Analysis of the sagittal root angle and its correlation with hard and soft tissue indices in anterior teeth for immediate implant evaluation: a retrospective study.

BACKGROUND: To assess the root angle characteristics of maxillary incisors, and to analyze the relationship between the root angle and other implant-related anatomical indices to use the sagittal root angle as an index for immediate implant evaluation and design. METHODS: A random sample consisting of 400 cone-beam computed tomography (CBCT) images and 65 maxillary plaster models were selected for the present study. CBCT and stereolithography (STL) scan images were imported as DICOM files into coDiagnostiX software for matching the hard and soft tissue. The angle between the long axis of the anterior tooth and the corresponding alveolar bone and implant-related hard and soft tissue indices were measured in the sagittal section. Descriptive statistics, frequency analysis, multi-level comparisons, and correlation analyses were performed. RESULTS: The average sagittal root angles were 15° at the central incisor and 19° at the lateral incisor. The root angle in males was significantly larger than that in females, and increased with age. The largest angle, 22.35°, was found in the lateral incisors of the oldest (> 50 years old) male group. The root angle was found to correlate with coronal buccal bone thickness, coronal palatal bone thickness, apical buccal bone thickness, palatal bone thickness, and the below apex bone thickness. CONCLUSIONS: The sagittal root angle could reflect the distribution of other implant-related anatomical indices, which may provide additional reference for the evaluation of immediate implant placement.

An intelligent detecting system for permeability prediction of MBR.

The membrane bioreactor (MBR) has been widely used to purify wastewater in wastewater treatment plants. However, a critical difficulty of the MBR is membrane fouling. To reduce membrane fouling, in this work, an intelligent detecting system is developed to evaluate the performance of MBR by predicting the membrane permeability. This intelligent detecting system consists of two main parts. First, a soft computing method, based on the partial least squares method and the recurrent fuzzy neural network, is designed to find the nonlinear relations between the membrane permeability and the other variables. Second, a complete new platform connecting the sensors and the software is built, in order to enable the intelligent detecting system to handle complex algorithms. Finally, the simulation and experimental results demonstrate the reliability and effectiveness of the proposed intelligent detecting system, underlying the potential of this system for the online membrane permeability for detecting membrane fouling of MBR.

The potential efficacy of R8-modified paclitaxel-loaded liposomes on pulmonary arterial hypertension.

PURPOSE: In this paper, a novel liposomal formulation of paclitaxel modified with octaarginine (R8) was fabricated and the therapeutic efficacy of it on pulmonary arterial hypertension was evaluated. METHODS: Octaarginine-modified stealth liposomes loaded with PTX (R8-PTX-LIP) were prepared and characterized. Vector cytoxicity and anti-proliferation ability of different formulations on primary cultured VSMCs were determined with MTT assay. The uptake capacity of VSMCs on different formulations were evaluated by flow cytometry, and the influences on cytoskeletons of liposomes were investigated by cytoskeleton staining with rhodamine-phalloidin. The biodistribution of liposomes were imaged by a CCD camera using a near-infrared fluorophore DiD. The therapeutic efficacy of different PTX-formulations of PAH was evaluated by hemodynamic measurement, right ventricular hypertrophic parameters and vessel diameters. RESULTS: The cellular uptake of R8 modified liposomes (R8-LIP) was improved noticeably compared with other groups. All liposomes did not exert cytotoxicity on VSMCs in 24 h. R8-PTX-LIP exhibited the strongest inhibitory effect on the proliferation of VSMCs among all the formulations (p < 0.001). R8-PTX-LIP could reverse the phenotype transformation, and inhibit cell migration. mPAP, (RV/LV+S) and the wall thickness of small distal pulmonary arteries of rats treated with R8-PTX-LIP were significantly lower than those from other groups (p < 0.001). CONCLUSIONS: In conclusion, the drug delivery system of R8-modified paclitaxel-loaded liposomes we established showed pronounced inhibitory effect over VSMCs proliferation and cytoskeleton formation in vitro, a stronger pulmonary delivery ability in vivo, and was effective on PAH, showing the potential for pulmonary drug delivery system for PAH treatment.

