Glutathione peroxidase 4 restrains temporomandibular joint osteoarthritis progression by inhibiting ferroptosis.

There are few effective therapeutic strategies for temporomandibular joint osteoarthritis (TMJOA) due to the unclear pathology and mechanisms. We aimed to confirm the roles of GPX4 and ferroptosis in TMJOA progression. ELISA assay was hired to evaluate concentrations of ferroptosis-related markers. The qRT-PCR assay was hired to assess gene mRNA level. Western blot assay and immunohistochemistry were hired to verify the protein level. CCK-8 assay was hired to detect cell viability. Human fibroblast-like synoviocytes (FLSs) were cultured to confirm the effects of GPX4 and indicated inhibitors, and further verified the effects of GPX4 and ferroptosis inhibitors in TMJOA model rats. Markers of ferroptosis including 8-hidroxy-2-deoxyguanosine (8-OHdG) and iron were notably increased in TMJOA tissues and primary OA-FLSs. However, the activity of the antioxidant system including the glutathione peroxidase activity, glutathione (GSH) contents, and glutathione/oxidized glutathione (GSH/GSSG) ratio was notably inhibited in TMJOA tissues, and the primary OA-FLSs. Furthermore, the glutathione peroxidase 4 (GPX4) expression was down-regulated in TMJOA tissues and primary OA-FLSs. Animal and cell experiments have shown that ferroptosis inhibitors notably inhibited ferroptosis and promoted HLS survival as well as up-regulated GPX4 expression. Also, GPX4 knockdown promoted ferroptosis and GPX4 overexpression inhibited ferroptosis. GPX4 also positively regulated cell survival which was the opposite with ferroptosis. In conclusion, GPX4 and ferroptosis regulated the progression of TMJOA. Targeting ferroptosis might be an effective therapeutic strategy for TMJOA patients in the clinic.

Improved LEACH Protocol Based on Underwater Energy Propagation Model, Parallel Transmission, and Replication Computing for Underwater Acoustic Sensor Networks.

Underwater acoustic sensor networks (UASNs) are critical to a range of applications from oceanographic data collection to submarine surveillance. In these networks, efficient energy management is critical due to the limited power resources of underwater sensors. The LEACH protocol, a popular cluster-based protocol, has been widely used in UASNs to minimize energy consumption. Despite its widespread use, the conventional LEACH protocol faces challenges such as an unoptimized cluster number and low transmission efficiency, which hinder its performance. This paper proposes an improved LEACH protocol for cluster-based UASNs, where the cluster number is optimized with an underwater energy propagation model to reduce energy consumption, and a transmission scheduling algorithm is also employed to achieve conflict-free parallel data transmission. Replication computing is introduced to the LEACH protocol to reduce the signaling in the clustering and data transmission phases. The simulation results show that the proposed protocol outperforms several conventional methods in terms of normalized average residual energy, average number of surviving nodes, average round when the first death node occurs, and the number of packets received by the base station.

Nickel-Catalyzed Three-Component Unsymmetrical Bis-Allylation of Alkynes with Alkenes: A Density Functional Theory Study.

Density functional theory (DFT) characterizations were employed to resolve the structural and energetic aspects and product selectivities along the mechanistic reaction paths of the nickel-catalyzed three-component unsymmetrical bis-allylation of alkynes with alkenes. Our putative mechanism initiated with the in situ generation of the active catalytic species [Ni(0)L2] (L = NHC) from its precursors [Ni(COD)2, NHC·HCl] to activate the alkyne and alkene substrates to form the final skipped trienes. This proceeds via the following five sequential steps: oxidative addition (OA), ß-F elimination, ring-opening complexation, C-B cleavage and reductive elimination (RE). Both the OA and RE steps (with respective free energy barriers of 24.2 and 24.8 kcal·mol-1) contribute to the observed reaction rates, with the former being the selectivity-controlling step of the entire chemical transformation. Electrophilic/nucleophilic properties of selected substrates were accurately predicted through dual descriptors (based on Hirshfeld charges), with the chemo- and regio-selectivities being reasonably predicted and explained. Further distortion/interaction and interaction region indicator (IRI) analyses for key stationary points along reaction profiles indicate that the participation of the third component olefin (allylboronate) and tBuOK additive played a crucial role in facilitating the reaction and regenerating the active catalyst, ensuring smooth formation of the skipped triene product under a favorably low dosage of the Ni(COD)2 catalyst (5 mol%).

