Low intensity ultrasound-mediated drug-loaded nanoparticles intravaginal drug delivery: an effective synergistic therapy scheme for treatment of vulvovaginal candidiasis.

PURPOSE: Vulvovaginal candidiasis (VVC) is a mucosal infection of the female lower genital tract for which treatment using conventional antifungal drugs shows limited effectiveness. Herein, amphotericin B-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (AmB-NPs) were fabricated and combined with low intensity ultrasound (US) to mediate AmB-NPs intravaginal drug delivery to achieve productive synergistic antifungal activity in a rabbit model of VVC. METHODS: Polymeric AmB-NPs were fabricated by a double emulsion method and the physical characteristics and biosafety of nanoparticles were analyzed. The distribution and tissue permeability of nanoparticles after intravaginal ultrasound irradiation (1.0 MHz, 1.0 W/cm2, 5 min, 50% duty ratio) were observed in the vagina. The synergistic therapeutic activity of US-mediated AmB-NPs treatment was evaluated using an experimental rabbit model of VVC. Vaginal C. albicans colony counts, the pathological structure of the vagina epithelium, and Th1/Th2/Th17-type cytokine and oxidative stress levels were analyzed to investigate the therapeutic effect in vivo. RESULTS: The prepared AmB-NPs showed an obvious shell and core structure with uniform size and good dispersion and displayed high biosafety and US-sensitive slow drug release. Ultrasound significantly enhanced nanoparticle transport through the mucus and promoted permeability in the vaginal tissue. US-mediated AmB-NPs treatment effectively increased drug sensitivity, even in the presence of the vaginal mucus barrier in vitro. On the seventh day after treatment in vivo, the combination treatment of AmB-NPs and US significantly reduced the fungal load in the vagina, achieving over 95% clearance rates, and also improved the pathological epithelium structural damage and glycogen secretion function. The expression of Th1 (IFN-γ, IL-2) and Th17 (IL-17) cytokines were significantly increased and Th2 (IL-6, IL-10) cytokines significantly decreased in the US + AmB-NP group. Furthermore, US-mediated AmB-NPs treatment effectively increased C. albicans intracellular reactive oxygen species (ROS) levels and promoted vaginal oxidation and antioxidants to normal levels. CONCLUSION: US-mediated drug-loaded nanoparticles with intravaginal drug delivery exhibited a productive synergistic antifungal effect, which may provide a new non-invasive, safe, and effective therapy for acute or recurrent fungal vaginitis.

Overexpression of PnMYB2 from Panax notoginseng induces cellulose and lignin biosynthesis during cell wall formation.

MAIN CONCLUSION: Panax notoginseng PnMYB2 is a transcriptional activator of primary and secondary cell wall formation by promoting the PCW-specific gene CesA3 and key lignin biosynthetic gene CCoAOMT1, respectively. R2R3-MYB transcription factors play important roles in regulation secondary cell wall (SCW) formation. However, there are few reports on the functions of MYB transcription factors which involved in both primary cell wall (PCW) and SCW formation. Here, we isolated an R2R3-MYB transcription factor, PnMYB2, from Panax notoginseng roots which are widely used in Chinese traditional medicines and contain abundant cellulose and lignin. The expression pattern of PnMYB2 was similar to the accumulation pattern of cellulose and lignin contents in different organs. PnMYB2 localized in the nucleus and may function as a transcriptional activator. Overexpression of PnMYB2 in Arabidopsis thaliana enhanced cellulose and lignin biosynthesis, and remarkably increased thickness of PCW and SCW in the stem of transgenic plants compared with wild-type plants. The expression levels of genes associated with PCW-specific cellulose synthase (CesA) genes and key SCW-specific lignin biosynthetic genes were significantly increased in PnMYB2-overexpressing plants compared to the wild type plants. Furthermore, yeast one-hybrid, dual-luciferase reporter assays and electrophoretic mobility shift assays (EMSA) results verified that PnMYB2 could bind and activate the promoters of AtCesA3 and PnCesA3, which are the PCW-specific cellulose biosynthetic genes, and AtCCoAOMT1 and PnCCoAOMT1, which are the key lignin biosynthetic genes. These results demonstrated the central role of PnMYB2 in PCW-specific cellulose formation and SCW-specific lignin biosynthesis.

A Novel Magnetotactic Alphaproteobacterium Producing Intracellular Magnetite and Calcium-Bearing Minerals.