Preparation of an Ultrahigh-DAR PDL1 monoclonal antibody-polymeric-SN38 conjugate for precise colon cancer therapy.

Antibody-drug conjugates (ADCs) are the most potent active tumor-targeting agents used clinically. However, the preparation of ADCs with high drug-to-antibody ratios (DARs) remains a major challenge. Herein, a Fab-nondestructive SN38-loaded antibody-polymeric-drug conjugate (APDC), aPDL1-NPLG-SN38, was prepared that had a DAR as high as 72 for the first time, by increased numbers of payload binding sites via the carboxyl groups of poly (l-glutamic acid) (PLG). The bonding of Fc-III-4C peptide with PLG-graft-mPEG/SN38 (Fc-NPLG-SN38) was achieved using a click reaction between azide and DBCO groups. The aPDL1-NPLG-SN38 conjugate was then synthesized by the high-affinity interaction between the Fc-III-4C peptide in Fc-NPLG-SN38 and the crystallizable fragment (Fc) of PDL1 monoclonal antibody (aPDL1). This approach avoided the potential deleterious effects on the Fab structure of the monoclonal antibody. The aqueous environment used in its preparation helped maintain monoclonal antibody recognition capability. Through the specific recognition by aPDL1 of PDL1 that is highly expressed on MC38 tumors, the accumulation of aPDL1-NPLG-SN38 in the tumors was 2.8-fold greater than achieved with IgG-NPLG-SN38 that had no active tumor-targeting capability. aPDL1-NPLG-SN38 exhibited excellent therapeutic properties in both medium-sized and large MC38 tumor animal models. The present study provides the details of a novel preparation strategy for SN38-loaded ADCs having a high DAR.

Design, preparation and adsorption performances of norfloxacin molecularly imprinted polymers.

Here, norfloxacin (NOR) molecularly imprinted polymers (MIPs) exhibiting improved adsorption and selectivity properties were prepared via simulation and experiment. NOR and methacrylic acid (MAA) were employed as the imprinting molecule and functional monomer, respectively. The imprinting ratio, as well as cross-linking agents of the NOR-MIPs, had been optimised via the LC-ωPBE/6-31G(d,p) method. The nature and mechanism of the interaction between MIPs and MAA, as well as the selectivity of the NOR-MAA stable complex (1:1), were also discussed. Based on the simulation results, the effects of the different imprinting ratios and cross-linking agents on the adsorption of NOR-MIPs were also investigated. Concurrently, the affinity, selectivity and stability of NOR-MIPs were analysed via dynamic, static and selective adsorption, as well as thermogravimetry. The calculated and experimental results demonstrated that the stable complexes comprising NOR and MAA were formed via hydrogen bonding. The complex comprising NOR and MAA in an interaction ratio of 1:6 exhibited the highest number of hydrogen bonds and the lowest binding energy. Trihydroxymethylpropyl trimethylacrylate was more appropriate for the synthesis of NOR-MIPs compared with the two other cross-linking agents. NOR-MIPs achieved the excellent selective adsorption of NOR in single and multiple adsorption systems. This design and synthesis strategy availed a new idea for the efficient preparation of s with specific adsorption performance.

Human Saliva Metabolome for Oral Lichen Planus Biomarker Identification.

BACKGROUND: Oral Lichen Planus (OLP) is one of the most common oral mucosal diseases. However, the current diagnostic method for OLP has limitations, and sometimes it is easy to be misdiagnosed. Salivary metabolomics may provide new ideas for the diagnosis of OLP. OBJECTIVE: To identify the biomarkers for the early detection of OLP. METHODS: A non-targeted metabolomic analysis method was established based on UHPLC-Q-Orbitrap HRMS (Ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry) to analyze the differential metabolites in saliva samples of patients with OLP and healthy subjects. Saliva samples were collected from 120 OLP patients and 125 healthy subjects. RESULTS: A total of 19 differential metabolites were identified, including 6 amino acid metabolites, 2 carnitines, 2 lipid metabolites and 9 other metabolites. The integrated biomarkers were constructed by 3 metabolites according to Receiver Operating Characteristic (ROC). Meanwhile, multiple metabolic pathways were found to be involved in the occurrence and development of OLP. CONCLUSION: Metabolomics can be used to characterize the characteristics of metabolic disorders in patients with OLP, which is also helpful to the early diagnosis of OLP and reveal the pathological process of OLP.