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1ß. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

Bioactivity of the cannabigerol cannabinoid and its analogues - the role of 3-dimensional conformation.

Cannabinoids are naturally occurring bioactive compounds with the potential to help treat chronic illnesses including epilepsy, Parkinson's disease, dementia and multiple sclerosis. Their general structures and efficient syntheses are well documented in the literature, yet their quantitative structure-activity relationships (QSARs), particularly 3-dimensional (3-D) conformation-specific bioactivities, are not fully resolved. Cannabigerol (CBG), an antibacterial precursor molecule for the most abundant phytocannabinoids, was characterised herein using density functional theory (DFT), together with selected analogues, to ascertain the influence of the 3D structure on their activity and stability. Results showed that the CBG family's geranyl chains tend to coil around the central phenol ring while its alkyl side-chains form H-bonds with the para-substituted hydroxyl groups as well as CH⋯π interactions with the aromatic density of the ring itself, among other interactions. Although weakly polar, these interactions are structurally and dynamically influential, effectively 'stapling' the ends of the chains to the central ring structure. Molecular docking of the differing 3-D poses of CBG to cytochrome P450 3A4 resulted in lowered inhibitory action by the coiled conformers, relative to their fully-extended counterparts, helping explain the trends in the inhibition of the metabolic activity of the CYP450 3A4. The approach detailed herein represents an effective method for the characterisation of other bioactive molecules, towards improved understanding of their QSARs and in guiding the rational design and synthesis of related compounds.

Effects of cryopreservation on the biomechanical properties of dentin in cryopreserved teeth: An in-vitro study.

This study focused on the biomechanical properties and microstructural changes in dentin of teeth in different age groups after cryopreserved for different durations. Ninety third molars from three age groups (youth group, middle-age group, and elderly group), were collected and randomly divided into three groups according to freezing time at -196 °C (7 days, 30 days, and 90 days). Control group was shored at ordinary temperature. After rewarming, the compressive strength and elastic modulus of the dentin were measured with an electronic universal tester. Scanning electron microscopy was used to evaluate the microstructure of dentin after cryopreservation. After cryopreservation, the compressive strength of the teeth in each experimental group was not significantly different from control group. With the increase of freezing time and age, dentin's elastic modulus showed a decreasing trend. There were statistically significances between the control group and freezing 90d group, freezing 7d and 90d group, youth and middle-aged group, youth and elderly group (P < 0.05). Both freezing time and age factors were significant for the elastic modulus of dentin(P＜0.05). There was no interaction effect for age and freezing time. In transverse sections of scanning electron microscopy, the dentinal tubule became narrower, partially occluded, and more easily adhered to impurities in the long freezing time and elderly group. In longitudinal sections, with freezing time and age, the inner wall of the dentinal tubules became rough especially in the aged group cryopreserved for 90 days. No significant microcracks exited in any of the longitudinal sections of dentin.

Effectiveness and prognostic factors of different minimally invasive surgeries for vertebral compression fractures.

BACKGROUND: The aging of China's population has led to an increase in the incidence rate of osteoporosis, which indirectly increases the risk of OVCF in osteoporosis patients. Low back pain is the main symptom of OVCF, and severe patients can further develop kyphosis. Although the conservative treatment of OVCF can effectively control the patient's condition, long-term bed rest will increase the risk of OVCF complications. Minimally invasive surgery is a common solution for OVCF. METHODS: 100 OVCF patients admitted to our hospital from January 2021 to January 2022 are selected for analysis and randomly divided into PVP group and PKP group, 50 cases in each group. The PVP group and the PKP group undergo PVP and PKP operations respectively. The differences in efficacy indicators and adverse reactions are compared, and the multivariate Logistic regression method is used to analyze the influencing factors of postoperative secondary fractures in patients with vertebral compression fractures. RESULTS: Compared with the PVP group, the total effective rate of PKP group is significantly increased, and the VAS, ODI score, kyphotic Cobb Angle, lateral distribution rate of bone cement and bone cement leakage rate are significantly decreased (P < 0.05). Age ≥ 80 years old, female, glucocorticoid use, lateral distribution of bone cement and bone cement leakage are significantly higher in the proportion of secondary fractures and are independent risk factors for postoperative secondary fractures in patients with OVCF. CONCLUSION: PKP surgery has a higher efficacy in the treatment of OVCF patients, which can reduce the incidence of pain, adverse reactions and promote the recovery of kyphotic Cobb Angle. PKP surgery has a higher value in the treatment of OVCF. In addition, the influencing factors of secondary fracture after minimally invasive surgery in OVCF patients include age, gender, glucocorticoid use, bone cement distribution pattern, bone cement leakage, etc.

