Prevalence and associated factors of health anxiety in patients with temporomandibular disorders.

OBJECTIVES: To investigate the prevalence and associated factors of health anxiety (HA) in patients with Temporomandibular Disorders (TMDs) using the 8-item Whiteley Index (WI-8) scale. MATERIALS AND METHODS: Three hundred and twenty-nine TMDs patients completed the Visual Analog Scale (VAS), WI-8, Jaw Functional Limitation Scale-8 (JFLS-8), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) scales. Clinical examinations were conducted following the Diagnostic Criteria for TMDs Axis I. RESULTS: The prevalence of HA among TMDs patients was 18.54%. Patients with HA had higher scores of VAS-current (p = 0.026), VAS-maximum (p = 0.024), VAS-average (p = 0.030), JFLS-8 (p < 0.001), GAD-7 (p < 0.001) and PHQ-9 (p < 0.001), lower maximum mouth opening (p = 0.016), lower proportion of structure-related TMDs (p = 0.028), and higher proportion of pain-related TMDs (p < 0.001) compared to those without HA. The correlation coefficient was 0.61 (p < 0.001) between WI-8 and GAD-7 and 0.64 (p < 0.001) between WI-8 and PHQ-9. CONCLUSION: Approximately one-fifth of patients with TMDs experienced HA. HA was associated with pain perception, functional limitations, depressive, and anxiety symptoms in individuals with TMDs. HA may contribute to heightened subjective pain experiences rather than structural changes in the TMJ.

Mitochondrial glycerol 3-phosphate dehydrogenase deficiency exacerbates lipotoxic cardiomyopathy.

Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.

CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects.

Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet-induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination-proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis.

Relationship Between Temporomandibular Joint Effusion, Pain, and Jaw Function Limitation: A 2D and 3D Comparative Study.

Purpose: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation. Patients and Methods: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p<0.05 was considered statistically significant. Results: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008). Conclusion: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation.

Targeted screening of multiple anti-inflammatory components from Chrysanthemi indici Flos by ligand fishing with affinity UF-LC/MS.

Chrysanthemi indic Flos (CIF) has been commonly consumed for the treatment of inflammation and related skin diseases. However, the potential bioactive components responsible for its anti-inflammatory and sensitive skin (SS) improvement activities, and the correlated mechanisms of action still remain unknown. In this work, it was firstly found that the CIF extract (CIFE) displayed arrestive free radical scavenging activity on DPPH and ABTS radicals, with no significant difference with positive control Trolox (p > 0.05). Then, compared to the negative group, CIFE markedly decreased the productions of the pro-inflammatory cytokines (IL-1ß, IL-6, PEG2, TNF-α, IFN-γ, NO) in LPS induced RAW264.7 cells in a dose-dependent manner (p < 0.01). Besides, CIFE strongly inhibited the COX-2 and hyaluronidase (HAase) with the IC50 values of 1.06 ± 0.01 µg/mL and 12.22 ± 0.39 µg/mL, indicating higher inhibitory effect than positive control of aspirin of 6.33 ± 0.05 µg/mL (p < 0.01), and comparable inhibitory effect with indometacin of 0.60 ± 0.03 µg/mL, and ascorbic acid of 11.03 ± 0.41 µg/mL (p > 0.05), respectively. Furthermore, kinetic assays with Lineweaver-Burk plot (Michaelis Menten equation) suggested that CIFE reversibly inhibited the COX-2 and HAase, with a mixed characteristics of competitive and non-competitive inhibition. Thereafter, multi-target affinity ultrafiltration liquid chromatography-mass spectrometry (UF-LC/MS) method was employed to fast fish out the potential COX-2 and HAase in CIFE. Herein, 13 components showed various affinity binding degrees to the COX-2 and HAase, while those components with relative binding affinity (RBA) value higher than 3.0, such as linarin and chlorogenic acid isomers, were deemed to be the most bioactive components for the anti-inflammatory and SS improvement activities of CIFE. Finally, the interaction mechanism, including binding energy, inhibition constant, docking sites, and the key amino acids involved in hydrogen bonds between the potential ligands and COX-2/HAase were simulated and confirmed with the molecule docking analysis. In summary, this study showcased the prominent anti-inflammatory and SS improvement activities of CIF, which would provide further insights on this functional medicinal plant to be a natural anti-SS remedy.

