Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

Osteoimmunology mediators are critical to balance osteoblastogenesis and osteoclastogenesis to maintain bone homeostasis. A lot of the osteoimmunology mediators are regulated by interleukin-20 (IL-20). However, little is known about the role of IL-20 in bone remodeling. Here, we showed that IL-20 expression was correlated with osteoclast (OC) activity in remodeled alveolar bone during orthodontic tooth movement (OTM). Ovariectomize (OVX) in rats promoted OC activity and enhanced IL-20 expression, while blocking OC inhibited IL-20 expression in osteoclasts. In vitro, IL-20 treatment promoted survival, inhibited apoptosis of the preosteoclast at the early stages of osteoclast differentiation, and boosted the formation of osteoclasts and their bone resorption function at the late stages. More importantly, anti-IL-20 antibody treatment blocked IL-20-induced osteoclastogenesis and the subsequent bone resorption function. Mechanistically, we showed that IL-20 synergistically acts with RANKL to activate the NF-κB signaling pathway to promote the expression of c-Fos and NFATc1 to promote osteoclastogenesis. Moreover, we found that local injection of IL-20 or anti-IL-20 antibody enhanced osteoclast activity and accelerated OTM in rats, while blocking IL-20 reversed this phenomenon. This study revealed a previously unknown role of IL-20 in regulating alveolar bone remodeling and implies the application of IL-20 to accelerated OTM.

[Progress in application of Bletilla striata polysaccharide in novel drug delivery systems and biomaterials].

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.

Development and Characterization of PCL Electrospun Membrane-Coated Bletilla striata Polysaccharide-Based Gastroretentive Drug Delivery System.

The purpose of this study was to investigate the potential of Bletilla striata polysaccharide (BSP, a natural glucomannan material) for the development of a gastroretentive drug delivery system for the first time. Novel BSP-based porous wafer was prepared for levofloxacin hydrochloride (LFH) delivery by combining floating, swelling, and mucoadhesion mechanisms. The influences of BSP and ethyl cellulose (EC) on drug release and mucoadhesive strength were studied by 32 factorial design. The optimized matrix was coated with polycaprolactone (PCL) electrospun membrane by electrospinning and heat treatment technology. The optimized formula (F6, coated) exhibited Q4 h of 41.20 ± 1.90%, Q8 h of 76.49 ± 1.69%, and mucoadhesive strength of 86.11 ± 1.33 gf, and its drug release profile most closely resembled the Korsmeyer-Peppas model with anomalous diffusion driving mechanism. F6 (coated) also presented excellent buoyancy, preferred swelling characteristic due to the porous structure formed by freeze-drying. Meanwhile, the internal morphology, physical state, drug-excipient compatibility, and thermal behavior were recorded. The negligible cytotoxicity of F6 (coated) was observed in human gastric epithelial cell cultures. In the in vitro antimicrobial experiment, the prepared wafer exhibited obvious bacterial inhibition zone, and due to its longer gastric retention, the wafer also performed a more effective Helicobacter pylori clearance than free LFH in vivo. Graphical abstract.

[Cases of hepatitis C virus infection with 2i/2a recombination genotype in the Lanzhou area and effects of related genetic variations on interferon alpha response].