A Review of the Motion Planning and Control Methods for Automated Vehicles.

The motion planning and control method of automated vehicles, as the key technology of automated vehicles, directly affects the safety, comfort, and other technical indicators of vehicles. The planning module is responsible for generating a vehicle driving path. The control module is responsible for driving the vehicle. In this study, we review the main methods and achievements in motion planning and motion control for automated vehicles. The advantages and disadvantages of various planning and control methods are comparatively analyzed. Finally, some predictions and summaries based on the existing research results and trends are proposed. Through this analysis, it is believed that various types of algorithms will be further integrated in the future to complement each other's strengths and weaknesses. The next area of research will be to establish more accurate vehicle models to describe vehicle motion, improve the generalization-solving ability of algorithms, and enhance the planning and control of integrated 'human-vehicle-road' traffic systems.

Can Locked Fibula Nail Replace Plate Fixation for Treatment of Acute Ankle Fracture? A Systematic Review and Meta-Analysis.

The standard surgical treatment for unstable ankle fractures involves open reduction and internal fixation (ORIF) with plates. However, ORIF has been associated with several complications, such as soft tissue irritation, wound infection, and nerve injury. Previous studies have shown that closed reduction and internal fixation with locked intramedullary nails (LIMNs) yields satisfactory efficacy in the treatment of ankle fractures and is associated with low complication rates. Therefore, a systematic review and meta-analysis of randomized controlled trials is imperative to provide evidence on whether or not LIMN fixation is comparable to or superior than traditional ORIF. We conducted a comprehensive literature search in the PubMed, Cochrane Library and EMBASE databases. A total of 4 randomized controlled trials involving 359 participants who suffered ankle fractures were included in this systematic review and meta-analysis. The results showed that the LIMN fixation group was statistically significant in terms of functional outcomes at the 3-month follow-up and wound-related complications. There was no statistical advantage for patients in the LIMN fixation group in terms of nonwound-related complications, total complications, or mid-term follow-up functional outcomes. There was no statistical difference between the LIMN and ORIF groups regarding operation time and quality of reduction. We believe LIMN fixation is a viable option for the treatment of unstable ankle fractures in both young and elderly individuals.

High directionality of surface radiation for surface emitting distributed feedback lasers.

Improving the directionality of surface radiation is the key to increase the output power and the differential quantum efficiency of grating-coupled surface-emitting distributed feedback lasers. We proposed a scheme to realize the high directionality of surface radiation. In the structure, the second-order grating is fabricated on the p-side of the epitaxial wafer. A SiO2/Si3N4 multilayer reflector arranged above the grating is used to redirect the upward-diffracted beam. The design of the intermediate layer between the grating and the reflector is an important part of achieving high directionality, because the adjustment of its thickness can be used to phase the redirected light with the downward-diffracted light. The calculation results show that the directionality of this structural scheme can reach more than 98% which meets the device requirements. This design provides a reference for surface-emitting distributed feedback lasers with high performance and high stability.

High-power distributed feedback lasers with high-order surface curved gratings.

A novel, to the best of our knowledge, broad-area distributed feedback laser with high-order surface curved gratings has been fabricated based on standard near ultraviolet lithography. The characteristics of increasing output power and mode selection are achieved simultaneously by using a broad-area ridge as well as an unstable cavity structure composed of curved gratings and a high-reflectivity coated rear facet. Suppression of high-order lateral modes is realized by setting current injection/non-injection regions and asymmetric waveguides. This DFB laser emitting around 1070 nm has achieved a spectral width of 0.138 nm and a maximum output power of 915 mW kink-free optical power. The threshold current and side-mode suppression ratio of the device are 370 mA and 33 dB, respectively. The simple manufacturing process and stable performance give this high-power laser broad application prospects in the fields of light detection and ranging, laser pumps, optical disk access, etc.

