17ß-estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A-NLRC5 axis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17ß-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms. METHODS: Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining. RESULTS: The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown. CONCLUSION: E2 promoted the progression of TMJOA.

Fabricating oxygen self-supplying 3D printed bioactive hydrogel scaffold for augmented vascularized bone regeneration.

Limited cells and factors, inadequate mechanical properties, and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds. Herein, we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure. The hydrogel scaffold possesses the characteristics of extracellular matrix; Meanwhile, the fabricated hybrid double network structure by polyacrylamide and CaCl2-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability. Furthermore, the O2 generated by CaO2 nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8, which can significantly promote cell viability and proliferation in vitro, as well as angiogenesis and osteogenic differentiation with the assistance of Zn2+. More significantly, the synergy of O2 and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need, which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo. Overall, this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.

Idiopathic ventricular arrhythmia originating from the vicinity of lateral tricuspid annulus: the precise origin and anatomical concerns.

BACKGROUND: Although the electrcardiographic and electrophysiological properties of ventricular arrhythmias (VA) from the vicinity of lateral tricuspid annulus (TA) have been reported in previous studies, their precise site of origin have not been addressed. OBJECTIVE: To describe the precise origin of lateral TA-VA and the relevant anatomy. METHODS: Consecutive patients with idiopathic lateral TA-VAs were reviewed and analyzed. Three-dimensional mapping system combined with intracardiac echocardiography (ICE) was used for anatomical reconstruction, mapping, and ablation. RESULTS: During the study period, 63 patients with lateral TA-VAs were included. Under ICE view, a prominent enfoldment structure was observed under the valve along lateral TA. The muscular bundle was documented in all patients (100%) within the sub-valvular enfoldment with an average number and diameter of 4±2 and 4.10±0.73mm, respectively. Initial ablation was attempted via the antegrade approach in 15 patients but succeeded in none. To reach the ventricular side of TA, the catheter needed to enter ventricular chamber and retroflexed toward the atrial side with a reverse curve. The earliest activation site was found at the valvular end of muscular bundles in 51 of the 63 (80.9%) patients with a local activation time of -26.78±4.63ms. The VAs were eliminated after an average of 4±2 seconds of ablations. CONCLUSION: The ventricular adjacent to the lateral TA exhibits a sub-valvular enfoldment-like structure, which is rich in muscular bundles and serves as the origin of TA-VAs in most patients. To reach the origins, a reverse technique is required.

Biomechanical evaluation of various rigid internal fixation modalities for condylar-base-associated multiple mandibular fractures: A finite element analysis.

Condylar-base-associated multiple mandibular fractures are more prevalent than single ones. Direct trauma to mandibular symphysis, body or angle are prone to induce indirect condylar fracture. However, little is known about the effects of various rigid internal fixation modalities in condylar base for relevant multiple mandibular fractures, especially when we are confused in the selection of operative approach. Within the finite element analysis, straight-titanium-plate implanting positions in condylar base contained posterolateral zone (I), anterolateral zone (II), and intermediate zone (III). Von Mises stress (SS) in devices and bone and mandibular displacement (DT) were solved, while maximum values (SSmax and DTmax) were documented. For rigid internal fixation in condylar-base-and-symphysis fractures, I + II modality exhibited least SSmax in screws and cortical bone and least DTmax, I + III modality exhibited least SSmax in plates. For rigid internal fixation in condylar-base-and-contralateral-body fractures, I + III modality exhibited least SSmax in screws and cortical bone, I + II modality exhibited least SSmax in plates and least DTmax. For rigid internal fixation in condylar-base-and-contralateral-angle fractures, I + III modality exhibited least DTmax. The findings suggest that either I + II or I + III modality is a valid guaranty for rigid internal fixation of condylar base fractures concomitant with symphysis, contralateral body or angle fractures.

High expression of ACTL6A leads to poor prognosis of oral squamous cell carcinoma patients through promoting malignant progression.