Harnessing X-Ray Energy-Dependent Attenuation of Bismuth-Based Nanoprobes for Accurate Diagnosis of Liver Fibrosis.

Timely detection of liver fibrosis by X-ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X-ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X-ray attenuation characteristics of the scanned matter. Herein, an X-ray energy-dependent attenuation strategy originated from bismuth (Bi)-based nanoprobes (BiF3 @PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3 @PDA@HA can exhibit characteristic attenuation depending on different levels of X-ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3 @PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3 @PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy-dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging-based disease diagnosis.

Modulating the cobalt dose range to manipulate multisystem cooperation in bone environment: a strategy to resolve the controversies about cobalt use for orthopedic applications.

The paradoxical effect of cobalt on biological processes has aroused controversy regarding the application of cobalt-based biomaterials in bone regeneration. Tuning the dose range of cobalt ions may be a valid strategy to resolve the controversies about cobalt use for orthopedic applications. Recent progress in bone biology has highlighted the effects of multisystem cooperation (especially of osteoimmune, skeletal, and vascular systems) on bone dynamics. Before the application of this dose-tuning strategy, a deeper understanding of its dose-dependent effect on the cooperation of osteoimmune, skeletal, and vascular systems is needed. However, due to the difficulties with investigating the interaction of multiple systems in vitro, the multimodal effects of cobalt on bone homeostasis were investigated here, in an in vivo scenario. Methods: In vitro CCK8 assay and cytoskeletal staining were preformed to detecte the cell cytotoxic reaction in response to 0.1-100 ppm cobalt stimulation. Blood clot containing 0.1 to 5 ppm of cobalt were implanted in the rat calvarium defect. The gene profile of osteoimmune, skeletal, and vascular system as well as the systemic toxicity were evaluated via RT-qPCR, histological analysis and inductively coupled plasma mass spectrometry. The bone regeneration, osteoclastogenesis and vascularization were assessed by micro-ct and histological analysis. Results: Cobalt concentration below 5 ppm did not cause cell toxicity in vitro. No systemic toxicity was observed in vivo at 0.1-5 ppm cobalt concentration. It was found that the early cytokine profiles of the multiple interacting systems were different in response to different cobalt doses. Most of the anti-inflammatory, osteogenic, and proangiogenic factors were upregulated in the 1 ppm cobalt group at the early stage. In the late stage, the 1ppm group was most superior in bone regenerative effect while the 5 ppm group displayed the strongest osteoclastogenesis activity. Conclusions: The 1 ppm concentration of cobalt yielded the most favorable cooperation of the osteoimmune, skeletal, and vascular systems and subsequently optimal bone regeneration outcomes. Tuning the cobalt dose range to manipulate the cooperation of osteoimmune, skeletal, and vascular systems could be a promising and valuable strategy to prevent paradoxical effects of cobalt while preserving its beneficial effects.

A standardized rat burr hole defect model to study maxillofacial bone regeneration.

With high incidence rate and unique regeneration features, maxillofacial burr hole bone defects require a specially designed bone defect animal model for the evaluation of related bone regenerative approaches. Although some burr hole defect models have been developed in long bones or calvarial bones, the mandible has unique tissue development origins and regenerative environments. This suggests that the defect model should be prepared in the maxillofacial bone area. After dissecting the anatomic structures of rat mandibles, we found that creating defects in the anterior tooth area avoided damaging important organs and improved animal welfare. Furthermore, the available bone volume at the anterior tooth area was superior to that of the posterior tooth and ascending ramus areas. We then managed to standardize the model by controlling the age, weight and gender of the animal, creating standardized measurement instruments and reducing the variations derived from various operators. We also succeeded in deterring the self-rehabilitation of the proposed model by increasing the defect size. The 6 × 2 mm and 8 × 2 mm defects were found to meet the requirements of bone regenerative studies. This study provided a step-by-step standardized burr hole bone defect model with minimal tissue damage in small animals. The evaluations resulting from this model testify to the in vitro outcomes of the proposed regenerative approaches and provide preliminary screening data for further large animal and clinical trials. Therefore, the inclusion of this model may optimize the evaluation systems for maxillofacial burr hole bone defect regenerative approaches. STATEMENT OF SIGNIFICANCE: Unremitting effort has been devoted to the development of bone regenerative materials to restore maxillofacial burr hole bone defects because of their high clinical incidence rate. In the development of these biomaterials, in vivo testing in small animals is necessary to evaluate the effects of candidate biomaterials. However, little has been done to develop such defect models in small animals. In this study, we developed a standardized rat mandible burr hole bone defect model with minimal injury to the animals. A detailed description and supplementary video were provided to guide the preparation. The development of this model optimizes the maxillofacial bone regenerative approach evaluation system.