A novel strategy for orthogonal genetic regulation on different RNA targeted loci simultaneously.

No current RNA-targeted interference tools have been reported to simultaneously up and down-regulate different gene expressions. Here we characterized an RNA-targeted genetic regulatory strategy composed of a flap endonuclease 1 (FEN1) and specific mis-hairpin DNA probes (mis-hpDNA), to realize the orthogonal genetic regulation. By targeting mRNA, the strategy hindered the translation and silenced genes in human cells with efficiencies of ~60%. By targeting miRNA, the strategy prevented the combination of miRNA to its specific mRNA and increased this mRNA expression by about 3-folds. In combination, we simultaneously performed CXCR4 gene knock-down (~50%) and EGFR gene activation (1.5-folds) in human cells. Although the functional property can be further improved, this RNA-targeted orthogonal genetic regulating strategy is complementary to classical tools.

Aluminium catalysed oligomerisation in cement-forming silicate systems.

Alumino-silicates form the backbone of structural materials including cements and the concrete they form. However, the nanoscale aspects of the oligomerisation mechanisms elongating the (alumino-)silicate chains is not fully clarified; the role of aluminium in particular. Herein, we explore and contrast the growth of silicate and alumino-silicate oligomers by both neutral and anionic mechanisms, with focus on the influence of Al on oligomer structure and stability. Further, the spontaneity of chain lengthening in the absence and presence of Al of differing coordination (Al-IV, V, VI) was characterised. Result trends showed Al-IV facilitating oligomerisation in neutral conditions, with respect to Si only systems, effectively promoting longer chain formation and stabilisation. The anionic pathway similarly showed Al reducing the overall energetic barriers to oligomerisation. In both conditions, Al's coordinative and structural flexibility, at O-Al-O hinge points in particular, was responsible for the lowering of the energetic expense for oligomerisation. The results and implications resolved herein are informative for chain formation and stability for bulk material properties of alumino-silicate materials such as cements, where the aluminosilicate systems are dominated by short chains of 2-5 units in length.

Simulation analysis of the near and far fields of an ARROW laser array with narrow slots.

We studied a periodic slot-based three-core antiresonant reflecting optical waveguide laser array structure. Periodic narrow slots are used to define functional areas in the array, which directly avoids the epitaxial regrowth in the fabrication of traditional antiguide arrays. A comparative study confirmed the feasibility of the scheme. Moreover, the calculation results show that, with the increase of the width of the antiguide core, the power ratio of the main lobe in the far field increases, and the divergence angle of the main lobe and the angle between the secondary lobe and the main lobe decrease. This law provides ideas for the optimization of the array structure.

Simulation analysis of high-order high-duty-cycle surface gratings.

High-order surface grating distributed feedback lasers are known to operate with a fundamental mode, narrow linewidth, high power, and high slope efficiency. The adoption of high-order surface gratings can avoid epitaxial re-growth necessary for the fabrication of conventional buried gratings, which simplifies the fabrication process and reduces device cost. It is essential for the design and optimization of device structure to clarify the influence of the change of grating structure parameters on grating characteristics (coupling and loss). Based on Lumerical's Mode Solutions and multiple grating samples, we evaluated the coupling and loss coefficients of surface gratings as a function of duty cycle, order, and V-groove topography. As the order increases, the duty cycle corresponding to the peak value of the grating coupling coefficient increases gradually and approaches one. The grating coupling coefficient decreases with increasing order but increases at some specific orders. At high duty cycles, the width of the grating groove corresponding to the peak of the coupling coefficient remains substantially in the range of 100-150 nm, which is close to the length of a quarter-wavelength in the grating groove filling material. Regarding the grating groove morphology, the fabrication difficulty of the V-shaped groove grating is obviously less than that of the rectangular groove grating, but its coupling coefficient is slightly smaller than that of the rectangular shaped groove grating of the same depth. The larger the V-shaped groove width, the smaller the peak coupling coefficient and the corresponding sidewall inclination will be. Losses decrease with increasing duty cycle and decreasing sidewall inclination of the V-groove.