Association between childhood obesity and gut microbiota: 16S rRNA gene sequencing-based cohort study.

BACKGROUND: This study aimed to identify characteristic gut genera in obese and normal-weight children (8-12 years old) using 16S rDNA sequencing. The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity. Thirty normal-weight and thirty age- and sex-matched obese children were included. Questionnaires and body measurements were collected, and fecal samples underwent 16S rDNA sequencing. Significant differences in body mass index (BMI) and body-fat percentage were observed between the groups. Analysis of gut microbiota diversity revealed lower α-diversity in obese children. Di-fferences in gut microbiota composition were found between the two groups. Prevotella and Firmicutes were more abundant in the obese group, while Bacteroides and Sanguibacteroides were more prevalent in the control group. AIM: To identify the characteristic gut genera in obese and normal-weight children (8-12-year-old) using 16S rDNA sequencing, and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity. METHODS: Thirty each normal-weight, 1:1 matched for age and sex, and obese children, with an obese status from 2020 to 2022, were included in the control and obese groups, respectively. Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children. Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis. RESULTS: Significant differences in BMI and body-fat percentage were observed between the two groups. The Ace and Chao1 indices were significantly lower in the obese group than those in the control group, whereas differences were not significant in the Shannon and Simpson indices. Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children (P < 0.01), suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups. Prevotella, Firmicutes, Bacteroides, and Sanguibacteroides were more abundant in the obese and control groups, respectively. Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children. CONCLUSION: Obese children exhibited lower α-diversity in their gut microbiota than did the normal-weight children. Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

Reducing the risk of suicidal behaviors in medical graduate students: exploration of student-supervisor relationship and subjective family socioeconomic status.

Objective: This study aimed to investigate the association between the risk of suicidal behaviors and student-supervisor relationships and subjective family socioeconomic status (SFSS) in medical graduate students, and to propose preventive strategies to reduce the suicidal risk among medical graduate students. Materials and methods: A total of 1,310 validated questionnaires were collected from medical graduate students, which included demographic information, study programs, the Suicidal Behaviors Questionnaire-Revised (SBQ-R) questionnaire, the Leader-Member Exchange 7 (LMX-7) questionnaire, and SFSS by MacArthur Scale. Multiple regression analysis was employed to examine the associations between variables and adjust for confounders. A moderation analysis, containing simple slope analysis and Johnson-Neyman interval plots were used to analyze the moderating effect of the SFSS in the association of SBQ-R and LMX-7 scores. Results: A total of 88 participants (6.7%) were at risk of suicidal behaviors. In the high-quality student-supervisor relationship group (LMX-7 score ≥ 25), SFSS was significantly higher than in the low- and moderate-quality relationship group (p=0.002). The median SBQ-R score and proportion of suicide risk was significantly lower (p<0.001) in the high-quality student-supervisor relationship group. Multiple regression analysis indicated LMX-7 scores (ß=-0.098, 95% CI [-0.118, -0.077], p<0.001) and SFSS (ß=-0.073, 95% CI [-0.127, -0.019], p=0.008) were significantly negatively associated with SBQ-R, whereas the interaction term of SFSS with LMX-7 (ß=0.018, 95% CI [0.007, 0.029], p=0.001) showed a significant positive association with SBQ-R. The Johnson-Neyman interval showed a significant association between LMX-7 and SBQ-R scores only when SFSS was less than 7.82 (p<0.05). Conclusion: The risk of suicidal behaviors was associated with student-supervisor relationships and SFSS among medical graduate students. Poor relationships with supervisor were associated with an elevated risk of suicidality, and SFSS moderated this association. Educators should pay increased attention to the suicidal risk of medical graduate students with poor supervisor relationships, especially those from families with low SFSS, and provide timely preventive strategies.

Population Pharmacokinetics of Nirmatrelvir in Chinese Patients with COVID-19: Therapeutic Drug Monitoring and Dosing Regimen Selection in Clinical Practice.

