples of 713 individuals (254 HFMD patients, 459 healthy controls) aged 2 to 7 years residing in Heyuan and Jiangmen counties, Guangdong Province, southern China. Microbiome analysis indicated a significant increase in genus Prevotella, Cetobacterium, and Megamonas was observed in patients with HFMD, whereas a large increase in genus Bacteroides, Ruminococcus, and Faecalibacterium were seen in the control group. We also share the bioinformatic analytical pipeline for this analysis, from data preprocessing to data filtering and amplicon sequence variant (ASV) table generation. We expect that the dataset will be reprocessed, evaluated and fully analysed with various analysis methods to further elucidate the role of the gut microbiota in HFMD development.

Intracellular Self-Immolative Polyprodrug with Near-Infrared Light Guided Accumulation and in Vivo Visualization of Drug Release.

The selective accumulation and real-time monitoring of drug release at tumor site are the key bottlenecks to the clinical translation of polyprodrug. Herein, an intracellular self-immolative polyprodrug (PMTO) is exploited, which not only shows the enhanced cellular internalization and selective accumulation in tumor site under the mild hyperthermia triggered by laser irradiation, but also possesses the self-monitoring drug release ability in vivo. The polyprodrug amphiphiles are synthesized by sequential esterification reaction, and hydrophilic poly(ethylene glycol) serves as blocking agent. On account of the mild hyperthermia produced by PMTO under the laser irradiation at tumor site, the cell membranous permeability increases, resulting in the enhanced cellular internalization and drug accumulation in tumor. After internalized by cells, the self-immolative PMTO nanoparticles can release free mitoxantrone (MTO) in intracellular reductive environment, and ratiometric photoacoustic imaging based on distinct signals between MTO and PMTO is presented to trace the drug release in vivo. Finally, this self-monitoring polyprodrug presents significant tumor suppression efficacy, which exhibits great potential for guiding the clinical medication in cancer treatment.

Synbiotics Supplements Lower the Risk of Hand, Foot, and Mouth Disease in Children, Potentially by Providing Resistance to Gut Microbiota Dysbiosis.

Background: Hand, foot and mouth disease (HFMD) is an acute enterovirus-induced disease. Gut microbiota dysbiosis has been identified as a factor that plays an important role in enteral virus infection, but the gut microbiota profile in hand, foot and mouth disease has rarely been studied in a large population. Methods: A total of 749 children (HFMD: n = 262, healthy control: n = 487) aged 2 to 7 years were recruited from hospitals and communities in the period from May to July, 2017. Clinical and demographical information was collected by trained personnel, and fecal samples were collected and processed for 16S ribosomal RNA(rRNA) gene sequencing. Results: We observed a significant alteration in the microbiota profile of children with HFMD compared with that of control children. Patients with enteroviruses A71(EV71) positive had more dysbiotic gut microbiota than those with coxsackievirus A16 (CAV16) positive. We found that Prevotella and Streptococcus were enriched in children with HFMD, whereas beneficial bacteria, including Bifidobacterium and Faecalibacterium, were depleted. Children with synbiotics supplements had lower risk of HFMD and we observed that the gut microbiota of HFMD patients who were administered synbiotics exhibited potential resistance to the dysbiosis detected in HFMD. Conclusions: This study suggested that the gut microbiota of patients with hand, foot and mouth disease exhibits dysbiosis and that synbiotics supplements potentially helps maintain the homeostasis of the gut flora.

Effects of PEGylation on capture of dextran-coated magnetic nanoparticles in microcirculation.

BACKGROUND: Magnetic nanoparticles (MNPs) can be localized against hemodynamic forces in blood vessels with the application of an external magnetic field. In addition, PEGylation of nanoparticles may increase the half-life of nanocomposites in circulation. In this work, we examined the effect of PEGylation on the magnetic capture of MNPs in vivo. METHODS: Laser speckle contrast imaging and capillaroscopy were used to assess the magnetic capture of dextran-coated MNPs and red blood cell (RBC) flow in cremaster microvessels of anesthetized rats. Magnetic capture of MNPs in serum flow was visualized with an in vitro circulating system. The effect of PEGylation on MNP-endothelial cell interaction was studied in cultured cells using an iron assay. RESULTS: In microcirculation through cremaster muscle, magnet-induced retention of 250 nm MNPs was associated with a variable reduction in RBC flow, suggesting a dynamic coupling of hemodynamic and magnetic forces. After magnet removal, faster restoration of flow was observed in PEG(+) than PEG(-) group, which may be attributed to a reduced interaction with vascular endothelium. However, PEGylation appears to be required for magnetic capture of 50 nm MNPs in microvessels, which was associated with increased hydrodynamic diameter to 130±6 nm in serum, but independent of the ς-potential. CONCLUSION: These results suggest that PEGylation may enhance magnetic capture of smaller MNPs and dispersion of larger MNPs after magnet removal, which may potentially affect the targeting, pharmacokinetics and therapeutic efficacy.

