Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

Accuracy assessment of implant placement with versus without a CAD/CAM surgical guide by novices versus specialists via the digital registration method: an in vitro randomized crossover study.

BACKGROUND: Many studies demonstrated that surgical guides might reduce discrepancies compared with freehand implant placement. This randomized crossover study aimed to assess the effects of approaches, practitioners' experience and learning sequences on the accuracy of single tooth implantation via digital registration method. No similar study was found. METHODS: This in vitro randomized crossover study enrolled 60 novice students (Group S) and 10 experienced instructors (Group I). Sixty students were randomly and evenly assigned to two groups (Group SA and SB). In Group SA, 30 students first performed single molar implant on a simulation model freehand (Group SAFH), and then with a CAD/CAM surgical guide (Group SASG). In Group SB, another 30 students first performed guided (Group SBSG) and then freehand (Group SBFH). Ten instructors were also divided into Group IAFH/IASG (n = 5) and IBSG/IBFH (n = 5) following the same rules. The accuracy of implant placement was assessed by the coronal and apical distance (mm) and angular (°) deviations using the digital registration method. T tests and nonparametric tests were used to compare the results among different groups of approaches, experience and sequences. RESULTS: For students, the coronal and apical distance and the angular deviations were significantly lower in surgical guide group than freehand group in total and in learning freehand first subgroup, but for learning surgical guide first subgroup the apical distance deviation showed no significant difference between two approaches. For students, the angular deviation of freehand group was significantly lower in learning surgical guide first group than learning freehand first group. For instructors, the coronal and apical distance and angular deviations showed no significant difference between two approaches and two sequences. For freehand approach, the coronal and apical distance and the angular deviations were significantly higher in student group than instructor group, while not significantly different between two groups for surgical guide approach. CONCLUSIONS: For novices, using a surgical guide for the first implant placement may reduce the potential deviations compared with freehand surgery, and may reach a comparable accuracy with that of specialists. For simple single molar implantation, the surgical guide may not be significantly helpful for experienced specialists.

[Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells].

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

Digital versus radiographic accuracy evaluation of guided implant surgery: an in vitro study.

BACKGROUND: Cone-beam computed tomography (CBCT) is the most widely used method for postsurgical evaluation of the accuracy of guided implant surgery. However, the disadvantages of CBCT include radiation exposure, artifacts caused by metal implants, and high cost. Few studies have introduced a digital registration method to replace CBCT for evaluating the accuracy of guided surgery. The purpose of this study was to compare digital registration to conventional CBCT in terms of the capacity to evaluate the implant positioning accuracy of guided surgery. MATERIALS AND METHODS: This in vitro study included 40 acrylic resin models with posterior single mandibular tooth loss. Guided surgery software was used to determine the optimal implant position; 40 tooth-supported fully guided drilling templates were designed and milled accordingly. After the guided surgery, the accuracies of the surgical templates were evaluated by conventional CBCT and digital registration. For evaluation by conventional CBCT, postsurgical CBCT scans of the resin models were performed. The CBCT data were reconstructed and superimposed on the implant planning data. For digital registration, we constructed a virtual registration unit that consisted of an implant replica and a scan body. Next, we obtained postsurgical optical scans of resin models with the scan body. The postsurgical implant position was identified by superimposition of the registration unit and optical scan data. The implant planning data and postsurgical implant position data were superimposed; deviations were reported in terms of distance for implant entry/apex point and in terms of angle for the implant axis. Interclass correlation coefficients (ICCs) and Bland-Altman plots were used to analyze the agreement between the two evaluation methods. RESULTS: The ICCs between the two methods were 0.986, 0.993, and 0.968 for the entry point, apex point, and angle, respectively; all were significantly greater than 0.75 (p < 0.001). Bland-Altman plots showed that the 95% limits of agreement of the differences were - 0.144 to + 0.081 mm, - 0.135 to + 0.147 mm, and - 0.451° to + 0.729° for the entry point, apex point, and angle, respectively; all values were within the maximum tolerated difference. CONCLUSION: Conventional CBCT and digital registration showed good agreement in terms of evaluating the accuracy of implant positioning using tooth-supported surgical templates.

Secular trends in severe periodontitis incidence, prevalence and disability-adjusted life years in five Asian countries: A comparative study from 1990 to 2017.