OBJECTIVE: To investigate Lanzhou area cases of hepatitis C virus (H-CV) infection with a 5'-non coding region (NCR) 2i genotype and core (C), envelope protein (E) and non-structural protein (NS5) 2a genotype and the relationship with therapeutic response to interferon-alpha (IFNa). METHODS: Nine patients who received IFNa-based treatment for HCV between 2007 and 2009 at the Second People's Hospital of Gansu Province were selected for analysis.Restriction enzyme analysis was carried out for the 5'-NCR and sequencing was carried out for the other gene areas.The relationship between genetic variants and IFNaresponse was examined. RESULTS: Of the total nine HCV cases treated with IFNa-based therapies, five of the patients achieved sustained virological response (SVR), which included two cases with type 2 genotype and three cases with no MboI restriction enzyme point of tangency (i.e.type 1b). The remaining four patients that did not achieve SVR included one case of type 2a, with a 1b and 2a mixed state, and one case with 5'-NCR 2i genotype and C area, NS5 area 2a genotype; the other two cases had 5'-NCR and C area type 1b. Of the five cases with 5'-NCR 2i genotype, all had C 2a genotype and two had C/E 2a and NS5 2a genotypes.The seven patients that showed no response to ordinary IFNa were converted to long-term IFNa plus ribavirin combination antiviral treatment; five (71.4%) of the cases showed response in HCV RNA level and the patients treated with the pegylated form showed greater response. CONCLUSION: HCV genotyping can only provide information on the particular region of gene sequence examined, and it is important to sequence all gene regions where mutations related to antiviral drug response are located. Peg-IFNa-2a combined with ribavirin may achieve better therapeutic effect in patients infected with 2i/2a recombinant forms of HCV.

Fabrication and characterization of PVA@PLA electrospinning nanofibers embedded with Bletilla striata polysaccharide and Rosmarinic acid to promote wound healing.

In this study, a novel nanofiber material with Polylactic acid (PLA), natural plant polysaccharides-Bletilla striata polysaccharide (BSP) and Rosmarinic acid (RA) as the raw materials to facilitate wound healing was well prepared through coaxial electrospinning. The morphology of RA-BSP-PVA@PLA nanofibers was characterized through scanning electron microscopy (SEM), and the successful formation of core-shell structure was verified under confocal laser microscopy (CLSM) and Fourier transform infrared spectroscopy (FTIR). RA-BSP-PVA@PLA exhibited suitable air permeability for wound healing, as indicated by the result of the water vapor permeability (WVTR) study. The results of tension test results indicated the RA-BSP-PVA@PLA nanofiber exhibited excellent flexibility and better accommodates wounds. Moreover, the biocompatibility of RA-BSP-PVA@PLA was examined through MTT assay. Lastly, RA-BSP-PVA@PLA nanofibers can induce wound tissue growth, as verified by the rat dorsal skin wound models and tissue sections. Furthermore, RA-BSP-PVA@PLA can facilitate the proliferation and transformation of early wound macrophages, and down-regulate MPO+ expression of on the wound, thus facilitating wound healing, as confirmed by the result of immunohistochemical. Thus, RA-BSP-PVA@PLA nanofibers show great potential as wound dressings in wound healing.

Chitosan electrospun nanofibers derived from Periplaneta americana residue for promoting infected wound healing.

Periplaneta americana has been used medicinally for years to treat a wide variety of skin lesions or ulcers. However, a sizable portion of the drug residues that are retained after extraction are routinely thrown away, thus posing a hazard to the environment and depleting resources. In this study, low molecular weight Periplaneta americana chitosan (LPCS) and high molecular weight Periplaneta americana chitosan (HPCS) were extracted from Periplaneta americana residue (PAR) based on the conventional acid-base method and two deacetylation methods. Moreover, the physicochemical properties and structural differences between the above two chitosan and commercial chitosan (CS) were compared using different methods. Next, two nanofibers comprising different ratios of Periplaneta americana chitosan (LPCS or HPCS), polyvinyl alcohol (PVA), and polyethylene oxide (PEO) were prepared and optimized. The above nanofibers exhibited excellent mechanical properties, antibacterial properties, and biocompatibility while facilitating wound healing in an infected rat whole-layer wound model by promoting wound closure, epithelialization, collagen deposition, and inflammation reduction. In brief, this study produced an effective and affordable wound dressing and offered a suggestion for the comprehensive utilization of Periplaneta americana residue.

Extraction and characterization of chitosan from Eupolyphaga sinensis Walker and its application in the preparation of electrospinning nanofiber membranes.