Magnetotactic bacteria (MTB) are prokaryotes that form intracellular magnetite (Fe3O4) or greigite (Fe3S4) nanocrystals with tailored sizes, often in chain configurations. Such magnetic particles are each surrounded by a lipid bilayer membrane, called a magnetosome, and provide a model system for studying the formation and function of specialized internal structures in prokaryotes. Using fluorescence-coupled scanning electron microscopy, we identified a novel magnetotactic spirillum, XQGS-1, from freshwater Xingqinggong Lake, Xi'an City, Shaanxi Province, China. Phylogenetic analyses based on 16S rRNA gene sequences indicate that strain XQGS-1 represents a novel genus of the Alphaproteobacteria class in the Proteobacteria phylum. Transmission electron microscopy analyses reveal that strain XQGS-1 forms on average 17 ± 3 magnetite magnetosome particles with an ideal truncated octahedral morphology, with an average length and width of 88.3 ± 11.7 nm and 83.3 ± 11.0 nm, respectively. They are tightly organized into a single chain along the cell long axis close to the concave side of the cell. Intrachain magnetic interactions likely result in these large equidimensional magnetite crystals behaving as magnetically stable single-domain particles that enable bacterial magnetotaxis. Combined structural and chemical analyses demonstrate that XQGS-1 cells also biomineralize intracellular amorphous calcium phosphate (2 to 3 granules per cell; 90.5- ± 19.3-nm average size) and weakly crystalline calcium carbonate (2 to 3 granules per cell; 100.4- ± 21.4-nm average size) in addition to magnetite. Our results expand the taxonomic diversity of MTB and provide evidence for intracellular calcium phosphate biomineralization in MTB. IMPORTANCE Biomineralization is a widespread process in eukaryotes that form shells, teeth, or bones. It also occurs commonly in prokaryotes, resulting in more than 60 known minerals formed by different bacteria under wide-ranging conditions. Among them, magnetotactic bacteria (MTB) are remarkable because they might represent the earliest organisms that biomineralize intracellular magnetic iron minerals (i.e., magnetite [Fe3O4] or greigite [Fe3S4]). Here, we report a novel magnetotactic spirillum (XQGS-1) that is phylogenetically affiliated with the Alphaproteobacteria class. In addition to magnetite crystals, XQGS-1 cells form intracellular submicrometer calcium carbonate and calcium phosphate granules. This finding supports the view that MTB are also an important microbial group for intracellular calcium carbonate and calcium phosphate biomineralization.

Three Cambrian fossils assembled into an extinct body plan of cnidarian affinity.

The early Cambrian problematica Xianguangia sinica, Chengjiangopenna wangii, and Galeaplumosus abilus from the Chengjiang biota (Yunnan, China) have caused much controversy in the past and their phylogenetic placements remain unresolved. Here we show, based on exceptionally preserved material (85 new specimens plus type material), that specimens previously assigned to these three species are in fact parts of the same organism and propose that C. wangii and G. abilus are junior synonyms of X. sinica Our reconstruction of the complete animal reveals an extinct body plan that combines the characteristics of the three described species and is distinct from all known fossil and living taxa. This animal resembled a cnidarian polyp in overall morphology and having a gastric cavity partitioned by septum-like structures. However, it possessed an additional body cavity within its holdfast, an anchoring pit on the basal disk, and feather-like tentacles with densely ciliated pinnules arranged in an alternating pattern, indicating that it was a suspension feeder rather than a predatory actiniarian. Phylogenetic analyses using Bayesian inference and maximum parsimony suggest that X. sinica is a stem-group cnidarian. This relationship implies that the last common ancestor of X. sinica and crown cnidarians was probably a benthic, polypoid animal with a partitioned gastric cavity and a single mouth/anus opening. This extinct body plan suggests that feeding strategies of stem cnidarians may have been drastically different from that of their crown relatives, which are almost exclusively predators, and reveals that the morphological disparity of total-group Cnidaria is greater than previously assumed.

The pressure in the temporomandibular joint in the patients with maxillofacial deformities.