AIMS: To investigate secular trends in severe periodontitis incidence, prevalence and disability-adjusted life year (DALY) rates in China, India, Japan, South Korea and Thailand from 1990 to 2017. MATERIALS AND METHODS: Data were obtained from the "Global Burden of Disease Study" 2017. The annual percentage change and average annual percentage change were calculated using Joinpoint regression analysis. The independent age, period and cohort effects were estimated by age-period-cohort analysis. RESULTS: From 1990 to 2017, the overall age-standardized incidence, prevalence and DALY rates increased in China, Japan and India, while decreasing in South Korea and Thailand. The highest incidence, prevalence and DALY rates were in India. By APC analysis, the age effect presented increase in 20-59 years in China, Japan and South Korea, 20-54 years in India and 20-64 years in Thailand; the period effect showed progressive increases in five countries, with the most significant increase shown in China; the cohort effect showed monotonic decreases with birth cohort in five countries. CONCLUSIONS: Severe periodontitis poses a serious burden in Asian countries, especially China and India. We suggest raising people's awareness of periodontal health and providing professional interventions in these countries, especially for high-risk groups, such as younger people aged ≤65 years.

Comparative transcriptome analysis indicates that a core transcriptional network mediates isonuclear alloplasmic male sterility in wheat (Triticum aestivum L.).

BACKGROUND: Cytoplasmic male sterility (CMS) plays a crucial role in the utilization of heterosis and various types of CMS often have different abortion mechanisms. Therefore, it is important to understand the molecular mechanisms related to anther abortion in wheat, which remain unclear at present. RESULTS: In this study, five isonuclear alloplasmic male sterile lines (IAMSLs) and their maintainer were investigated. Cytological analysis indicated that the abortion type was identical in IAMSLs, typical and stainable abortion, and the key abortive period was in the binucleate stage. Most of the 1,281 core shared differentially expressed genes identified by transcriptome sequencing compared with the maintainer in the vital abortive stage were involved in the metabolism of sugars, oxidative phosphorylation, phenylpropane biosynthesis, and phosphatidylinositol signaling, and they were downregulated in the IAMSLs. Key candidate genes encoding chalcone--flavonone isomerase, pectinesterase, and UDP-glucose pyrophosphorylase were screened and identified. Moreover, further verification elucidated that due to the impact of downregulated genes in these pathways, the male sterile anthers were deficient in sugar and energy, with excessive accumulations of ROS, blocked sporopollenin synthesis, and abnormal tapetum degradation. CONCLUSIONS: Through comparative transcriptome analysis, an intriguing core transcriptome-mediated male-sterility network was proposed and constructed for wheat and inferred that the downregulation of genes in important pathways may ultimately stunt the formation of the pollen outer wall in IAMSLs. These findings provide insights for predicting the functions of the candidate genes, and the comprehensive analysis of our results was helpful for studying the abortive interaction mechanism in CMS wheat.

Transcription Factor Atf1 Regulates Expression of Cellulase and Xylanase Genes during Solid-State Fermentation of Ascomycetes.

Transcriptional regulation of cellulolytic and xylolytic genes in ascomycete fungi is controlled by specific carbon sources in different external environments. Here, comparative transcriptomic analyses of Penicillium oxalicum grown on wheat bran (WB), WB plus rice straw (WR), or WB plus Avicel (WA) as the sole carbon source under solid-state fermentation (SSF) revealed that most of the differentially expressed genes (DEGs) were involved in metabolism, specifically, carbohydrate metabolism. Of the DEGs, the basic core carbohydrate-active enzyme-encoding genes which responded to the plant biomass resources were identified in P. oxalicum, and their transcriptional levels changed to various extents depending on the different carbon sources. Moreover, this study found that three deletion mutants of genes encoding putative transcription factors showed significant alterations in filter paper cellulase production compared with that of a parental P. oxalicum strain with a deletion of Ku70 (ΔPoxKu70 strain) when grown on WR under SSF. Importantly, the ΔPoxAtf1 mutant (with a deletion of P. oxalicumAtf1, also called POX03016) displayed 46.1 to 183.2% more cellulase and xylanase production than a ΔPoxKu70 mutant after 2 days of growth on WR. RNA sequencing and quantitative reverse transcription-PCR revealed that PoxAtf1 dynamically regulated the expression of major cellulase and xylanase genes under SSF. PoxAtf1 bound to the promoter regions of the key cellulase and xylanase genes in vitro This study provides novel insights into the regulatory mechanism of fungal cellulase and xylanase gene expression under SSF.IMPORTANCE The transition to a more environmentally friendly economy encourages studies involving the high-value-added utilization of lignocellulosic biomass. Solid-state fermentation (SSF), that simulates the natural habitat of soil microorganisms, is used for a variety of applications such as biomass biorefinery. Prior to the current study, our understanding of genome-wide gene expression and of the regulation of gene expression of lignocellulose-degrading enzymes in ascomycete fungi during SSF was limited. Here, we employed RNA sequencing and genetic analyses to investigate transcriptomes of Penicillium oxalicum strain EU2101 cultured on medium containing different carbon sources and to identify and characterize transcription factors for regulating the expression of cellulase and xylanase genes during SSF. The results generated will provide novel insights into genetic engineering of filamentous fungi to further increase enzyme production.

