Potential role of salivary lactic acid bacteria in pathogenesis of oral lichen planus.

BACKGROUND: Emerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is noteworthy that a decreased abundance of Streptococcus, a member of lactic acid bacteria (LAB) in OLP patients has been commonly reported, indicating its possible effect on OLP. This study aims to investigate the composition of LAB genera in OLP patients by high-throughput sequencing, and to explore the possible relationship between them. METHODS: We collected saliva samples from patients with OLP (n = 21) and healthy controls (n = 22) and performed 16 S rRNA gene high-throughput sequencing. In addition, the abundance of LAB genera was comprehensively analyzed and compared between OLP and HC group. To verify the expression of Lactococcus lactis, real time PCR was conducted in buccal mucosa swab from another 14 patients with OLP and 10 HC. Furthermore, the correlation was conducted between clinical severity of OLP and LAB. RESULTS: OLP and HC groups showed similar community richness and diversity. The members of LAB, Lactococcus and Lactococcus lactis significantly decreased in saliva of OLP cases and negatively associated with OLP severity. In addition, Lactococcus and Lactococcus lactis showed negative relationship with Fusobacterium and Aggregatibacter, which were considered as potential pathogens of OLP. Similarly, compared with healthy controls, the amount of Lactococcus lactis in mucosa lesion of OLP patients was significantly decreased. CONCLUSIONS: A lower amount of Lactococcus at genus level, Lactococcus lactis at species level was observed in OLP cases and associated with disease severity. Further studies to verify the relationship between LAB and OLP, as well as to explore the precise mechanism is needed.

Fluid flow reconstruction around a free-swimming sperm in 3D.

We investigate the dynamics and hydrodynamics of a human spermatozoa swimming freely in 3D. We simultaneously track the sperm flagellum and the sperm head orientation in the laboratory frame of reference via high-speed high-resolution 4D (3D+t) microscopy, and extract the flagellar waveform relative to the body frame of reference, as seen from a frame of reference that translates and rotates with the sperm in 3D. Numerical fluid flow reconstructions of sperm motility are performed utilizing the experimental 3D waveforms, with excellent accordance between predicted and observed 3D sperm kinematics. The reconstruction accuracy is validated by directly comparing the three linear and three angular sperm velocities with experimental measurements. Our microhydrodynamic analysis reveals a novel fluid flow pattern, characterized by a pair of vortices that circulate in opposition to each other along the sperm cell. Finally, we show that the observed sperm counter-vortices are not unique to the experimental beat, and can be reproduced by idealised waveform models, thus suggesting a fundamental flow structure for free-swimming sperm propelled by a 3D beating flagellum.

Consumers' risk perception, market demand, and firm innovation: Evidence from China.

Major product safety incidents often cause widespread concern among consumers, and these product safety incidents will stimulate consumers' psychology, change their risk perception, and affect the demand for products and services of risk consumers. The change in consumer demand will eventually lead to a change in firm innovation decisions. Using Chinese firm-level data, this paper employs the news reporting of the Bawang event as a quasi-natural experiment to study the impact of risk perception changes on innovation. The empirical results of this study show that increasing consumers' risk perception caused by the negative news coverage of defective products motivates firms to increase their innovation. The effects are heterogeneous, where firms with private ownership and in developed regions are more likely to increase innovation activities. This study suggests that the relationship between consumers' risk perception and firm innovation is primarily driven by market demand. Moreover, the positive effects of risk perception on innovation are more prominent for downstream firms and those having a smaller technological distance.

Effect of structural support size and position on depressed tibial plateau fractures: A finite element analysis.

Objective: Structural support for depressed tibial plateau fractures is receiving increasing attention. Currently, there has been little biomechanical evaluation of structural support. This work aimed to investigate the effect of structural support size and position on fracture fixation stability. Methods: A split-depressed tibial plateau fracture model was created according to the fracture map. Cortical screws combined with structural filler were used for fracture fixation. The filler diameter was set to small, medium and large, and the filler position was set to the center and offset by 1, 2 and 3 mm to study the effect of position and size on stability. Results: The maximum stress on the implant in all scenarios occurs at the lower contact surface between the anterior screw and the filler. Increased support size resulted in increased mean maximum screw stress, depressed fragment axial displacement and separated fragment transverse displacement (screw stress: 266.6 ± 37.7 MPa vs. 266.7 ± 51.0 MPa vs. 273.8 ± 41.5 MPa; depressed displacement: 0.123 ± 0.036 mm vs. 0.133 ± 0.049 mm vs. 0.158 ± 0.050 mm; separated displacement: 0.402 ± 0.031 mm VS 0.412 ± 0.047 mm VS 0.437 ± 0.049 mm). The larger the offset of the support position was, the larger the peak screw stress and the larger the reduction loss of depressed and separated fragment reduction, regardless of the support size. The medium support combined with the central position presented the minimum of peak stress and reduction loss. Cortical bone was below 2 % and trabecular strain was below 10 % for all scenarios. Conclusion: Central placement of structural support provides superior stability for the treatment of depressed tibial plateau fractures compared to the eccentric placement. When a support is placed centrally, optimal stability is achieved when the diameter matches the diameter of the depressed region. Thus, the utilization of equal-diameter fillers to provide central support appears to be an ideal selection for depressed tibial plateau fractures.

