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Introduction: Orthodontic tooth movement (OTM) involves complex interactions between mechanical forces and periodontal tissue adaptation, mainly mediated by periodontal ligament cells, including periodontal ligament stem cells (PDLSCs), osteoblasts, and osteoclasts. Dopamine (DA), a neurotransmitter known for its critical role in bone metabolism, is investigated in this study for its potential to enhance osteogenic differentiation in PDLSCs, which are pivotal in OTM. This study examined the potential of DA to facilitate OTM by binding to DA receptors (D1R and D2R) and activating the ERK1/2 signaling pathway. We propose that DA's interaction with these receptors on PDLSCs could enhance osteogenic differentiation, thereby accelerating bone remodeling and reducing the duration of orthodontic treatments, which offering a novel approach to improve clinical outcomes in orthodontic care. Methods: This study utilized a rat OTM model, micro-CT, histological analyses, and in vitro assays to investigate dopamine's effect on osteogenesis. PDLSCs were cultured and treated with DA, and cytotoxicity, osteogenic differentiation, gene and protein expression assessed. Results: Dopamine administration significantly increased trabecular bone density and osteogenic marker expression in an OTM rat model. In vitro, DA at 10 nM optimally promoted human PDLSCs osteogenesis without affecting proliferation. Blocking DA receptors or inhibiting the ERK1/2 pathway attenuated these effects, underscoring the importance of dopaminergic signaling in tension-induced osteogenesis during OTM. Conclusion: Taken together, our study reveals that local dopamine administration at a concentration of 10 nM not only enhances tension-induced osteogenesis in vivo but also significantly promotes osteogenic differentiation of PDLSCs in vitro through D1 and D2 receptor-mediated ERK1/2 signaling pathway activation.

Abstract Ferroptosis is an important pathological mechanism of chronic heart failure (CHF). This study aimed to investigate the protective mechanism of Astragaloside IV (AS-IV) on CHF rats by integrating bioinformatics and ferroptosis. CHF-related targets and ferroptosis-related targets were collected. After the intersection, the common targets were obtained. The PPI network of the common targets was constructed, and topological analysis of the network was carried out. The target with the highest topological parameter values was selected as the key target. The key target p53 was obtained through bioinformatics analysis, and its molecular docking model with AS-IV was obtained, as well as molecular dynamics simulation analysis. The rat models of CHF after myocardial infarction were established by ligation of left coronary artery and treated with AS-IV for 4 weeks. AS-IV treatment significantly improved cardiac function in CHF rats, improved cardiomyocyte morphology and myocardial fibrosis, reduced mitochondrial damage, decreased myocardial MDA and Fe2+ content, increased GSH content, inhibited the expression of p53 and p-p53, and up-regulated the expression of SLC7A11 and GPX4. In conclusion, AS-IV improved cardiac function in CHF rats, presumably by regulating p53/SLC7A11/GPX4 signaling pathway and inhibiting myocardial ferroptosis.

Abstract Background Temporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA. Methods We disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3β/β-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles. Results Jet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3β/β-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3β/β-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3β/β-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3β/β-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.

Objective: To explore the effect of amyloid-β peptide (Aβ) on mandibular condyle to develop a new treatment for postmenopausal women with Temporomandibular joint osteoarthritis. Methods: A murine bone loss model was established by ovariectomy. Microstructure parameters of the condyle were measured by microcomputed tomography before and after intraperitoneal injection with Aβ. Flow cytometry, Alizarin red staining, RT-qPCR assays, FITC/PI staining, Oil Red O staining and western blotting were used to evaluate the effect of Aβ on the osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs). Results: In vivo, condylar microstructure parameters increased. Serum osteoprotegerin and procollagen type 1 N propeptide increased in a dose-dependent manner after the injection of Aβ, which were opposite the changes observed in c-terminal telopeptides of type I collagen, tumor necrosis factor-α and the high serum level of leptin. In vitro, Aβ promoted calcium nodule formation in the cells. The expression of ALP, Runx2, osteorix and osteocalcin increased significantly. The expression of mRNAs related to the Wnt signaling pathway was significantly upregulated, which could be blocked by DKK1. Conclusion: Aβ can reverse bone loss in the mandibular condyle in ovariectomized mice through promoting the osteogenic differentiation of mBMSCs via the Wnt pathway.