Design and evaluation of glomerulus mesangium-targeted PEG-PLGA nanoparticles loaded with dexamethasone acetate.

Mesangial proliferative glomerulonephritis (MsPGN), one of the most common glomerulonephritis pathological types, often leads to end-stage renal disease over a prolonged period. But the current treatment of MsPGN is non-specific and causes serious side effects, thus novel therapeutics and targeting strategies are urgently demanded. By combining the advantages of PEG-PLGA nanoparticles and the size selection mechanism of renal glomerulus, we designed and developed a novel PEG-PLGA nanoparticle delivery system capable of delivering dexamethasone acetate (A-DEX) into glomerular mesangium. We determined that 90 nm was the optimum size to encapsulate A-DEX for glomerular mesangium targeting based on the size-selection mechanism of glomerulus. After intravenous administration in rats, 90 nm DiD-loaded NPs were found to accumulate to a greater extent in the kidney and kidney cortex compared with the free DiD solution. The 90 nm A-DEX NPs are also more stable at room temperature and showed a sustained release pattern. In rat glomerular mesangial cells (HBZY-1) in vitro, we found that the uptake of 90 nm A-DEX NPs was both temperature-dependent and energe-dependent, and they were mostly engulfed via clathrin-dependent endocytosis pathways. In summary, we have successfully developed a glomerular mesangium-targeted PEG-PLGA NPs, which is potential for the treatment of MsPGN.

Fully automated searching for the optimal VMAT jaw settings based on Eclipse Scripting Application Programming Interface (ESAPI) and RapidPlan knowledge-based planning.

PURPOSE: Eclipse treatment planning system has not been able to optimize the jaw positions for Volumetric Modulated Arc Therapy (VMAT). The arbitrary and planner-dependent jaw placements define the maximum field size within which multi-leaf-collimator (MLC) sequences can be optimized to modulate the beam. Considering the mechanical constraints of MLC transitional speed and range, suboptimal X jaw settings may impede the optimization or undermine the deliverability. This work searches optimal VMAT jaw settings automatically based on Eclipse Scripting Application Programming Interface (ESAPI) and RapidPlan knowledge-based planning. METHODS AND MATERIALS: Using an ESAPI script, the X jaws of rectal VMAT plans were initially set to conform the planning-target-volume (PTV), and were gradually extended toward the isocenter (PTV center) in 5-7 mm increments. Using these jaw pairs, 592 plans were automatically created for 10 patients and quantitatively evaluated using a comprehensive scoring function. A published RapidPlan model was evoked by ESAPI to generate patient-specific optimization objectives without manual intervention. All candidate plans were first stored as text files to save storage space, and only the best, worst, and conformal plans were consequently recreated for comparison. RESULTS: Although RapidPlan estimates dose-volume histogram (DVH) based on individual anatomy, the geometry-based expected dose (GED) algorithm does not recognize different jaw settings but uses PTV-conformal jaws as default; hence, identical DVHs were observed regardless of planner-defined jaws. Therefore, ESAPI finalized dose-volume calculation and eliminated the plans with unacceptable hotspots before comparison. The plan quality varied dramatically with different jaw settings. Trade-offs among different organs-at-risk (OARs) were collectively considered by the proposed scoring method, which identified the best and worst plans correctly. The plans using conformal jaws were neither the best nor the worst of all candidates. CONCLUSIONS: VMAT plans using optimal jaw locations can be created automatically using ESAPI and RapidPlan. Conformal jaws are not the optimal choice.