OBJECTIVE: The aim was to research ACTL6A's role in oral squamous cell carcinoma (OSCC). METHODS: OSCC and normal samples were obtained from patients and public databases. GSEA was performed. CIBERSORT was utilized to analyze immune landscape. Kaplan-Meier survival analysis and multivariate Cox regression analysis were conducted. After knocking down ACTL6A, we performed MTT assay, transwell assays, and flow cytometry to detect the impact of knockdown. RESULTS: ACTL6A expressed higher in OSCC samples than normal samples. The CNV and mutation rate of TP53 was higher in ACTL6A high-expression group. TFs E2F7 and TP63 and miRNA hsa-mir-381 were significantly related to ACTL6A. ACTL6A could influence immune microenvironment of OSCC. Knockdown of ACTL6A inhibited OSCC cells' proliferation, migration, and invasion. ACTL6A was able to predict OSCC prognosis independently. CONCLUSION: ACTL6A expressed higher in OSCC than normal samples and it could be used as an independent prognostic marker in OSCC patients.

Characteristics and outcome of patients with left atrial appendage closure in China: a single-center experience.

BACKGROUND: Clinical characteristics and long-term data on the safety and efficacy of LAAC in preventing cerebrovascular accident and thromboembolism among Chinese patients with non-valvular AF (NVAF) remain limited. METHODS: Data of consecutive NVAF patients who underwent LAAC at Beijing Anzhen Hospital, Capital Medical University, from June 1, 2014, to December 31, 2021, were collected and analyzed retrospectively. The primary effectiveness endpoint was the composite endpoint of stroke/transient ischemic attack, systemic embolism, and death from cardiovascular causes. The primary safety endpoint is the severe bleeding defined by the LAAC Munich consensus. RESULTS: Of the 222 patients enrolled, the mean age was 66.90 ± 9.62 years, with a majority being male (77.03%). Many patients are non-paroxysmal AF (71.19%) with a median duration of AF of 4.00 years. The mean CHA2DS2-VASc score was 3.78 ± 1.49, and the mean HAS-BLED score was 1.68 ± 0.86. Thromboembolic events (76.58%) were the most common indication for LAAC. The device, technical, and procedural success rates were 98.65%, 98.65%, and 93.69%, respectively. The anticoagulation continuation rate was 56.36%, 31.25%, and 22.60% at 3-, 6- and 12 months post-procedure, respectively. Throughout a mean 2.81 years of follow-up, the incidence of the primary efficacy endpoint was 4.27 per 100 patient-years, predominantly attributable to stroke/TIA (3.12 per 100 PYs). Five patients experienced major bleeding during the follow-up period. Post-procedure imaging revealed minimal complications, with only one substantial peri-device leak. Device-related thrombus occurred in 2.33% of patients, resolving with anticoagulation. CONCLUSION: The study demonstrates that LAAC is a safe and effective alternative option for Chinese patients with AF, with a high success rate, few complications as well as fewer long-term adverse outcome events.

Association Between Number of Missing Teeth and Hyperlipidemia: The TCLSIH Cohort Study.

Background: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population. Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1-2, and ≥3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia. Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) (P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) (P for trend < 0.01). Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association.

Antihypertensive effect and mechanism of the traditional recipe of medicine food homology (Buyang Huanwu Decoction) in China: Meta analysis and network pharmacological exploration.