BACKGROUND: Temporomandibular disorder (TMD) symptoms were found to be common in the patients with maxillofacial deformities. The mandibular structure was in relation with the stress within temporomandibular joint (TMJ). However, the current studies on the TMJ stresses in the patients with different maxillofacial deformities are not comprehensive enough. PURPOSE: The aim of this study was to investigate the compression and morphology of the TMJ in the patients with different maxillofacial deformities under central occlusion. METHODS: 24 patients and 10 asymptomatic individuals were included in this study and divided into patient groups and control group. The 3D models were reconstructed. Muscle forces and boundary conditions corresponding to the central occlusion were applied. Nine morphological parameters of mandible were evaluated. RESULTS: The minimum principal stresses in the articular disc and condyle were significantly greater than those of the control group (P<0.05). For the articular disc, the compression on the non-deviation side was greater than those on the deviation side in patients with asymmetrical mandibles. There was difference between both sides in the mandibular prognathism and retrusion groups. The joint space of patients was significantly lower than that of the control group (P<0.05). CONCLUSIONS: Maxillofacial deformities might change the condylar position within the articular fossa, which decreased the joint space and increased the compression within TMJ. The patients with asymmetry mandible suffered greater pressure within TMJ on the non-deviation side. The bilaterally over-developed and under-developed mandible in patients might also increase the compression within TMJ.

Clinical Analysis and CT 3D-Mediated Precise Internal Fixation in Maxillofacial Fracture.

BACKGROUND/PURPOSE: To retrospectively analyze the epidemiological features, clinical diagnosis, and treatment of 610 patients with maxillofacial fractures, while providing a reference for the prevention and optimized treatment of maxillofacial fractures. METHODS: Data of patients with maxillofacial fractures who were treated and followed up at the Second People's Hospital of Kashi Prefecture from June 2012 to April 2018 were summarized. The epidemiological features, clinical manifestations, fracture sites, treatment methods, and results were analyzed. RESULTS: The highest incidence was in the age range of 20 to 49 years. The main cause of fracture was traffic injury. Mandibular fractures accounted for 37.77%, zygoma and zygomatic arch fractures for 37.00%, and maxillary fractures for 21.19%. Atypical zygomatic arch fractures were more common in the maxilla, followed by Le Fort I and II fractures. Closed fractures accounted for 85.97%. Many (73.39%) patients were treated with computed tomography 3-dimensional (3D)-mediated precision modified incision internal fixation with satisfactory results. CONCLUSIONS: There is a high incidence of maxillofacial fractures among young men, especially in summer, with the most common injuries being traffic-related injuries. The most common site is the mandible, followed by the zygomatic arch, zygomatic complex, and maxilla. Computed tomography 3D-mediated precision modified incision internal fixation can achieve satisfactory results.

Solitary extranodal Rosai-Dorfman disease of the mandible: an exceedingly rare presentation.

Sinus histiocytosis with massive lymphadenopathy, generally known by the name of Rosai-Dorfman disease is a rare benign condition principally affecting cervical lymph nodes. Concurrent extra-nodal disease frequently occurs, however, solitary extra-nodal disease involving the mandible is exceedingly rare with less than five reported cases in the English literature. We describe a case of primary involvement of the mandible in a 27-year-old female, and discuss the differential diagnosis of this disease with other histiocytic lesions.

Solitary extranodal Rosai-Dorfman disease of the mandible: an exceedingly rare presentation

Sinus histiocytosis with massive lymphadenopathy, generally known by the name of Rosai-Dorfman disease is a rare benign condition principally affecting cervical lymph nodes. Concurrent extra-nodal disease frequently occurs, however, solitary extra-nodal disease involving the mandible is exceedingly rare with less than five reported cases in the English literature. We describe a case of primary involvement of the mandible in a 27-year-old female, and discuss the differential diagnosis of this disease with other histiocytic lesions.

A sclerite-bearing stem group entoproct from the early Cambrian and its implications.

The Lophotrochozoa includes disparate tentacle-bearing sessile protostome animals, which apparently appeared in the Cambrian explosion, but lack an uncontested fossil record. Here we describe abundant well preserved material of Cotyledion tylodes Luo et Hu, 1999, from the Cambrian (Series 2) Chengjiang deposits, reinterpreted here as a stem-group entoproct. The entoproct affinity is supported by the sessile body plan and interior soft anatomy. The body consists of an upper calyx and a lower elongate stalk with a distal holdfast. The soft anatomy includes a U-shaped gut with a mouth and aboral anus ringed by retractable marginal tentacles. Cotyledion differs from extant entoprocts in being larger, and having the calyx and the stalk covered by numerous loosely-spaced external sclerites. The description of entoprocts from the Chengjiang biota traces the ancestry of yet another lophotrochozoan phylum back to the Cambrian radiation, and has important implications for the earliest evolution of lophotrochozoans.