This study selects Beijing from 1980 to 2020 as the research area, utilizing high temporal resolution land use data to analyze through the habitat quality module of the InVEST model. Unlike previous research, this study employs the Theil-Sen Median method and Mann-Kendall test to analyze the trend changes in habitat quality more accurately. This method has significant advantages in dealing with non-linear and non-normally distributed data over long time series, providing a more accurate and reliable analysis of habitat quality trends. Methodologically, the study first collects and organizes the land use type data of Beijing from 1980 to 2020, then uses the habitat quality module of the InVEST model to process and analyze the data of each year, assessing the impact of different land use types on habitat quality. Subsequently, the Theil-Sen Median method and Mann-Kendall test are used to analyze the time series trend of habitat quality, to identify and quantify the trend and significance of habitat quality changes. The results show that over the past 40 years, the area of construction land in Beijing has significantly expanded, leading to a compression of other types of land. The spatial distribution of habitat quality shows a clear difference between the two sides divided by a line connecting the northeast and southwest, with the west side being the area of good habitat quality and the east side being poorer. In the past 10 years, the overall habitat quality has improved, but most areas still show a decreasing trend, especially in the western and northern mountainous areas where habitat quality has significantly declined. Based on these findings, it is recommended that future urban planning and land management should pay more attention to the protection and improvement of habitat quality, especially the restoration work for areas with poor habitat quality.

Abstract Background The evolutionarily conserved protein FBXO9 acts as a substrate receptor for the SKP1-cullin-1-RBX1 ubiquitin ligase and is implicated in cancer, exhibiting either tumor-suppressive or oncogenic effects depending on the specific tumor type. However, their role in lung cancer metastasis remains unclear. Methods Lentiviral vectors carrying miRNA-based shRNA sequences for gene-specific knockdown were generated, and Lenti-CRISPR-Cas9 vectors containing gene-specific sgRNA sequences were designed. Gene overexpression was achieved using doxycycline-inducible lentiviral constructs, while gene knockdown or knockout cells were generated using shRNA and CRISPR-Cas9, respectively. Functional assays included migration, clonogenic survival assays, tumor sphere assays, and protein interaction studies using mass spectrometry, immunoprecipitation, and immunoblot analysis. Results This study identified FBXO9 as a crucial regulator that suppresses lung cancer cell migration, tumor sphere growth and restricts metastasis. We showed that FBXO9 facilitates the ubiquitination of the catalytic subunit A (ATP6V1A) of the Vacuolar-type H+-ATPase (V-ATPase), resulting in its interaction with the cytoplasmic chaperone HSPA8 and subsequent sequestration within the cytoplasm. This process hinders the assembly of functional V-ATPase, resulting in reduced vesicular acidification. In contrast, depletion of FBXO9 reduced ATP6V1A ubiquitination, resulting in increased V-ATPase assembly and vesicular acidification, thus promoting pro-metastatic Wnt signaling and metastasis of lung cancer cells. Furthermore, we demonstrated the effectiveness of inhibitors targeting V-ATPase in inhibiting lung cancer metastasis in a mouse model. Finally, we established a correlation between lower FBXO9 levels and poorer survival outcomes in patients with lung cancer. Conclusion These findings collectively elucidate the critical role of FBXO9 in regulating V-ATPase assembly and provide a molecular basis for FBXO9’s function in inhibiting lung cancer metastasis. This highlights the potential therapeutic opportunities of FBXO9 supplementation.

Abstract Background Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by chronic synovitis as well as cartilage and bone destruction. Halofuginone hydrobromide (HF), a bioactive compound derived from the Chinese herbal plant Dichroa febrifuga Lour., has demonstrated substantial anti-arthritic effects in RA. Nevertheless, the molecular mechanisms responsible for the anti-RA effects of HF remain unclear. Methods This study employed a combination of network pharmacology, molecular docking, and experimental validation to investigate potential targets of HF in RA. Results Network pharmacology analyses identified 109 differentially expressed genes (DEGs) resulting from HF treatment in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses unveiled a robust association between these DEGs and the IL-17 signaling pathway. Subsequently, a protein-protein interaction (PPI) network analysis revealed 10 core DEGs, that is, EGFR, MMP9, TLR4, ESR1, MMP2, PPARG, MAPK1, JAK2, STAT1, and MAPK8. Among them, MMP9 displayed the greatest binding energy for HF. In an in vitro assay, HF significantly inhibited the activity of inflammatory macrophages, and regulated the IL-17 signaling pathway by decreasing the levels of IL-17 C, p-NF-κB, and MMP9. Conclusion In summary, these findings suggest that HF has the potential to inhibit the activation of inflammatory macrophages through its regulation of the IL-17 signaling pathway, underscoring its potential in the suppression of immune-mediated inflammation in RA.