Background: Hypertension has become a part of the lives of many people worldwide. With the development, an increasing number of people have begun to control their hypertension through products of medicine food homology, such as Buyang Huanwu Decoction (BYHWD). However, there has been no objective review of the regulation of hypertension by BYHWD. Methods: As of 9 October 2023, this review made a detailed search of nine databases to look for random controlled trials (RCTs) focused on the use of BYHWD for treating hypertension. This was followed by network pharmacological analysis, and molecular docking assessment using AutoDockTools to explore the mode of action. Results: BYHWD was effective in reducing SBP (MD: 0.767; 95 % CI: 0.629, 0.905; p = 0.000), DBP (MD: 0.427; 95 % CI: 0.292, 0.561; p = 0.000), 24h SBP (MD: 0.665; 95 % CI: 0.368, 0.962; p = 0.000), 24h DBP (MD: 0.547; 95 % CI: 0.318, 0.777; p = 0.000), dSBP (MD: 0.625; 95 % CI: 0.395, 0.855; p = 0.000), dDBP (MD: 0.632; 95 % CI: 0.401, 0.862; p = 0.000), nSBP (MD: 0.859; 95 % CI: 0.340, 1.377; p = 0.001), nDBP (MD: 0.704; 95 % CI: 0.297, 1.112; p = 0.001), pv (MD: 1.311; 95 % CI: 0.363, 2.259; p = 0.007) and NIHSS (MD: 1.149; 95 % CI: 0.100, 2.199; p = 0.032), and elevating CER (OR = 2.848; 95 % CI: 1.388, 5.843; p = 0.004). However, BYHWD did not significantly reduce HCY, and there was no significant difference in the incidence of AE. In terms of the mechanism of action, the main active ingredient of BYHWD is quercetin, and the core targets are AKT1, MMP9, and others. Molecular docking also showed that quercetin mainly interacts with the amino acid residue CYS-28 of MMP2. Second, the KEGG analysis showed that BYHWD mainly act on HIF-1, Apelin, and cGMP-PKG signalling pathways, and GO analysis showed that it related to the apical part of the cell, circulatory system processes, and nuclear receptor activity. Conclusion: BYHWD can lowered blood pressure, reduced plasma viscosity, and restored neurological function with good tolerability, and had no significant effect on HCY levels. This study further demonstrated that quercetin is the main active ingredient of BYHWD that acts via the AKT1 and HIF-1 signalling pathways. These results provide new guidance for people's dietary choices by the general public.

High-resolution mass spectrometry-based non-targeted metabolomics reveals toxicity of naphthalene on tall fescue and intrinsic molecular mechanisms.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous at relatively high concentrations by atmospheric deposition, and they are threatening to the environment. In this study, the toxicity of naphthalene on tall fescue and its potential responding mechanism was first studied by integrating approaches. Tall fescue seedlings were exposed to 0, 20, and 100 mg L-1 naphthalene in a hydroponic environment for 9 days, and toxic effects were observed by the studies of general physiological studies, chlorophyll fluorescence, and root morphology. Additionally, Ultra Performance Liquid Chromatography - Electrospray Ionization - High-Resolution Mass Spectrometry (UPLC-ESI-HRMS) was used to depict metabolic profiles of tall fescue under different exposure durations of naphthalene, and the intrinsic molecular mechanism of tall fescue resistance to abiotic stresses. Tall fescue shoots were more sensitive to the toxicity of naphthalene than roots. Low-level exposure to naphthalene inhibited the electron transport from the oxygen-evolving complex (OEC) to D1 protein in tall fescue shoots but induced the growth of roots. Naphthalene induced metabolic change of tall fescue roots in 12 h, and tall fescue roots maintained the level of sphingolipids after long-term exposure to naphthalene, which may play important roles in plant resistance to abiotic stresses.

Valsartan attenuates LPS-induced ALI by modulating NF-κB and MAPK pathways.

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common respiratory disease characterized by persistent hypoxemia and an uncontrolled inflammatory response. Valsartan, an angiotensin II type 1 receptor antagonist, is clinically used to treat hypertension and has anti-inflammatory and antioxidant effects on gefitinib-induced pneumonia in rats. However, the potential therapeutic effects of valsartan on lipopolysaccharide (LPS)-induced ALI remain unclear. This study investigated the protective role of valsartan in LPS-induced ALI and its underlying mechanisms. Methods: LPS-treated BEAS-2B cells and ALI mouse model were established. BEAS-2B cells were treated with LPS (10 µg/mL) for 24h, with or without valsartan (20, 40, and 80 µM). For ALI mouse models, LPS (5 mg/kg) was administered through intratracheal injection to treat the mice for 24h, and valsartan (10 or 30 mg/kg) was injected intraperitoneally twice 2 h before and 12 h after the LPS injection. Pulmonary functional parameters were examined by an EMKA pulmonary system. Hematoxylin and eosin staining, flow cytometry, CCK-8 assay, qRT-PCR, ELISA, immunofluorescence, Western blotting, and related commercial kits were used to assess the pathological damage to the lungs, neutrophil recruitment in the lung tissue and bronchoalveolar lavage fluid (BALF), cell viability, inflammation, oxidative activity, and mucus production, respectively. Potential mechanisms were further explored using network pharmacology and Western blotting. Results: Valsartan rescued LPS-reduced cell viability of BEAS-2B cells, improved the pulmonary function, ameliorated pathological lung injury in mice with ALI, ameliorated LPS-induced neutrophil recruitment in BALF and lung tissue of mice, attenuated oxidative stress by increasing the level of SOD and decreasing that of MDA and GSSG, inhibited LPS-induced MUC5AC overproduction, decreased the LPS-induced increase in expression of pro-inflammatory cytokines/chemokines including TNF-α, IL-6, IL-1ß, CXCL-1 and CXCL-2, and restored the expression of anti-inflammatory IL-10. Mechanistic studies showed that valsartan inhibits LPS-induced phosphorylation of nuclear factor-kappa B (NF-κΒ) and mitogen-activated protein kinases (MAPKs) including P38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in both LPS-treated cells and the mouse model of ALI. Conclusion: Valsartan protects against LPS-induced ALI by attenuating oxidative stress, reducing MUC5AC production, and attenuating the inflammatory response that may involve MAPK and NF-κΒ pathways.