Due to its capabilities for wound healing, antimicrobial defense, hemostasis, and biodegradation, chitosan has seen increased use in biomedical disciplines in recent years. In the meantime, efforts have been made to develop and use insect chitosan as a source to address the seasonal, irritating, and regional shortcomings of traditional shrimp and crab chitosan. In this study, a new type of insect chitosan (DCS) was first extracted from Eupolyphaga sinensis Walker by a low-temperature intermittent method and was compared with commercially available pharmaceutical chitosan (CS). Firstly, the degree of deacetylation and molecular weight of DCS were determined, and DCS was characterized by FT-IR, 1H NMR, XRD, and TGA-DTG. On this basis, DCS was mixed with PVA and PEO to create a novel electrospun nanofiber membrane. The air permeability, antibacterial properties, and biocompatibility of the nanofiber membrane were evaluated, as well as the membrane's shape, structure, and mechanical characteristics. Finally, the activity of nanofiber membranes in promoting wound healing was verified with a rat full-thickness skin defect model, hoping to provide a reference for the development of new drug delivery carriers and wound dressings.

pH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide.

Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (ß-amino ester) (QPBAE-C18), were prepared and then characterized. The result indicated that TP/PNPs with the uniform particle size of âˆ¼ 175 nm exhibited the high drug loading capacity and storage stability based on the polymeric charge interaction, in which DLC and DEE of TP/PNPs were obtained as 11.27 ± 0.44 % and 95.23 ± 2.34 %, respectively. Mediated by the "ELVIS" effect of NPs, CD44 receptor-mediated macrophage targeting, and pH-sensitive endo/lysosomal escape under the "proton sponge" effect, TP/PNPs exhibited the enhanced cellular internalization and cytotoxicity while mitigating the inflammation of LPS-activated RAW 264.7 cells. Even after 96-hour after administration, PNPs were preferentially accumulated in the inflammatory joints in a long term. It is noteworthy that after treatment for 14 days with 100 µg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA.

Use and performance of artificial intelligence applications in the diagnosis of chronic apical periodontitis based on cone beam computed tomography imaging.

OBJECTIVES: This study aims to investigate the diagnostic application of an artificial intelligence (AI) computer-aided diagnostic system based on a convolutional neural network algorithm in detecting chronic apical periodontitis in cone beam computed tomography (CBCT) images. METHODS: CBCT raw data of 55 single root chronic apical pe-riodontitis taken in 2nd Dental Center of Peking University School and Hospital from 49 patients from January 2017 to December 2021 were collected, and the chronic apical periodontitis areas were identified by experienced clinicians ma-nually and segmented layer by layer in Materialise Mimics Medical Software. Deep learning of lesion characterization was conducted via AI 3D U-Net, and the network segmentation results were compared manually with the test sets in terms of intersection over union (IOU), Dice coefficient, and pixel accuracy (PA). RESULTS: In our deep learning algorithm, the IOU for all actual true lesions in test set samples was 92.18%, and the Dice coefficient and the PA index were 95.93% and 99.27%, respectively. Lesion segmentation and volume measurements performed by humans and AI systems showed excellent agreement. CONCLUSIONS: AI systems based on deep learning methods can be applied for detecting chronic apical periodontitis on CBCT images in clinical applications.

Photothermal-promoted multi-functional dual network polysaccharide hydrogel adhesive for infected and susceptible wound healing.

A low-cost wound dressing with efficient sterilization and exhibiting long-term antimicrobial activity is required for the absence of antibiotics, particularly for the wound healing of patients with chronic wounds or long-term activities under low sanitary conditions (e.g., battlefield and poverty-stricken areas). Here, a dual dynamic crosslinking hydrogel was introduced. The hydrogel was supported by gallic acid grafted chitosan and oxidized Bletilla striata polysaccharide as the scaffold and formed by two types of dynamic crosslinking: Schiff base, pyrogallol-Fe3+. It exhibited its adhesion, self-healing, good biocompatibility, great intrinsic antibacterial, and near-infrared photothermal conversion activity. In addition, the use of two types of polysaccharides, and the existence of the photothermal effect, making the hydrogel has the functions of accelerating gelation, degradation on-demand, and rapid sterilization. In brief, such cost-effective multifunctional hydrogel could support wound healing in patients prone to bacterial infection, and it has a promising application in the care of infected wounds.