Abstract To integrate driver experience and heterogeneous vehicle platform characteristics in a motion-planning algorithm, based on the driver-behavior-based transferable motion primitives (MPs), a general motion-planning framework for offline generation and online selection of MPs is proposed. Optimal control theory is applied to solve the boundary value problems in the process of generating MPs, where the driver behaviors and the vehicle motion characteristics are integrated into the optimization in the form of constraints. Moreover, a layered, unequal-weighted MP selection framework is proposed that utilizes a combination of environmental constraints, nonholonomic vehicle constraints, trajectory smoothness, and collision risk as the single-step extension evaluation index. The library of MPs generated offline demonstrates that the proposed generation method realizes the effective expansion of MP types and achieves diverse generation of MPs with various velocity attributes and platform types. We also present how the MP selection algorithm utilizes a unique MP library to achieve online extension of MP sequences. The results show that the proposed motion-planning framework can not only improve the efficiency and rationality of the algorithm based on driving experience but can also transfer between heterogeneous vehicle platforms and highlight the unique motion characteristics of the platform.

Periodontal ligament stem cells (PDLSCs) are considered ideal cell sources for the regeneration of periodontal and alveolar bone tissue. Cytoskeleton Regulator RNA (CYTOR), a newly discovered long noncoding RNA, has been reported to function as competing endogenous RNA (ceRNA) and to be involved in many biological processes. However, its roles in PDLSC osteogenic differentiation remain unclear. Here, we firstly found CYTOR was mainly sublocalized in the cytoplasm of PDLSCs and CYTOR expression was increased during osteogenic differentiation of PDLSCs. By employing gain- and loss-of-function approaches, we then identified CYTOR overexpression promoted osteogenic differentiation of PDLSCs while CYTOR knockdown inhibited this process. Furthermore, bioinformatics analysis was utilized to show that both CYTOR and SOX11 mRNA contained the same seed sites for miR-6512-3p, which was further confirmed by dual luciferase reporter assay and RNA-binding protein immunoprecipitation. Notably, CYTOR conferred its functions by directly binding to miR-6512-3p and an inverse correlation between CYTOR and miR-6512-3p on the level on SOX11 and osteogenic differentiation of PDLSCs was obtained. Additionally, miR-6512-3p could bind to SOX11 mRNA 3′ UTR and repressed SOX11 expression. Moreover, level of SOX11 was significantly increased during osteogenic differentiation of PDLSCs. Knockdown of SOX11 attenuated the increasing effect of CYTOR overexpression on osteogenic differentiation of PDLSCs. Collectively, these data supported that CYTOR positively modulated the expression of SOX11 through competitively binding to miR-6512-3p, thus promoting osteogenic differentiation of PDLSCs. The CYTOR/miR-6512-3p/SOX11 axis could be a novel therapeutic target for periodontal regeneration medicine.

According to previous theories of aggression, positive outcome expectancy for aggression can predict aggression, while moral disengagement and negative outcome expectancy for aggression may, respectively, serve as mediators and moderators in this prediction process. To test the hypothesis, Study 1 first developed the Aggression Outcome Expectancy Questionnaire and examined its two-factor structure, which consists of positive and negative outcome expectancy for aggression. Next, 677 college students were recruited to participate in Study 2 and were asked to complete the Aggression Outcome Expectancy Questionnaire, Civic Moral Disengagement Questionnaire, and Buss–Perry Aggression Questionnaire. The findings indicated the following: (1) The Aggression Outcome Expectancy Questionnaire for college students demonstrated acceptable reliability and construct validity, confirming the two-factor structure of aggression outcome expectancy. (2) After controlling for sex and age, moral disengagement partially mediated the relationship between positive outcome expectancy and aggression. (3) Negative outcome expectancy for aggression moderated the effect of positive outcome expectancy on aggression, as well as moral disengagement. Specifically, negative outcome expectancy for aggression attenuated the positive predictive effect of positive outcome expectancy on aggression and moral disengagement. In conclusion, the present study extends our understanding of the motivational mechanism of aggression, offering a theoretical reference for preventing and intervening in aggressive behavior among college students.