[Tissue distribution of TPGS modified artesunate liposome and its metabolites in rats].

Artesunate, which is a widely used anti-malaria medicine, can be made into liposome to overcome its poor bioactivity. Its tissue distribution in rats may change with different dosage forms, which therefore shall be studied after ARS-TPGS-Lipo was injected. Based on this experiment, ARS-TPGS-Lipo and ARS-Lipo were prepared by thin-film hydration method. LC-MS/MS method was used to simultaneously determine ARS and DHA in rat tissues at different time points. The results showed that this method was suitable for the content analysis of ARS and DHA in biological samples. The distribution of ARS and DHA in ARS-TPGS-Lipo, ARS-Lipo and ARS groups were quite different. The content of ARS-TPGS-Lipo in liver was the highest, with significant differences.ARS and DHA contents in ARS group eliminated rapidly. ARS and DHA contents in ARS-Lipo group were higher in liver and spleen, while those in ARS-TPGS-Lipo group significantly increased only in liver (P<0.05).

Polyvinylidene Fluoride Micropore Membranes as Solid-Phase Extraction Disk for Preconcentration of Nanoparticulate Silver in Environmental Waters.

Efficient separation and preconcentration of trace nanoparticulate silver (NAg) from large-volume environmental waters is a prerequisite for reliable analysis and therefore understanding the environmental processes of silver nanoparticles (AgNPs). Herein, we report the novel use of polyvinylidene fluoride (PVDF) filter membrane for disk-based solid phase extraction (SPE) of NAg in 1 L of water samples with the disk-based SPE system, which consists of a syringe pump and a syringe filter holder to embed the filter membrane. While the PVDF membrane can selectively adsorb NAg in the presence of Ag+, aqueous solution of 2% (m/v) FL-70 is found to efficiently elute NAg. Analysis of NAg is performed following optimization of filter membrane and elution conditions with an enrichment factor of 1000. Additionally, transmission electron microscopy (TEM), UV-vis spectroscopy, and size-exclusion chromatography coupled with ICP-MS (SEC-ICP-MS) analysis showed that the extraction gives rise to no change in NAg size or shape, making this method attractive for practical applications. Furthermore, feasibility of the protocol is verified by applying it to extract NAg in four real waters with recoveries of 62.2-80.2% at 0.056-0.58 µg/L spiked levels. This work will facilitate robust studies of trace NAg transformation and their hazard assessments in the environment.

Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo.

Scopoletin is an active coumarin possessing a variety of pharmacological activities, including anti-hyperuricemic effect, but with poor solubility. To improve its oral bioavailability, we attempted to encapsulate scopoletin into Soluplus micelles (Soluplus-based scopoletin micelles, Sco-Ms) and evaluated the hypouricemic action of Sco-Ms. Sco-Ms were prepared using a thin-film hydration method. Sco-Ms displayed near spherical shapes with an average size of 59.4±2.4 nm (PDI=0.08±0.02). The encapsulation efficiency of scopoletin was 87.3%±1.5% with a loading capacity of 5.5%±0.1%. Sco-Ms were further characterized using transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared techniques and scanning electron microscopy. After oral administration in rats, Sco-Ms exhibited significantly improved absorption in each intestinal segment compared to free scopoletin, with the duodenum and jejunum being the main absorption regions. In rats administered Sco-Ms (at an equivalent dose of free scopoletin of 100 mg/kg, po), the AUC0-∞ and Cmax of Sco-Ms were 4.38- and 8.43-fold, respectively, as large as those obtained following administration of free scopoletin. After oral administration in rats, Sco-Ms did not alter the tissue distributions of scopoletin, but significantly increased the scopoletin levels in the liver. In potassium oxonate-induced hyperuricemic mice, oral administration of Sco-Ms (at an equivalent dose of free scopoletin of 300 mg/kg) reduced the serum uric acid concentration to the normal level. The results suggest that Soluplus-based micelle system greatly improves the bioavailability of poorly water-soluble drugs, such as scopoletin, and represents a promising strategy for their oral delivery.

A biomimetic collagen/heparin multi-layered porous hydroxyapatite orbital implant for in vivo vascularization studies on the chicken chorioallantoic membrane.