Isolation of Single Intracellular Bacterial Communities Generated from a Murine Model of Urinary Tract Infection for Downstream Single-cell Analysis.

In this article, we outline a procedure used to isolate individual intracellular bacterial communities from a mouse that has been experimentally infected in the urinary tract. The protocol can be broadly divided into three sections: the infection, bladder epithelial cell harvesting, and mouth micropipetting to isolate individual infected epithelial cells. The isolated epithelial cell contains viable bacterial cells and is nearly free of contaminating extracellular bacteria, making it ideal for downstream single-cell analysis. The time taken from the start of infection to obtaining a single intracellular bacterial community is about 8 h. This protocol is inexpensive to deploy and uses widely available materials, and we anticipate that it can also be utilized in other infection models to isolate single infected cells from cell mixtures even if those infected cells are rare. However, due to a potential risk in mouth micropipetting, this procedure is not recommended for highly infectious agents.

The effect of direct translocation across endosomes on the cytotoxicity of the recombinant protein e23sFv-Fdt-casp6 to HER2 positive gastric cancer cells.

HER2-positive cancers represent a class of malignancies with high metastasis and poor prognosis. We previously generated the e23sFv-PEA II-casp6 recombinant, which contains an anti-HER2 single-chain antibody (e23sFv), a Pseudomonas exotoxin A translocation domain (PEA II), and a constitutively active caspase-6 (casp6), and demonstrated its potent selective anti-tumor activities. In this study, we generated a smaller-sized recombinant e23sFv-Fdt-casp6, in which the PEA II domain was replaced with the furin cleavage sequence from diphtheria toxin (Fdt), and explored its translocation pathway and specific killing mechanism. We found that e23sFv-Fdt-casp6 proteins, following their receptor-mediated endocytosis in HER2-positive gastric cancer cells, underwent furin-mediated cleavage in endosome and engaged in direct translocation of the released C-terminal fragment (active caspase-6) instead of via the trans-Golgi and the endoplasmic reticulum (ER) pathway. The active caspase-6 cleaved its well-documented substrate, Lamin A, and subsequently triggered the apoptosis of cancer cells. The e23sFv-Fdt-casp6 proteins produced from genetically modified cells showed a selective cytotoxicity to cultured HER2-positive gastric cancer cells. Similar to the results of our previous research on e23sFv-PEA II-casp6, the delivery of liposome-encapsulated e23sFv-Fdt-casp6 constructs in tumor-adjacent muscles also inhibited tumor growth and prolonged animal survival in a nude mouse xenograft tumor model. Moreover, e23sFv-Fdt-casp6 proteins were also cytotoxic to trastuzumab-resistant gastric cancer cells characterized by downregulated HER2 expression. Accordingly, e23sFv-Fdt-casp6 recombinant provides a promising therapeutic alternative for HER2-positive and trastuzumab-resistant gastric cancers.

A caspase-6 and anti-human epidermal growth factor receptor-2 (HER2) antibody chimeric molecule suppresses the growth of HER2-overexpressing tumors.

Clinical studies have suggested that human epidermal growth factor receptor-2 (HER2) provide a useful target for antitumor therapy. We previously described the generation of a chimeric HER2-targeted immunocasp-3 protein. In this study, we extend the repertoire of chimeric proapoptotic proteins with immunocasp-6, a construct that comprises a HER2-specific single-chain Ab, a single-chain Pseudomonas exotoxin A, and an active caspase-6, which can directly cleave lamin A leading to nucleus damage and inducing programmed cell death. We demonstrate that the secreted immunocasp-6 molecule selectively recognizes and induces apoptosis in HER2-overexpressing tumor cells in vitro, but not in cells with undetectable HER2. The immunocasp-6 gene was next transferred into BALB/c athymic mice bearing human breast SK-BR-3 tumors by i.m. injection of liposome-encapsulated vectors, by intratumor injection of adenoviral vectors, or by i.v. injection of PBMC modified by retroviral infection. Regardless of the method used, expression of immunocasp-6 suppressed tumor growth and prolonged animal survival significantly. Our data show that the chimeric immunocasp-6 molecule can recognize HER2-positive tumor cells, promptly attack their nucleus, and induce their apoptotic death, suggesting the potential of this strategy for the treatment of human cancers that overexpress HER2.