Cellulose paper, a material that is naturally derived, low cost, lightweight, eco-friendly, and mechanically deformable, plays important roles in producing next-generation flexible electronics. Following the booms in the development of functional electronics, the soft actuators built from cellulose paper have attracted great attention. In this focused review, the milestones and recent achievements of cellulose paper-based actuators are summarized. Electro-, thermal, moisture and magnetic actuation mechanisms are utilized to acquire energy from external stimuli. Corresponding functional materials and available fabrication techniques like film assembly and layer deposition are described. Programmable actions for the emerging applications in bionics, paper grippers and robots are realized by pursuing different strategies to control the responding deformation. Along with a conclusion, the existing challenges and possible solutions in evaluating and improving the performance of cellulose paper are summarized in the final section.

The techniques that harvest mechanical energy from low-frequency, multidirectional environmental vibrations have been considered a promising strategy to implement a sustainable power source for wireless sensor networks and the Internet of Things. However, the obvious inconsistency in the output voltage and operating frequency among different directions may bring a hindrance to energy management. To address this issue, this paper reports a cam-rotor-based approach for a multidirectional piezoelectric vibration energy harvester. The cam rotor can transform vertical excitation into a reciprocating circular motion, producing a dynamic centrifugal acceleration to excite the piezoelectric beam. The same beam group is utilized when harvesting vertical and horizontal vibrations. Therefore, the proposed harvester reveals similar characterization in its resonant frequency and output voltage at different working directions. The structure design and modeling, device prototyping and experimental validation are conducted. The results show that the proposed harvester can produce a peak voltage of up to 42.4 V under a 0.2 g acceleration with a favorable power of 0.52 mW, and the resonant frequency for each operating direction is stable at around 3.7 Hz. Practical applications in lighting up LEDs and powering a WSN system demonstrate the promising potential of the proposed approach in capturing energy from ambient vibrations to construct self-powered engineering systems for structural health monitoring, environmental measuring, etc.

Nervous system is critically involved in bone homeostasis and osteogenesis. Dopamine, a pivotal neurotransmitter, plays a crucial role in sympathetic regulation, hormone secretion, immune activation, and blood pressure regulation. However, the role of dopamine on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) remains poorly understood. In this study, we firstly investigated the effect of dopamine on the apoptosis, proliferation, and osteogenic differentiation of rBMSCs. Dopamine did not, however, interfere with the apoptosis and proliferation of rBMSCs. Interestingly, dopamine suppressed the osteogenic differentiation of rBMSCs, as characterized by reduced ALP staining, ALP activity, mineralized nodule formation, and the mRNA and protein levels of osteogenesis-related genes (Col1a1, Alp, Runx2, Opn, and Ocn). Furthermore, dopamine inactivated AKT/GSK-3β/β-catenin signaling pathway. Treatment of LiCl (GSK-3β inhibitor) rescued the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. LY294002 (AKT inhibitor) administration exacerbated the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. Taken together, these findings indicate that dopamine suppresses osteogenic differentiation of rBMSCs via AKT/GSK-3β/β-catenin signaling pathway. Our study provides new insights into the role of neurotransmitters in bone homeostasis.

In order to collect mechanical energy from human motions on pavement without an obvious disturbance, a piezoelectric harvester for small displacement is proposed. A seesaw mechanism is utilized to transmit the pressure displacement to piezoelectric beams. Benefitting from the superiority of used axially deformed beams, the designed scheme can produce a higher voltage than the ones based on the conventional bending cantilever. Favorable electrical energy is achieved by the manufactured prototype under a displacement lower than 1 mm. Two practical applications, including charging a capacitor and powering an environmental sensing node, demonstrate the feasibility of this energy harvester in supplying power for engineering devices. The proposed device shows a favorable capacity to capture energy from humans walking on pavements. Also, this category of axially deformed beam could provide ideas for developing piezoelectric harvesters under small displacements.