FOXF1 promotes tumor vessel normalization and prevents lung cancer progression through FZD4.

Cancer cells re-program normal lung endothelial cells (EC) into tumor-associated endothelial cells (TEC) that form leaky vessels supporting carcinogenesis. Transcriptional regulators that control the reprogramming of EC into TEC are poorly understood. We identified Forkhead box F1 (FOXF1) as a critical regulator of EC-to-TEC transition. FOXF1 was highly expressed in normal lung vasculature but was decreased in TEC within non-small cell lung cancers (NSCLC). Low FOXF1 correlated with poor overall survival of NSCLC patients. In mice, endothelial-specific deletion of FOXF1 decreased pericyte coverage, increased vessel permeability and hypoxia, and promoted lung tumor growth and metastasis. Endothelial-specific overexpression of FOXF1 normalized tumor vessels and inhibited the progression of lung cancer. FOXF1 deficiency decreased Wnt/ß-catenin signaling in TECs through direct transcriptional activation of Fzd4. Restoring FZD4 expression in FOXF1-deficient TECs through endothelial-specific nanoparticle delivery of Fzd4 cDNA rescued Wnt/ß-catenin signaling in TECs, normalized tumor vessels and inhibited the progression of lung cancer. Altogether, FOXF1 increases tumor vessel stability, and inhibits lung cancer progression by stimulating FZD4/Wnt/ß-catenin signaling in TECs. Nanoparticle delivery of FZD4 cDNA has promise for future therapies in NSCLC.

Oral mucosal changes in tight junction proteins in patients with oral lichen planus.

OBJECTIVE: This study aimed to investigate the expression of tight junction, its distribution pattern in oral lichen planus samples and its potential association with the severity of oral lichen planus. MATERIALS AND METHODS: Cross-sectional study designs were conducted. Transcriptome sequencing was conducted using oral mucosal tissues from 22 patients with oral lichen planus and 11 healthy controls. Immunohistochemistry and quantitative reverse transcription PCR were performed to verify the expression of claudin-1, claudin-4, occludin and zonula occludens-1 in oral mucosal tissues from another 30 patients with oral lichen planus and 26 healthy controls. The relationship between tight junction protein expression and oral lichen planus severity was explored using correlation analysis. RESULTS: 5603 and 2475 differentially expressed genes were upregulated and downregulated respectively, in oral lichen planus tissues. KEGG analysis showed that tight junctions including CLDN1, CLDN4, OCLN and TJP1 were downregulated in oral lichen planus. Claudin-1, claudin-4, occludin and zonula occludens-1 expression was verified to be significantly lower in oral lichen planus. Furthermore, correlation analyses showed that decreased occludin expression was positively related to oral lichen planus severity. CONCLUSION: Decreased expression of TJ barrier proteins may be associated with the development of oral lichen planus.

Polygonatum sibiricum Saponin Prevents Immune Dysfunction and Strengthens Intestinal Mucosal Barrier Function in Cyclophosphamide-Induced Immunosuppressed BALB/c Mice.

The aim of this study was to explore the immunomodulatory effect of Polygonatum sibiricum saponin (PS) in a cyclophosphamide-induced (Cy) immunosuppression mice model. Oral administration of PS by gavage effectively alleviated weight loss caused by Cy and increased the index of immune organs. PS promoted the proliferation of splenic lymphocytes and T cell subsets (CD3+, CD355+, CD4+/CD8+) and relieved the xylene-induced inflammatory response and Cy-induced increase of serum hemolysin. Moreover, PS increased serum levels of lactate dehydrogenase and acid phosphatase. PS elevated serum level of cytokines and immunoglobulins (TNF-α, IFN-γ, IL-4, IL-6, IL-ß, SIgA, and IgG) and the expression of mRNA of IL-10, TNF-α, and IL-6 in the spleen. Increased mRNA expression of tight junction protein (ZO-1, Mucin2, Occludin) expression and protein expression of IL-6/MyD88/TLR4 in the small intestine showed that PS exhibited a restorative effect on intestinal mucosal injury caused by cyclophosphamide. Oral PS prevented Cy-induced decline in leukocytes, red blood cells, lymphocytes, hemoglobin concentrations, and neutrophils, providing evidence for alleviating hematopoietic disorders. In addition, PS increased SOD and NO levels, reduced MDA levels, and improved oxidative damage in the liver. These findings demonstrate that PS has the potential to be developed as a supplemental agent for alleviating immunosuppression caused by chemotherapeutic agents.