Strategy for osteoarthritis therapy: Improved the delivery of triptolide using liposome-loaded dissolving microneedle arrays.

Osteoarthritis (OA) is a chronic disease that seriously impairs people's physical function and quality of life. Triptolide (TP), as a promising anti-inflammatory drug for the treatment of OA, has limited clinical application due to its severe systemic toxicity, poor solubility and rapid elimination in the body. To extend its application prospect for OA treatment. We have developed a liposome-loaded dissolving microneedle (DMN) system, which can effectively deliver poorly water-soluble TP and improve OA symptoms. To incorporate TP into DMNs, triptolide liposome (TP-Lipo) with entrapment efficiency of 90.25% was prepared by ethanol injection. Subsequently, TP-Lipo was concentrated by ultrafiltration tube and mixed with hyaluronic acid solution to prepare DMNs, TP-Lipo-loaded DMNs (TP-Lipo@DMNs) showed sufficient mechanical and insertion properties to penetrate about 200 µm of rat skin. The drug distribution in vivo showed that TP-Lipo@DMNs had a slow-release effect compared with intra-articular injection. In vivo pharmacodynamic research showed that TP-Lipo@DMNs significantly reduced knee joint swelling and the level of inflammatory cytokines (TNF-α, IL-1ß, IL-6). Micro-CT and histological evaluation showed that TP-Lipo@DMNs effectively reduced cartilage destruction and alleviated OA symptoms. These results support that TP@Lipo@DMNs may be a promising option for OA treatment.

[Comparison of fracture strength of two chairside CAD/CAM ceramic blocs with different thickness].

PURPOSE: To provide theoretical basis for clinical CAD/CAM restorations with a comparison of the fracture strength between two chairside CAD/CAM immediate restorative materials (IPS e.max CAD and Vita Enamic) with different occlusal thickness in vitro. METHODS: IPS e.max CAD and Vita Enamic full-crowns with occlusal thicknesses 1.5/2.0/2.5 mm were fabricated with CEREC and adhesively seated to dies customized by manufacturer (n=42). All specimens were stored in distilled water at 37 ℃ for 24 h. Later, static fractural loading was performed. The fracture surface was observed through scanning electron microscope (SEM) and energy dispersive spectrum (EDS). The composites of two materials were detected by X-Ray diffraction (XRD) techniques. The results of fracture strength were analyzed by one-way ANOVA and t-test via SPSS 20.0 software package. RESULTS: With the increase of occlusal thickness, the fracture strength of IPS e.max CAD increased remarkably. However, the Vita Enamic's fracture strength remained the same with no significant difference. With the occlusal thickness increased from 1.5 to 2.0 mm, there was no significant difference in the fracture strength between IPS e.max CAD group and Vita Enamic group. As the thickness increased from 1.5 to 2.0 mm, the fracture strength of IPS e.max CAD group was significantly higher than that of Vita Enamic group. The results of SEM showed that the filler particles of IPS e.max CAD were smaller compared to that of Vita Enamic. Cone cracks were mainly found in the fracture surface of IPS e.max CAD, while radical cracks appeared in Vita Enamic. EDS showed the metal oxide and SiO2 in Vita Enmic was significantly higher than that in IPS e.max CAD. XRD showed that the primary crystal phase of IPS e.max CAD was lithium silicate, while Vita Enamic was amorphous. CONCLUSIONS: Both IPS e.max CAD and Vita Enamic can meet the standard of clinical application as the occlusal thickness reaches 1.5 mm. IPS e.max CAD showed better fracture resistance when the thickness was greater than 2.0 mm.