OBJECTIVES: To establish a population pharmacokinetics (PopPK) model of nirmatrelvir in Chinese COVID-19 patients and provide reference for refining the dosing strategy of nirmatrelvir in patients confirmed to be infected with SARS-CoV-2. METHODS: A total of 80 blood samples were obtained from 35 mild moderate COVID-19 patients who were orally administered nirmatrelvir/ritonavir tablets. The PopPK model of nirmatrelvir was developed using a nonlinear mixed effects modeling approach. The stability and prediction of the final model were assessed through a combination of goodness-of-fit and bootstrap method. The exposure of nirmatrelvir across various clinical scenarios was simulated using Monte Carlo simulations. RESULTS: The pharmacokinetics of nirmatrelvir were well characterized by a one-compartment model with first-order absorption, and with creatinine clearance (Ccr) as the significant covariate. Typical population parameter estimates of apparent clearance and distribution volume for a patient with a Ccr of 95.5 mL·min-1were 3.45 L·h-1 and 48.71 L, respectively. The bootstrap and visual predictive check procedures demonstrated satisfactory predictive performance and robustness of the final model. CONCLUSION: The final model was capable of offering an early prediction of drug concentration ranges for different nirmatrelvir dosing regimens and optimize the dose regimen of nirmatrelvir in individuals with confirmed SARS-CoV-2 infection.

Structural Insight into the Binding Pattern and Interaction Mechanism of Antagonist MCC950 and Agonist BMS986299 with NLRP3 by Molecular Dynamics Simulation.

OBJECTIVE: The NLRP3 inflammasome mediates a range of inflammatory responses that are associated with an increasing number of pathological mechanisms. Over-activation of NLRP3 can exacerbate many diseases. However, NLRP3 antagonists have significant therapeutic potential. Moreover, NLRP3 plays an important role in limiting the growth and spread of some tumors, and NLRP3 agonists also have clinical value. MCC950 and BMS986299 are an antagonist and agonist of NLRP3, respectively. In light of the important clinical applications of NLRP3, especially for NLRP3 inhibitors, a computational method was used to investigate the interaction modes of MCC950 and BMS986299 with NLRP3 in order to design and develop more potent NLRP3 regulators. METHODS: In this study, the conformational behaviors of NLRP3 bound to the antagonist MCC950 in an inactive state and the agonist BMS986299 in an active state were investigated using 200 ns equilibrium all-atom molecular dynamics (MD) simulations, and then the analyses of the MD trajectories (RMSD, Rg, RMSF, SASA, PCA, and DCCM) were carried out to explore the mechanism of the antagonist and agonist on NLRP3 in the two different states. RESULTS: The RMSD, RMSF, Rg, SASA, and PCA analyses indicated that NLRP3 was more dispersive and less energetically stable in the active state than in the inactive state and that MCC950 significantly reduced the fluctuations of the interactive residues while BMS986299 did not. The antagonist MCC950 interacted with residues mainly in the NBD, HD1, WHD, and HD2 domains of NLRP3, whereas the agonist BMS986299 mainly in the NBD and WHD of NLRP3. Additionally, both compounds did not interact with residues located in the FISNA domain. The conformation of the FISNA domain appeared to change significantly when NLRP3 was translated from an inactive state to an active state. CONCLUSION: The antagonist may interact with residues mainly in the NBD, HD1, WHD, and HD2 domains, and the agonist may interact in the NBD and WHD domains. Our study provided new insights into the development of NLRP3 regulators.

Anxiety mediates association between sex and jaw function limitation in temporomandibular disorder patients from China.

Aim: The objective of this study is to explore the relationship between sex and jaw function and to test whether anxiety mediates the causal relationship between sex and jaw function in temporomandibular disorders (TMDs) patients. Methods: A total of 488 participants with TMD were included in the analysis. Demographic data were collected. Generalized anxiety symptoms and anxiety severity were initially assessed using the GAD-7 questionnaire. And jaw function limitation was measured using the JFLS-8 scale. A directed acyclic graph (DAG) was used in this study to evaluate the hypotheses. Mediation analysis was conducted to explore causality and to calculate the total effect, natural direct effect (NDE) and natural indirect effect (NIE). Results: In TMD patients, there was a significant association between female and jaw function (r = 0.17, p < 0.001), female and anxiety (r = 0.15, p = 0.002), anxiety and jaw function (r = 0.35, p < 0.001). In addition, sex can directly lead to differences in impaired jaw function (NDE: 3.719, 95% CI: 1.619-5.828, p < 0.001), and can also be causally related to jaw function through anxiety (NIE: 1.146, 95% CI: 0.267-2.024, p = 0.011). And the total effect was 4.865 (95% CI, 2.709-7.029, p < 0.001). Conclusion: A causal mechanism was found that anxiety acts as a mediator of sex effects on jaw function. Therefore, psychological factors need to be taken into account in the treatment of female TMD patients. Further clinical trials are needed to explore whether psychotherapy is more beneficial to improve jaw function in female TMD patients.