DNA and RNA editing without sequence limitation using the flap endonuclease 1 guided by hairpin DNA probes.

Here, we characterized a flap endonuclease 1 (FEN1) plus hairpin DNA probe (hpDNA) system, designated the HpSGN system, for both DNA and RNA editing without sequence limitation. The compact size of the HpSGN system make it an ideal candidate for in vivo delivery applications. In vitro biochemical studies showed that the HpSGN system required less nuclease to cleave ssDNA substrates than the SGN system we reported previously by a factor of ∼40. Also, we proved that the HpSGN system can efficiently cleave different RNA targets in vitro. The HpSGN system cleaved genomic DNA at an efficiency of ∼40% and ∼20% in bacterial and human cells, respectively, and knocked down specific mRNAs in human cells at a level of ∼25%. Furthermore, the HpSGN system was sensitive to the single base mismatch at the position next to the hairpin both in vitro and in vivo. Collectively, this study demonstrated the potential of developing the HpSGN system as a small, effective, and specific editing tool for manipulating both DNA and RNA without sequence limitation.

Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer.

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment.

Rössler-network with time delay: Univariate impulse pinning synchronization.

Rössler had a brilliant and successful life as a scientist during which he published a benchmark dynamical system by using an electronic circuit interpreting chemical reactions. This is our contribution to honor his splendid erudite career. It is a hot topic to regulate a network behavior using the pinning control with respect to a small set of nodes in the network. Besides pinning to a small number of nodes, small perturbation to the node dynamics is also demanded. In this paper, the pinning synchronization of a coupled Rössler-network with time delay using univariate impulse control is investigated. Using the Lyapunov theory, a theorem is proved for the asymptotic stability of synchronization in the network. Simulation is given to validate the correctness of the analysis and the effectiveness of the proposed univariate impulse pinning controller.

Convex hull principle for classification and phylogeny of eukaryotic proteins.

This study quantitatively validates the principle that the biological properties associated with a given genotype are determined by the distribution of amino acids. In order to visualize this central law of molecular biology, each protein was represented by a point in 250-dimensional space based on its amino acid distribution. Proteins from the same family are found to cluster together, leading to the principle that the convex hull surrounding protein points from the same family do not intersect with the convex hulls of other protein families. This principle was verified computationally for all available and reliable protein kinases and human proteins. In addition, we generated 2,328,761 figures to show that the convex hulls of different families were disjoint from each other. The classification performs well with high and robust accuracy (95.75% and 97.5%) together with reasonable phylogenetic trees validate our methods further.

Effects of dam impoundment on the soil seed bank in a plateau wetland of China.

Dam impoundment, which rapidly changes hydrologic regimes and greatly alters aquatic environments, plays a critical role in the seed germination and seedling growth of wetland plants, especially influencing their seed banks. In this study, a soil seed bank experiment was carried out along a water level gradient for the Lake Lashi wetland in the Northwest Yunnan Plateau of China. The objectives of this study were to determine the effect, driver and dynamic mechanism of dam impoundment on the soil seed bank of plateau wetlands using partial least squares (PLS) regression and chaotic dynamic methods. The results showed that the soil seed bank had significant differences in seed density, species composition, and water ecotype of the plant species between the flood zone (perennially flooded area, seasonally flooded area, and flood plain area) and nonflood zone (control area) in the plateau wetland. The seed bank density was obviously lower in the perennially flooded area and higher in the seasonally flooded area and flood plain area, with values that were 39.88%, 153.53%, and 146.47% that of the control area, respectively. After dam impoundment, the number of plant species gradually increased; however, the dominance of the dominant species became less obvious, and the species diversity indices decreased significantly, e.g., by 15.47% for the Simpson diversity index and 72.39% for the Shannon Wiener diversity index. Our study showed that dam impoundment has made the Lake Lashi wetland complex chaotic ecosystem switch between order and disorder through self-organization and that the species composition of the soil seed bank continuously experienced self-adaptation. These results provide a reference for scientific evaluations of the effects of dam impoundment on wetland ecosystems and provide guidance for the protection and management of plateau wetland ecosystems.