PurposeOur study aims to examine the impact of definitive local therapy in prostate cancer patients with different metastatic sites.MethodsTotally, 5,849 patients diagnosed with metastatic prostate carcinoma from 2010 to 2014 were selected from Surveillance, Epidemiology, and End Results (SEER). Log-rank analyses, multivariable regression analysis, and Kaplan–Meier methods were used to assess prognostic impact of local treatment in patients with different metastatic sites. Survival curves and forest plots were also plotted to describe the prognostic value of definitive local therapy.ResultsIn our study, 159 patients received radical prostatectomy, and 62 received brachytherapy, while 5,628 did not receive local definitive local therapy. Survival analysis revealed that patients who received definitive local therapy had a better 5-year overall survival (OS) (P = 0.011) and cancer-specific survival (CSS) (P = 0.012). Multivariate regression analyses demonstrated that type of treatment was an independent prognostic indicator for OS (P = 0.011) and CSS (P = 0.012), along with age at diagnosis, chemotherapy, PSA level, and Gleason score. According to subgroup analysis, patients with bone metastasis or distant lymph node (LN) metastasis were significantly more likely to benefit from definitive local therapy. In addition, forest plots demonstrated that RP group had significant favorable OS and CSS in subgroups of younger age at diagnosis, T2–3 stage, N0–1 stage, Gleason score =7 or ≥8, bone metastasis, and distant LN metastasis.ConclusionsOur study suggested that local therapy improved survival in prostate cancer patients with bone or distant LN metastasis. Furthermore, patients who were at T2–3 stage or Gleason score ≥7 also significantly benefit from definitive local therapy.

As the outfield load spectrum is so complicated that it cannot be used directly for test study in laboratory. This paper presents a method to determine load spectrum for high and low cycle combined fatigue of turbine mortise at elevated temperature through experimental and numerical method. First of all, the low cycle load spectrum with duration time is determined through cumulative damage rule. The rain flow counting method is applied to obtain main cycles and sub cycles, and then the stress cycle is converted into pulsation cycle (stress ratio=0) based on the S-N curve and the Goodman curve; Secondly, three groups of different amplitudes tests are established to determine the high cycle amplitude. Finally, another three groups of the high-low combined cycle fatigue (HLCCF) tests for turbine mortise of a certain type engine are carried out. The results show that the macro and micro failure modes are identical with outfield's, which verifies the accuracy of the conversion method.

Wetland plants are important components in constructed wetlands (CWs), and one of their most important functions in CWs is to purify the water. However, wetland plant litter can also increase eutrophication of water via decomposition and nutrient release, and few studies have focused on the interspecific variation in the decomposition rate and nutrient release of multiple plant species in CWs. Here a greenhouse litter-bag experiment was conducted to quantify the decomposition rates and nutrient release of 7 dominant macrophytes (2 floating plants and 5 emergent plants) in three types of water substrate. The results showed that plant litter species and growth forms significantly affected the litter mass losses. The nutrient release was significantly different among plant litter species, but not between floating and emergent plants. Litter traits, such as litter lignin, total nitrogen (TN) and total phosphorus (TP) can well predict the decomposition rates of submerged litter. These results indicated that submerging litter in water did not change the relationships between litter traits and litter decomposition rates, and leaching might play a more important role in the decomposition of submerged litter in CWs than that in other terrestrial ecosystems. These findings can provide suggestions for managers about the maintenance of constructed wetlands. [ABSTRACT FROM AUTHOR]

We monitored the water quality and hydrological conditions of a horizontal subsurface constructed wetland (HSSF-CW) in Beijing, China, for two years. We simulated the area-based constant and the temperature coefficient with the first-order kinetic model. We examined the relationships between the nitrogen (N) removal rate, N load, seasonal variations in the N removal rate, and environmental factors?such as the area-based constant, temperature, and dissolved oxygen (DO). The effluent ammonia (NH4+-N) and nitrate (NO3+-NO3) concentrations were significantly lower than the influent concentrations (p < 0.01, n = 38). The NO3--N load was significantly correlated with the removal rate (R2 = 0.96, p < 0.01), but the NH4+-N load was not correlated with the removal rate (R2 = 0.02, p > 0.01). The area-based constants of NO3--N and NH4+-N at 20 ?C were 27 ? 26 (mean ? SD) and 14 ? 10 m·year-1, respectively. The temperature coefficients for NO3--N and NH4+-N were estimated at 1.004 and 0.960, respectively. The area-based constants for NO3--N and NH4+-N were not correlated with temperature (p > 0.01). The NO3--N area-based constant was correlated with the corresponding load (R2 = 0.96, p < 0.01). The NH4+-N area rate was correlated with DO (R2 = 0.69, p < 0.01), suggesting that the factors that influenced the N removal rate in this wetland met Liebig's law of the minimum. [ABSTRACT FROM AUTHOR]