[Study on the effect of bone-cement interface with bone cement oscillator].

OBJECTIVE: To evaluate the effect on increasing bone cement-bone interface micro-gomphosis intensity with bone cement oscillator. METHODS: One hundred femoral bones of adult pig were randomly divided into 6 groups: oscillating group (A1) and control group (A2) of anti-tensile force, oscillating group (B1) and control group (B2) of anti-pressure (n = 20 in each group), oscillating group (C1) and control group (C2) of imaging (n = 10 in each group). Mechanics and CT test was performed, micro-gomphosis intensity of bone cement-bone interface between oscillating group and control group was compared. RESULTS: Mechanics and CT test showed bone cement-bone interface micro-gomphosis intensity in oscillating group was significantly stronger than control group (P < 0.01). CONCLUSION: Bone cement oscillator can significantly increase micro-gomphosis intensity of bone-cement interface, and reduce long-term aseptic loosening of artificial prostheses.

Genetic structure and demographic history should inform conservation: Chinese cobras currently treated as homogenous show population divergence.

An understanding of population structure and genetic diversity is crucial for wildlife conservation and for determining the integrity of wildlife populations. The vulnerable Chinese cobra (Naja atra) has a distribution from the mouth of the Yangtze River down to northern Vietnam and Laos, within which several large mountain ranges and water bodies may influence population structure. We combined 12 microsatellite loci and 1117 bp of the mitochondrial cytochrome b gene to explore genetic structure and demographic history in this species, using 269 individuals from various localities in Mainland China and Vietnam. High levels of genetic variation were identified for both mtDNA and microsatellites. mtDNA data revealed two main (Vietnam + southern China + southwestern China; eastern + southeastern China) and one minor (comprising only two individuals from the westernmost site) clades. Microsatellite data divided the eastern + southeastern China clade further into two genetic clusters, which include individuals from the eastern and southeastern regions, respectively. The Luoxiao and Nanling Mountains may be important barriers affecting the diversification of lineages. In the haplotype network of cytchrome b, many haplotypes were represented within a "star" cluster and this and other tests suggest recent expansion. However, microsatellite analyses did not yield strong evidence for a recent bottleneck for any population or genetic cluster. The three main clusters identified here should be considered as independent management units for conservation purposes. The release of Chinese cobras into the wild should cease unless their origin can be determined, and this will avoid problems arising from unnatural homogenization.

Immobilization of nanoscale Fe0 in and on PVA microspheres for nitrobenzene reduction.

In this study, nanoscale Fe(0) was immobilized in and on poly(vinyl alcohol) (PVA) microspheres by the inverse suspension crosslinked method. Two different sizes of Fe(0)/PVA microspheres were synthesized in the presence and absence of dispersant. The chelating action between Fe(2+) and PVA was identified by Fourier transform infrared and X-ray photoelectron spectroscopy. The morphology and distribution of the obtained Fe(0)/PVA microspheres were characterized by environmental scanning electron microscope, energy-dispersive X-ray spectrometry, and X-ray diffraction. Nanoscale Fe(0) particles were mostly dispersed over the surface of the microspheres. They were distributed more homogeneously on the surfaces of Fe(0)/PVA microspheres with diameter of 600-700 microm than those with diameter of 10-12 microm. The nitrobenzene (NB) reduction reactions followed pseudo-first-order kinetics. The normalized surface rate constants (k(SA)) values were determined to be 0.162 L h(-1)m(-2) for L-Fe(0)/PVA microspheres, 0.098 L h(-1)m(-2) for S-Fe(0)/PVA microspheres, and 0.023 L h(-1)m(-2) for nanoscale Fe(0) particles. Furthermore, with the analysis of the products by GC/MS, possible reductive pathways of NB by Fe(0)/PVA microspheres were suggested. The recovery rates of iron in microspheres were determined to be 81.17% for large Fe(0)/PVA and 60.31% for small Fe(0)/PVA.