P2Y13 receptor involved in HIV-1 gp120 induced neuropathy in superior cervical ganglia through NLRP3 inflammasome activation.

Cardiac autonomic neuropathy resulting from human immunodeficiency virus (HIV) infection is common; however, its mechanism remains unknown. The current work attempted to explore the function and mechanism of the P2Y13 receptor in HIV-glycoprotein 120 (gp120)-induced neuropathy in cervical sympathetic ganglion. The superior cervical ganglion (SCG) of the male SD rat was coated with HIV-gp120 to establish a model of autonomic neuropathy. In each group, we measured heart rate, blood pressure, heart rate variability, sympathetic nerve discharge and cardiac function. The expression of P2Y13 mRNA and protein in the SCG was tested by real-time polymerase chain reaction and western blotting. Additionally, this study focused on identifying the protein levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD), interleukin (IL)-1ß and IL-18 in the SCG using western blotting and immunofluorescence. In gp120 rats, increased blood pressure, heart rate, cardiac sympathetic nerve activity, P2Y13 receptor levels and decreased cardiac function could be found. P2Y13 shRNA or MRS2211 inhibited the above mentioned changes induced by gp120, suggesting that the P2Y13 receptor may be engaged in gp120-induced sympathetic nerve injury. Moreover, the levels of NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18 in the gp120 group were increased, while significantly decreased by P2Y13 shRNA or MRS2211. Therefore, the P2Y13 receptor is involved in gp120-induced sympathetic neuropathy, and its molecular mechanism shows an association with the activation of the NLRP3 inflammasome, followed by GSDMD formation along with the release of inflammatory factors including IL-1ß and IL-18. This article is part of the Special Issue on "Purinergic Signaling: 50 years".

Electrophysiological characteristics and ablation of ventricular arrhythmias originating from the intramural basal inferior septum.

AIMS: The electrocardiographic and electrophysiological characteristics of ventricular arrhythmia (VA) arising from the intramural basal inferior septum (BIS) have not been specifically addressed to date. The aim of the current study was to characterize intramural BIS-VA and distinguish it from those with endocardial origins besides clarifying the anatomical configurations of the pyramidal space. METHODS AND RESULTS: Fifty-five consecutive patients undergoing catheter ablation of VAs from BIS were identified and divided into three groups: the left ventricular (LV)-BIS group (n = 28), right ventricular (RV)-BIS group (n = 8), and intramural group (Intra, n = 19). Compared with the LV-BIS and RV-BIS groups, patients in the Intra group presented with no adequate earliest activation time at the two-sided BIS and epicardial coronary system [right: 7.79 ± 2.38 vs. left: 7.16 ± 2.59 vs. the middle cardiac vein (MCV): 6.26 ± 1.73 ms, P = 0.173] and poor-matched pacing-produced QRS at each site. Under the intracardiac echocardiography view, the pyramidal base was the broadest part of the septum and served as the division of the two-sided BIS. Focal ablation yielded promising acute-term and long-term procedural success in the LV-BIS and RV-BIS groups. But for the Intra group, VAs disappeared only after stepwise ablation successively targeted early preferential exit. After follow-up, three patients in the Intra group had recurrent VA, and all of them were treated well by a redo procedure or drug therapy. CONCLUSION: Intramural VAs were relatively common in the BIS region in our series. Intra-procedural mapping was important to distinguish the intramural VAs from other VAs by comparing the local activation time and pacing mapping. Procedural success could be achieved by stepwise ablation on the counterpart sides of the BIS and within the MCV.