Biomechanical analysis of titanium-alloy and biodegradable implants in dual plate osteosynthesis for AO/ASIF type 33-C2 fractures.

Background and objective: Treating geriatric osteoporotic distal femur fractures has always presented challenges, but developing biodegradable materials has brought new opportunities for therapeutic intervention. Despite this progress, there currently needs to be more evidence-based biomechanical guidelines for using dual plate fixation and biodegradable materials in treating osteoporotic comminuted distal femoral fractures.In this study, finite element analysis was conducted to evaluate the mechanical effectiveness of different implant materials (titanium alloys, biodegradable materials, and combinations of both) in the fixation of physiological and osteoporotic distal femoral fractures. Methods: We constructed finite element models of 33-C2 fractures and three types of plates: the Lateral Less Invasive Stabilization System (LISS) plate, the titanium-alloy medial plate (TAP), and the biodegradable plate (BP). To evaluate the biomechanical advantages in both physiological femur (PF) and osteoporotic femur (OF) conditions, three scenarios were developed: LISS + TAP, LISS + BP, and double biodegradable plates (DBPs). Five loading conditions were applied to measure structural stiffness, fracture micromotion, and implant stress: medio-lateral four-point bending, antero-posterior four-point bending, axial loading, torsional loading, and sideways falling. Several parameters were examined, including peak Von Mises Stress (VMS) of the femur and lateral plate, maximum displacement, bending angle, torsional angle of fracture, and risk of fracture. Results: In four-point bending tests, the lateral plate of the DBPs group exhibited a slightly lower peak VMS compared to the LISS + TAP and LISS + BP groups. When subjected to axial loading, the stiffness values of the LISS + TAP (OF) were 1.42 times and 1.86 times higher than LISS + BP (OF) and DBPs (OF) groups, and the peak VMS of lateral plate of DBPs (OF) construct was approximately 2% and 16% lower than that of the LISS + TAP (OF) and LISS + BP (OF) constructs. Under torsional loading, DBPs (OF) demonstrated rotational stiffness that was respectively 2% and 52% greater than that of LISS + TAP (OF) and LISS + BP (OF). Regarding the peak VMS of femur, the values of DBPs (OF) were almost 8% and 15% lower than those of LISS + TAP (OF) and LISS + BP (OF). Conclusions: The use of DBPs at 11.33 GPa facilitated early mobilization of load-bearing joints but exhibited limited ability to support full weight-bearing activities. Though LISS + TAP met practical strength requirements, one should consider the potential biological irritation and stress shielding. Thus, employing a combination of biodegradable and metal internal fixation is a valid approach to effectively treat weight-bearing joint fractures in clinical practice.

[Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through transcriptome sequencing].

OBJECTIVE: To detect key genes of local glucocorticoid therapy in oral lichen planus (OLP) through transcriptome sequencing. METHODS: The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa, Peking University Hospital of Stomatology from November 2019 to March 2023. Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min, 3 times daily for 4 weeks. The patients' signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome. Their mucosa samples were collected before treatment. After isolating total RNA, transcriptome sequencing was performed. The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software, and the Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes (DEGs), accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone. RESULTS: After 4 weeks treatment by topical dexamethasone, 13 cases of the 28 OLP patients responding well with the sign score reducing from 7.0 (4.5, 9.0) to 5.0 (3.0, 6.3), pain score decreasing from 5.0 (2.0, 5.5) to 2.0 (0.0, 3.5), oral health impact profile lessening from 5.0 (3.5, 9.0) to 1.0 (0.0, 5.0) significantly (P<0.01) were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group. There were no significant differences of demographic and baseline levels of clinical features, especially disease severity between these two groups. A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between effective group and ineffective group. KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8, CTNNA3, MYL2 and MYLPF were associated with leukocyte transendothelial migration, while downregulated genes were significantly enriched in tumor necrosis factor (TNF), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB) signaling pathways, and cortisol synthesis and secretory. CONCLUSION: High expressions of CLDN8, CTNNA3, MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone, while patients with high expression genes of inflammation pathway such as TNF, IL-17, NF-κB and cortisol synthesis and secretion received poor effect.