Effects of Sjogren's syndrome and high sugar diet on oral microbiome in patients with rampant caries: a clinical study.

OBJECTIVE: The purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment. PATIENTS AND METHODS: Sixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren's syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray-Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal-Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P < 0.05). RESULTS: OTU principal component analysis revealed a significant difference between healthy individuals and those with RC-SS. In the saliva of patients with rampant caries, the relative abundance of Firmicutes increased significantly at the phylum level. Further, Streptocpccus, Veillonella, Prevotella, and Dialister increased, while Neisseria and Haemophilus decreased at the genus level. Veillonella increased in the plaque samples of patients with rampant caries. CONCLUSION: Both salivary and dental plaque composition were significantly different between healthy individuals and patients with rampant caries. This study provides a microbiological basis for exploring the etiology of rampant caries. CLINICAL RELEVANCE: This study provides basic information on the flora of the oral cavity in adults with rampant caries in China. These findings could serve as a reference for the treatment of this disease.

Polymer hydrogels with enhanced stability and heterogeneous Fenton activity in organic pollutant removal.

Polymer hydrogel-based materials have been shown to act as novel Fenton catalysts for water treatment, but the rational design of hydrogel-based catalysts with good stability has been a great challenge. To increase the stability and activity of polymer-based Fenton catalysts, uniform urchin-like α-Fe2O3 was grown in situ in a PVA carrier matrix here. PVA molecules promoted the growth of urchin-like α-Fe2O3, and then the PVA hydrogel acted as a barrier and carrier to reduce agglomeration. Through coordination by hydroxyl groups, PVA had good combination with Fe ions and α-Fe2O3. The formation of Fe-O-C bonds between iron oxides and polymers was reported for the first time, enhancing the material stability during catalysis. Under higher PVA concentrations, the resulting composite hydrogel could generate more ˙OH due to the increase in the number of active sites because of the hairy urchin-like structure. In tetracycline degradation through a heterogeneous Fenton reaction, the resulting material had good catalytic activity from pH 2 to pH 10 with low iron leaching, good reusability and remained at a level of nearly 90% after five consecutive cycles. Density functional theory calculations were used to further prove the mechanism of structural change of the iron oxides. The HOMO and LUMO energies of the iron oxides changed from 5.428 and 4.899 eV to 5.926 and 5.310 eV, indicating that the presence of PVA could influence the charge of the iron atom. The results provide new insights into the preparation of polymer hydrogel-based heterogeneous Fenton catalysts with enhanced stability for water treatment.

Dye removal by eco-friendly physically cross-linked double network polymer hydrogel beads and their functionalized composites.

Hydrogels have attracted large attention in wastewater treatment fields due to their low-cost and good interaction with pollutants, among which novel double network hydrogel is an outstanding class. To expand the application of double network hydrogel in water treatment, in this study, eco-friendly physically cross-linked double network polymer hydrogel beads (DAP) are prepared and studied in depth on the mechanism of Methylene Blue (MB) adsorption; and then the polymer hydrogels are further functionalized by inorganic materials. MB adsorption on DAP favors alkaline condition which is due to the increase of electrostatic attraction and adsorption site, and it reaches equilibrium within 10 hr, which is faster than that of the single network hydrogel beads (SAP). Through thermodynamics study, the process shows to be an exothermic and spontaneous process. The adsorption isotherms are well fitted by Langmuir model, with a maximum monolayer adsorption capacity of 1437.48 mg/g, which is larger than SAP (1255.75 mg/g). After being functionalized with common inorganic materials including activated carbon, Fe3O4 and graphene oxide (GO), the composites show to have larger pore sizes and have obvious increases in adsorption capacity especially the one contains GO. Then the composites contains Fe3O4 are used as heterogeneous Fenton catalyst which shows to have excellent performance in MB degradation. The results indicate the potential of polymer double network to be functionalized in environmental areas.

A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice.

Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is an autosomal dominant genetic disorder characterized by small palpebral fissures and other craniofacial malformations, often with (type I) but could also without (type II) premature ovarian failure. While mutations of the forkhead transcription factor FOXL2 are associated with and likely be responsible for many BPES cases, how FOXL2 affects craniofacial development remain to be understood. Through a large-scale piggyBac (PB) insertion mutagenesis, we have identified a mouse mutant carrying a PB insertion ∼160 kb upstream of the transcription start site (TSS) of Foxl2. The insertion reduces, but not eliminates, the expression of Foxl2. This mutant, but not its revertant, displays BPES-like conditions such as midface hypoplasia, eyelid abnormalities and female subfertility. Further analysis indicates that the mutation does not affect mandible, but causes premature fusion of the premaxilla-maxilla suture, smaller premaxilla and malformed maxilla during midface development. We further identified an evolutionarily conserved fragment near the insertion site and observed enhancer activity of this element in tissue culture cells. Analyses using DNase I hypersensitivity assay and chromosome conformation capture assay in developing maxillary and periocular tissues suggest that the DNA region near the insertion site likely interacts with Foxl2 TSS. Therefore, this mutant presents an excellent animal model for mechanistic study of BPES and regulation of Foxl2.

A Novel Ectodysplasin a Gene mutation of X-Linked Hypohidrotic Ectodermal Dysplasia.

Introduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings. Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay. Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent. Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.

Micro-macro SERS strategy for highly sensitive paper cartridge with trace-level molecular detection.

Surface-enhanced Raman Scattering (SERS) has become a powerful spectroscopic technology for highly sensitive detection. However, SERS is still limited in the lab because it either requires complicated preparation or is limited to specific compounds, causing poor applicability for practical applications. Herein, a micro-macro SERS strategy, synergizing polymer-assisted printed process with paper-tip enrichment process, is proposed to fabricate highly sensitive paper cartridges for sensitive practical applications. The polymer-assisted printed process finely aggregates nanoparticles with a discrete degree of 1.77, and SERS results are matched with theoretical enhancement, indicating small cluster-dominated hotspots at the micro-scale and thus 41-fold SERS increase compared to other aggregation methods. The paper-tip enrichment process moves molecules in a fluid into small tips filled with plasmonic clusters, and molecular localization at hotspots is achieved by the simulation and optimization of fluidic velocity at the macro-scale, generating a 39.5-fold SERS sensibility increase in comparison with other flow methods. A highly sensitive paper cartridge contains a paper-tip and a 3D-printed cartridge, which is simple, easy-to-operate, and costs around 2 US dollars. With a detection limit of 10 -12 M for probe molecules, the application of real samples and multiple analytes achieves single-molecule level sensitivity and reliable repeatability with a 30-min standardized procedure. The micro-macro SERS strategy demonstrates its potential in practical applications that require point-of-care detection.

Intrarenal delivery of bFGF-loaded liposome under guiding of ultrasound-targeted microbubble destruction prevent diabetic nephropathy through inhibition of inflammation.

Basic fibroblast growth factor (bFGF) has shown great therapeutic effects for diabetic nephropathy (DN). However, its clinical applications are limited due to its short half-life, low stability and poor penetration. Herein, a bFGF-loaded liposome (bFGF-lip) was constructed and combined with ultrasound-targeted microbubble destruction (UTMD) to overcome these drawbacks. bFGF-lip exhibited spherical morphology with a diameter of 171.1 ± 14.2 nm and a negative zeta potential of -5.15 ± 2.08 mV, exhibiting a sustained-release profile of bFGF. DN rat models were successfully induced by streptozotocin. After treatment with bFGF-lip + UTMD, the concentration of bFGF in kidney of DN rats was significantly enhanced in comparison with free bFGF treatment. Additionally, the morphology and the function of the kidneys were obviously recovered after bFGF-lip + UTMD treatment as shown by ultrasonography and histological analyse. The molecular mechanism was associated with the inhibition of renal inflammation. After treatment with bFGF-lip + UTMD, the activation of NF-κB was obviously reduced in the renal tissues, and downstream inflammatory mediators including TGF-ß1, MCP-1, IL-6 and IL-1ß were also down regulated. In addition, inflammation-induced cellular apoptosis of renal tubular cells was also significantly inhibited by detecting Bax, caspase-3 and Bcl-2. Therefore, bFGF-lip in combination with UTMD might be a potential strategy to reverse the progression of early DN.