BACKGROUND: The vascularization of an orbital implant is a key issue for reducing complications, such as exposure and infection. METHODS: Here, we developed a facile layer-by-layer assembly approach to modify porous hydroxyapatite (pHA) orbital implants with five collagen (COL)/heparin (HEP) multilayers. RESULTS: SEM characterization showed that the average pore size of the pHA/(COL/HEP)5 scaffold was 316.8 ± 77.1 µm. After being coated with five COL/HEP multilayers, the mechanical strength was improved compared with that of the pHA scaffolds. The in vitro assay displayed that the pHA scaffolds covered with COL/HEP multilayers resulted in a larger number of human umbilical vein endothelial cells after being cultured for 14 days. The macroscopic evaluation and semi-quantitative vascular density analysis of the chicken chorioallantoic membrane assay showed that the pHA/(COL/HEP)5 scaffolds resulted in more intense angiogenesis than the pHA scaffolds. CONCLUSIONS: These studies demonstrate that the biomembrane-mimicking coating of COL/HEP multilayers is a simple and effective strategy to endow combined biological performances of pHA orbital implants and to potentially reduce implant-related complications.

A comparative study of identical VMAT plans with and without jaw tracking technique.

The unwanted radiation transmission through the multileaf collimators could be reduced by the jaw tracking technique which is commercially available on Varian TrueBeam accelerators. On the basis of identical plans, this study aims to investigate the dosimetric impact of jaw tracking on the volumetric-modulated arc therapy (VMAT) plans. Using Eclipse treatment planning system (TPS), 40 jaw-tracking VMAT plans with various tumor volumes and shapes were optimized. Fixed jaw plans were created by editing the jaw coordinates of the jaw-tracking plans while other parameters were identical. The deliverability of this artificial modification was verified using COMPASS system via three-dimentional gamma analysis between the measurement-based reconstruction and the TPS-calculated dose distribution. Dosimetric parameters of dose-volume histogram (DVH) were compared to assess the improvement of dose sparing for organs at risk (OARs) in jaw-tracking plans. COMPASS measurements demonstrated that over 96.9% of structure volumes achieved gamma values less than 1.00 at criteria of 3 mm/3%. The reduction magnitudes of maximum and mean dose to various OARs ranged between 0.06% ~ 6.76% (0.04 ~ 7.29 Gy) and 0.09% ~ 7.81% (0.02 ~ 2.78 Gy), respectively, using jaw tracking, agreeing with the disparities of radiological characteristics between MLC and jaws. Jaw tracking does not change the delivery efficiency and total monitor units. The dosimetric comparison of VMAT plans with and without jaw tracking confirms the physics hypotheses that reduced transmission through tracking jaws will reduce doses to OARs without sacrificing the target dose coverage because it is meant to be covered by radiation beams going through the opening.

Mandible evolution in the Scarabaeinae (Coleoptera: Scarabaeidae) and adaptations to coprophagous habits.

INTRODUCTION: The astonishing spectrum of scarabaeine lifestyles makes them an attractive group for studies in entomology and evolutionary biology. As a result of adaptions to specific food substrates and textures, the mouthparts of dung beetles, particularly the mandible, have undergone considerable evolutionary changes and differ distinctly from the presumptive ancestral conditions of the Coleoptera and Polyphaga. The possible functions of dung beetle mouthparts and the evolution of dung feeding have been controversial for decades. RESULTS: In this study, 187 scarabs representing all tribes of the Scarabaeinae and the major lineages within the Scarabaeoidea, along with three major feeding types within the Scarabaeoidea (omnivory, phytophagy and coprophagy), were studied. Based on geometric morphometric and three-dimensional (3D) reconstruction approaches, morphological differences in mandibles among the three feeding types were identified. The ancestral forms of the mandible within the Scarabaeinae were reconstructed and compared with those of modern species. The most recent common ancestor of the Scarabaeinae fed on soft materials, and the ancestor of the Scarabaeinae and the Aphodiinae was in an evolutionary transition between processing more solid and softer substrates. CONCLUSIONS: Coprophagy originated from omnivorous ancestors that were very likely saprophagous. Furthermore, phytophagy may also have originated from omnivory. In addition, our study addresses the integration and modularity of geometric morphometric data in a phylogenetic context.