Consensus on the preparation margin and restoration margin in ceramic esthetic rehabilitation.

In esthetic rehabilitation, methods used to enhance the margin quality have always been the focus and difficulty of improving the level of diagnosis and treatment, prevention and treatment of complications, and collaboration between clinicians and technicians. However, it is impeded by the ambiguous definition and classification of margin, unstandardized tooth preparation, manufacturing process of restoration, and lack of reliable means of checking the quantitative requirements of preparation or restoration. The digital technologies that are increasingly applied, such as intra-oral scanner, impression scanner, and computerized numerical control cutting machine, have strict requirements about margin quality. Failure of recognizing margins by these scanners will hinder the digital process of diagnosis and treatment. Even if these sharp and narrow margins are successfully scanned, they cannot be milled accurately. To overcome these problems, this article demonstrated the clear and complete definition of preparation margin and restoration margin, as well as their subclassifications, by analyzing the target restoration space from a geometric perspective. Practical approaches to measuring the margin width and inspecting the margin quality were proposed. The new and full understanding and proposal about preparation margin and restoration margin characterized by measurements will effectively support the thoroughly digitalized process of esthetic rehabilitation using porcelain in fixed prosthodontics, which is based on the guidance of values.

Using tea nanoclusters as ß-lactamase inhibitors to cure multidrug-resistant bacterial pneumonia: A promising therapeutic strategy by Chinese materioherbology.

ß-lactamase, a kind of hydrolase in multi-drug resistant pathogens, can hydrolyze ß-lactam antibiotics and make these kinds of antibiotics invalid. Small-molecular inhibitors about the enzyme and their mechanism are widely investigated but they may result in unavoidable adverse reactions and drug-resistance. Herein, we propose a new therapeutic strategy of Chinese materioherbology, in which herbal medicine or traditional Chinese medicinal herbs can be employed as biological functional materials or refreshed/excited by means of materialogy. Natural tea nanoclusters (TNCs) were extracted from tea to inhibit ß-lactamase. Different from the mechanism of small-molecular inhibitors inhibiting enzymes by binding to the corresponding active sites, the TNCs as a cap cover the protein pocket and create a spatial barrier between the active sites and antibiotics, which was named "capping-pocket" effect. TNCs were combined with amoxicillin sodium (Amo) to treat the methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in mice. This combinatorial therapy remarkably outperforms antibiotic monotherapy in reducing MRSA infections and the associated inflammation in mice. The therapeutic strategy exhibited excellent biosafety, without any side effects, even in piglets. Hence, TNCs have great clinical value in potentiating ß-lactam antibiotic activity for combatting multi-drug resistant pathogen infections and the "pocket capping" effect can guide the design of new enzyme inhibitors in near future.

Cyclic fatigue resistance of two nickel-titanium instruments in different curving angles: a comparative study

The cyclic resistance of ProTaper Universal (size 25/08) and ProTaper Next (size 25/06) instruments was compared in artificial canals with different curvatures in this study. A total of 30 ProTaper Universal and 30 ProTaper Next instruments were divided into 6 groups (n = 10) and were operated into artificial canals with 3 different angles of curvature (45°, 60°, 90°). The canal length was kept consistent in this study. The number of cycles to fracture (NCF) was counted until file fracture occurred, at which point, the length of the fragment was measured. The data were analyzed statistically using ANOVA complemented by the Tukey test (p < 0.05). Cross sections of the fractured files were scanned by an electron microscope. In the fatigue test, the ProTaper Next displayed more resistance in 45° and 60° canals (p < 0.05), whereas ProTaper Universal exhibited a better operability in 90° canals (p < 0.05). The average length of the fragments from ProTaper Next was significantly shorter than that from ProTaper Universal in 90° canals (p < 0.05). The cross sections of the fractured surfaces became flatter when the curvature angles decreased from 90° to 45°. ProTaper Next was more reliable when shaping in curved canals, whereas ProTaper Universal was more sui for the preparation of root canals with severe curvatures.