Combination of coenzyme Q10-loaded liposomes with ultrasound targeted microbubbles destruction (UTMD) for early theranostics of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN. CoQ10-lip exhibited a good round morphology with a diameter of 183±1.7nm and a negative zeta potential of -25.3mV, which was capable of prolonging the release of the encapsulated CoQ10. The early DN rat models were induced by streptozotocin (STZ) and confirmed by contrast-enhanced ultrasound (CEUS) and 24-h urinary albumin. After the administration of CoQ10-lip combined with the UTMD technique to rats with early DN, the morphology and function of the kidney were evaluated by ultrasonography, histological and molecular analyses. The renal hemodynamics were significantly improved, moreover, 24-h urinary protein, and oxidative stress indexes were modulated after treatment with CoQ10-lip+UTMD indicating recovery of renal function. An elevated level of Nphs2 protein and reduced caspase 3 level indicated the preservation of podocytes and inhibition of cell apoptosis after CoQ10-lip+UTMD treatment. The molecular mechanism was associated with the upregulation of Bcl-2 and the downregulation of Bax. Moreover, the combination of CoQ10-lip and ultrasound microbubbles demonstrated a better protective effect on the damaged kidney than the other groups (free CoQ10 or CoQ10-lip+/- UTMD). Conclusively, CoQ10-lip in combination with ultrasound microbubbles might be a potential strategy to reverse the progress of early DN.

Measurement and analysis of associated mimic muscle movements.

OBJECTIVE: To measure movements of markers over the primary site and associated mimic muscles in certain facial expressions, for evaluating facial paresis and synkinesis. METHODS: Participants included 22 normal subjects aged 45-66 years. Maximum shift (Smax) and velocity (Vmax) were measured using a custom-designed 3-D dynamic quantitative analysis system of facial motion (3-D ASFM) based on motion capture technology. Measures were taken from peri-oral muscles during forceful brow raising and tight eye closure, and from muscles around the eye during grinning, right/left/bilateral mouth corner raising and smiling. RESULTS: 1) During forceful brow raising, Smax was 3.65-4.46 mm for markers over perioral muscles, with the marker over the nasolabial fold showing a Vmax greater than others (60.60 mm/s on left and 62.70 mm/s on right). 2) In tight eye closure, Smax of perioral muscle markers was 1.58-1.92 mm, with Vmax being 11.40-14.76 mm/s. 3) In grinning, the largest eye muscle marker Smax was seen at the lower lid (3.93 mm on left and 4.15 mm on right) and the smallest at the inner canthus (1.59 mm on left and 1.53 mm on right), with the largest Vmax seen at the upper lid and smallest also at the inner canthus (11.71 mm/s on left and 11.09 mm/s on right). 4) In smiling, the largest non-oral Smax and Vmax were seen at the upper lid (3.05 mm and 36.14 mm/s on left and 2.53 mm and 28.90 mm/s on right) and the smallest also at the inner canthus (0.69 mm and 7.22 mm/s on left and 0.77 mm and 7.80 mm/s on right). 5) In right mouth corner raising, Smax and Vmax at lateral and medial canthus and at lower lid were greater on right than left, while those at upper lid and brow were slightly greater on left than right. 6) In left mouth corner raising, Smax and Vmax at lateral canthus and upper and lower lids were greater on left than right. CONCLUSIONS: There are no absolute immobile points on the face when making facial expressions. In addition to the primary movement site, there are associated movements at other points on the face with consistent Smax and Vmax. In assessing facial paresis and synkinesis, physiological associated facial movements should be taken into consideration.

Adsorption of water-soluble dyes onto modified resin.