Optimization of paeonol-loaded microparticle formulation by response surface methodology.

In this study, a central composite rotatable design based on response surface methodology (RSM) was employed to design and formulate an appropriate paeonol microparticle formulation. Five levels of a three-factor, rotatable, central composite design were used to evaluate the critical formulation variables. The optimum conditions for preparing paeonol-loaded microparticles were predicted to be: polyvinyl alcohol (PVA) content (2.84%), the ratio of drug to polymer (6.88) and the stirring rate (1007.59 rpm). The optimized responses for production yield and loading efficiency were found to be 68.86% and 55.90%, respectively, and the particle size were 23.27 ± 0.76 µm and the sorting coefficient (σ) was 0.732. Furthermore, in vitro release study suggested that microparticle could be a suitable delivery system in treating skin disease for its sustained release of drug. In conclusion, RSM can be successfully used to optimize the effect of formulation variables.

TNF-α promotes expression of inflammatory factors by upregulating nicotinamide adenine dinucleotide phosphate oxidase-2 expression in human gingival fibroblasts.

Background/purpose: Periodontitis is a chronic infectious disease. The oxidative stress environment can cause or exacerbate the inflammation in periodontitis. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) may be the most important source of reactive oxygen species (ROS) in periodontal tissues. The pathological mechanism of periodontitis may be related to the increased ROS caused by enhanced NOX activity. The purpose was to investigate the effect of tumor necrosis factor (TNF-α) on inflammatory cytokines and ROS, and the role of NOX-2 in human gingival fibroblasts (HGFs). Materials and methods: HGFs were cultured and divided into the normal control group (NC group) and the inflammatory model group (TNF-α group) induced by 10 ng/ml TNF-α. Thereafter, NOX-2 siRNA was used to knock down NOX-2 gene expression. Quantitative real-time PCR was applied to detect IL-6, MCP-1, and NOX-2 mRNA levels. The levels of IL-6 and MCP-1 protein were examined by ELISA. The level of NOX-2 was evaluated by Western blot. ROS expression was measured by the fluorescence microplate. Results: The mRNA and protein expression levels of IL-6, MCP-1, and NOX-2 were significantly increased, and the expression of ROS was significantly elevated in response to 10 ng/ml TNF-α. Compared with the si-NC group, the mRNA and protein expression levels of IL-6 and MCP-1 were significantly down-regulated and ROS expression was significantly decreased in the si-NOX2 group stimulated by 10 ng/ml TNF-α. Conclusion: TNF-α promotes the expression of NOX-2 in human gingival fibroblasts and enhances the expression of inflammatory factors and ROS in human gingival fibroblasts through the upregulation of NOX-2 partly.

Peptide-TLR7/8a-Coordinated DNA Vaccines Elicit Enhanced Immune Responses against Infectious Diseases.

DNA vaccines represent an innovative approach for the immunization of diverse diseases. However, their clinical trial outcomes are constrained by suboptimal transfection efficiency and immunogenicity. In this work, we present a universal methodology involving the codelivery of Toll-like receptor 7/8 agonists (TLR7/8a) and antigen gene using TLR7/8a-conjugated peptide-coated poly(ß-amino ester) (PBAE) nanoparticles (NPs) to augment delivery efficiency and immune response. Peptide-TLR7/8a-coated PBAE NPs exhibit advantageous biophysical attributes, encompassing diminutive particle dimensions, nearly neutral ζ potential, and stability in the physiological environment. This synergistic approach not only ameliorates the stability of plasmid DNA (pDNA) and gene delivery efficacy but also facilitates subsequent antigen production. Furthermore, under optimal formulation conditions, the TLR7/8a-conjugated peptide coated PBAE NPs exhibit a potent capacity to induce robust immune responses. Collectively, this nanoparticulate gene delivery system demonstrates heightened transfection efficacy, stability, biodegradability, immunostimulatory effect, and low toxicity, making it a promising platform for the clinical advancement of DNA vaccines.

Comparison of 4- or 6-implant supported immediate full-arch fixed prostheses: A retrospective cohort study of 217 patients followed up for 3-13 years.