π-Extended Benzoporphyrin-Based Metal-Organic Framework for Inhibition of Tumor Metastasis.

We report on the benzoporphyrin-based metal-organic framework (TBP-MOF), with 10-connected Zr6 cluster and much improved photophysical properties over the traditional porphyrin-based MOFs. It was found that TBP-MOF exhibited red-shifted absorption bands and strong near-infrared luminescence for bioimaging, whereas the π-extended benzoporphyrin-based linkers of TBP-MOF facilitated 1O2 generation to enhance O2-dependent photodynamic therapy (PDT). It was demonstrated that poly(ethylene glycol)-modified nanoscale TBP-MOF (TBP-nMOF) can be used as an effective PDT agent under hypoxic tumor microenvironment. We also elucidated that the low O2-dependent PDT of TBP-nMOF in combination with αPD-1 checkpoint blockade therapy can not only suppress the growth of primary tumor, but also stimulate an antitumor immune response for inhibiting metastatic tumor growth. We believe this TBP-nMOF has great potential to serve as an efficient photosensitizer for PDT and cancer immunotherapy.

Numerical optimization of membrane module design and operation for a full-scale submerged MBR by computational fluid dynamics.

The hydrodynamics in the membrane module of a full-scale sMBR at 500 m3/d was simulated by computational fluid dynamics (CFD) in this study. Several key indexes, including membrane distance (d), aeration design, height of gas-liquid dispersion hm, and freeboard height hf and operational conditions, including SADp and liquid viscosity, were optimized through investigating their impacts on water velocity distribution and membrane shear stress. The CFD model was validated by comparing the simulated trace element RTD curves with experimental results. The optimal design and operational parameters for the full scale sMBR are as following: membrane distance d = 35 mm, air diffusers parallel located 75-100 mm under the bottom of the membrane module, the free board height hf adjusted to 400 mm, and the SADp recommended as 20 in the full-scale MBR studied.

Nanotopography-based strategy for the precise manipulation of osteoimmunomodulation in bone regeneration.

Immune cells play vital roles in regulating bone dynamics. Successful bone regeneration requires a favourable osteo-immune environment. The high plasticity and diversity of immune cells make it possible to manipulate the osteo-immune response of immune cells, thus modulating the osteoimmune environment and regulating bone regeneration. With the advancement in nanotechnology, nanotopographies with different controlled surface properties can be fabricated. On tuning the surface properties, the osteo-immune response can be precisely modulated. This highly tunable characteristic and immunomodulatory effects make nanotopography a promising strategy to precisely manipulate osteoimmunomdulation for bone tissue engineering applications. This review first summarises the effects of the immune response during bone healing to show the importance of regulating the immune response for the bone response. The plasticity of immune cells is then reviewed to provide rationales for manipulation of the osteoimmune response. Subsequently, we highlight the current types of nanotopographies applied in bone biomaterials and their fabrication techniques, and explain how these nanotopographies modulate the immune response and the possible underlying mechanisms. The effects of immune cells on nanotopography-mediated osteogenesis are emphasized, and we propose the concept of "nano-osteoimmunomodulation" to provide a valuable strategy for the development of nanotopographies with osteoimmunomodulatory properties that can precisely regulate bone dynamics.