Adsorption behavior of five kinds of water-soluble dyes onto functionalized resin NKY has been dynamically and thermodynamically investigated. The results showed that the adsorption rates of dye K-GN, K-2BP, KN-R, AAB and 2G are all controlled by liquid film diffusion and particle diffusion. Equilibrium adsorption data can be well described by three-parameter equation. The first layer adsorption is the physical enhanced by chemical effect but multilayer adsorption is typically physical adsorption. Standard free energy change DeltaG(0) and standard entropy change DeltaS(0) indicate the adsorption of the dyes onto NKY can occur spontaneously.

B-lymphocyte depletion ameliorates Sjögren's syndrome in Id3 knockout mice.

Sjögren's syndrome is an autoimmune disease in which immune cells chronically attack the lachrymal and salivary glands. The Id3 knockout mouse is a newly established animal model for primary Sjögren's syndrome. To address the role of B cells in Sjögren's syndrome and autoimmune disease, we studied the effect of CD20 monoclonal antibody treatment on the disease in Id3 knockout mice. Antibody treatment at 2-month intervals led to efficient and sustained B-cell depletion in Id3 knockout mice. A significant improvement of histopathology was observed accompanied by the recovery of saliva secretory function after CD20 antibody treatment. We further show that serum immunoglobulin G3, which is abnormally high in untreated Id3 knockout mice, was reduced after CD20 antibody treatment. This study establishes a new animal model for immunotherapy of Sjögren's symptoms and suggests a possible link between immunoglobulin G3 and disease pathology in Id3 knockout mice.

[Effects of silicate on the community structure of phytoplankton in enclosures].

Controlling the concentrations of silicate, enclosure experiments were conducted in Xinkai Lake to investigate the influence of Si concentration on the growth and succession of phytoplankton communities in a eutrophic freshwater. The results show that with the addition of silicate, the biomass of diatoms increased and the ratio of diatom species to the total significantly increased from 10.2% to 22.1% . While the species percent of Cyanobacteria and Chlorophyta decreased to 61.5%, as compared with 76.8% in control. Several diatom species, such as Synedra ulna, Nitzschia denticula, Nitzschia acicularis, Gomphonema constrictum var. capitata, Gomphonema olivaceum, which were not found in control, were observed in the silicate-enriched treatments. The Shannon indices of 2.17 +/- 0.40 and 2.12 +/- 0.21 were obtained from the medium-Si (atomic ratio N:Si:P = 16:8:1) and high-Si ( N:Si:P = 16:16:1) treatments, which were higher than that of the control enclosure (1.89 +/- 0.55, without silicate addition). At the late phase of the experiments, algal blooms mainly composed of Microcystis aeruginosa appeared in control but not in the silicate-enriched enclosures. The enrichment of silicate can promote the growth of diatoms and the other algal species and change the dominance of few Cyanobacteria and Chlorophyte species. Therefore, it can elevate the algal biodiversity of an aquatic ecosystem and weaken the cyanobacterial blooms to a certain degree.

A T cell intrinsic role of Id3 in a mouse model for primary Sjogren's syndrome.

Sjogren's syndrome is an autoimmune disease with clinical hallmarks of keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth). The genetic basis of this autoimmune disease is poorly understood. Id3 is an immediate early-response gene in growth regulation and is involved in TCR-mediated T cell selection during T cell development. Here, we show that Id3-deficient mice develop many disease symptoms found in primary Sjogren's syndrome patients including dry eyes and mouth, lymphocyte infiltration in lachrymal and salivary glands, and development of anti-Ro and anti-La antibodies. Adoptive transfer experiment indicated a T cell intrinsic role for Id3 in the development of Sjogren's symptoms. Furthermore, genetic ablation of T cells or neonatal 3 day thymectomy in Id3-deficient mice showed a rescue of disease symptoms, suggesting a thymic origin of autoimmune T cells. Thus, this study establishes a critical connection between Id3-mediated T cell development and autoimmune diseases.