PURPOSE: Choosing four or six implants to support immediate full-arch fixed prostheses (FAFPs) is still controversial worldwide. This study aims to analyze and compare the long-term results of All-on-4 and All-on-6. MATERIALS AND METHODS: This retrospective cohort study enrolled 217 patients rehabilitated with 1222 implants supporting 271 FAFPs, including 202 prostheses supported by 4 implants (All-on-4 group) and 69 prostheses supported by 6 implants (All-on-6 group), and followed up for 3-13 years. Implant survival, prosthesis survival, complications, and implant marginal bone loss (MBL) were evaluated and compared between two groups. Patient characteristics including age, gender, jaw, opposite dentition condition, smoking habit, bruxism, bone quantity and quality, cantilever length (CL), prosthesis material, and oral hygiene were analyzed to assess their influence on the clinical results of the two groups. Six surgeons and three prosthodontists who performed FAFPs more than 5 years were invited for questionnaires, to assess patient- and clinician-related influences on implant number. RESULT: In general, All-on-4 group indicated no significant difference with All-on-6 group in the implant survival (implant-level: hazard ratio [HR] = 1.0 [95% confidence interval (CI): 0.8-1.2], P = 0.96; prosthesis-level: HR = 0.8 [95% CI: 0.3-1.8], P = 0.54), prosthesis survival (odds ratio [OR] = 0.8 [95% CI: 0.3-2.8], P = 0.56), biological complications (OR = 0.9 [95% CI: 0.5-1.8], P = 0.78), technical complications of provisional prosthesis (OR = 1.3 [95% CI: 0.7-2.3], P = 0.42), technical complications of definitive prosthesis (OR = 1.1 [95% CI: 0.6-2.2], P = 0.33) and the 1st, 5th, and 10th year MBL (P = 0.65, P = 0.28, P = 0.14). However, for specific covariates, including elderly patients, opposing natural/fixed dentition, smoking, bruxism, long CL, low bone density, and all acrylic provisional prostheses, All-on-6 was more predictable in some clinical measurements than All-on-4. The implant prosthodontists and the medium-experienced clinicians showed significant preference for All-on-6 (P < 0.05). CONCLUSION: Based on this study, the long-term clinical results showed no significant difference between All-on-4 and All-on-6 groups in general. However, for some specific characteristics, All-on-6 seemed to be more predictable in some clinical measurements than All-on-4. For the clinicians' decision-making, medium-experienced clinicians and the implant prosthodontists showed significant preference for All-on-6.

The pH-responsive zeolitic imidazolate framework nanoparticle as a promising immune-enhancing adjuvant for anti-caries vaccine.

OBJECTIVES: Streptococcus mutans (S. mutans) is the main aetiologic bacterium of dental caries, whose protein antigen (PAc) has been administered as an anti-caries vaccine. In addition, several fusion proteins or PAc combined with adjuvants were used as anti-caries vaccines to improve the relatively weak immunogenicity of PAc. However, there are no nanoparticle-based adjuvants with good biocompatibility, excellent biodegradability, or the high loading performance of antigens used for anti-caries vaccines. This study aimed to prepare an innovative nanoparticle-based anti-caries vaccine and evaluate immune responses elicited by this vaccine in vitro and in vivo. METHODS: In this study, an anti-caries vaccine was prepared by an antigen of recombinant protein PAc from S. mutans and an adjuvant of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) synthesized using a hydrothermal method. Then, mice were administrated intranasally by ZIF-8@PAc vaccine, and immune responses were evaluated. RESULTS: ZIF-8 NPs not only greatly improved the internalization of the antigen but also released the PAc protein after degradation of ZIF-8 NPs in lysosomes for the further processing and presentation of antigen-presenting cells. In addition, ZIF-8@PAc induced significantly more potent PAc-specific serum IgG and saliva IgA antibodies, a higher splenocyte proliferation index, higher levels of the cytokines IL-4, IL-6, IL-10, IL-17A and IFN-γ, and a higher percentage of mature DCs and CD4+ memory T cells in vivo. CONCLUSIONS: The ZIF-8 NPs, as an anti-caries vaccine adjuvant-assisted antigen PAc, elicit significantly potent immune responses, aiding in the further prevention of dental caries. CLINICAL SIGNIFICANCE: Vaccine immunotherapy is an attractive strategy for prevention and treatment of dental caries. The ZIF-8@PAc vaccine can induce significantly high level of immune responses in this study, which indicates great potential for prevention and treatment of caries.