A first-principles study of the BC3N2 monolayer and a BC3N2/graphene heterostructure as promising anode materials for sodium-ion batteries.

High-performance sodium-ion batteries (SIBs) require anode materials with high capacity and fast kinetics. Based on first-principles calculations, we propose BC3N2 and BC3N2/graphene (B/G) heterostructure as potential SIB anode materials. The BC3N2 monolayer exhibits intrinsic metallic behavior. In addition, BC3N2 possesses a low Na+ diffusion barrier (0.15 eV), a high storage capacity (777 mA h g-1), a low open-circuit voltage (0.72 V), and a tiny axial expansion (0.36%). Compared with the BC3N2 monolayer, the B/G heterostructure exhibits a lower diffusion barrier of 0.027 eV, suggesting a much faster diffusion. More importantly, although the B/G heterostructure possesses heavier molar weight, its theoretical capacity (689 mA h g-1) is comparable to that of the BC3N2 monolayer. Based on the above-mentioned properties, we hope both the BC3N2 monolayer and the B/G heterostructure would be promising anodes for SIBs.

Heterogeneous associations between interleukin-6 receptor variants and phenotypes across ancestries and implications for therapy.

The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype-phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10-3), and higher white blood cell count (p-value for heterogeneity = 8.5 × 10-131). These data suggest a more salutary effect of IL6R blockade for T2D among individuals of AFR vs EUR ancestry and provide data to inform ongoing clinical trials targeting IL6 for an expanding number of conditions. Moreover, the method to test for heterogeneity of associations can be applied broadly to other large-scale genotype-phenotype screens in diverse populations.

Hierarchical Ti3C2/BiVO4 microcapsules for enhanced solar-driven water evaporation and photocatalytic H2 evolution.

Desalination processes frequently require a lot of energy to generate freshwater and energy, which depletes resources. Their reliance on each other creates tension between these two vital resources. Herein, hierarchical MXene nanosheets and bismuth vanadate (Ti3C2/BiVO4)-derived microcapsules were synthesized for a photothermal-induced photoredox reaction for twofold applications, namely, solar-driven water evaporation and hydrogen (H2) production. For this purpose, flexible aerogels were fabricated by introducing Ti3C2/BiVO4 microcapsules in the polymeric network of natural rubber latex (NRL-Ti3C2/BiVO4), and a high evaporation rate of 2.01 kg m-2 h-1 was achieved under 1-kW m-2 solar intensity. The excellent performance is attributed to the presence of Ti3C2/BiVO4 microcapsules in the polymeric network, which provides balanced hydrophilicity and broadband sun absorption (96 %) and is aimed at plasmonic heating with microscale thermal confinement tailored by heat transfer simulations. Notably, localized plasmonic heating at the catalyst active sites of the Ti3C2/BiVO4 heterostructure promotes enhanced photocatalytic H2 production evolved after 4 h of reaction is 9.39 µmol, which is highly efficient than pure BiVO4 and Ti3C2. This method turns the issue of water-fuel crisis into a collaborative connection, presenting avenues to collectively address the anticipated demand rather than fostering competition.

Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue.

The risk factors and causes of intracerebral hemorrhage (ICH) and the degree of functional recovery after ICH are distinct between young and elderly patients. The increasing incidence of ICH in young adults has become a concern; however, research on the molecules and pathways involved ICH in subjects of different ages is lacking. In this study, tandem mass tag (TMT)-based proteomics was utilized to examine the protein expression profiles of perihematomal tissue from young and aged mice 24 h after collagenase-induced ICH. Among the 5,129 quantified proteins, ICH induced 108 and 143 differentially expressed proteins (DEPs) in young and aged mice, respectively; specifically, there were 54 common DEPs, 54 unique DEPs in young mice and 89 unique DEPs in aged mice. In contrast, aging altered the expression of 58 proteins in the brain, resulting in 39 upregulated DEPs and 19 downregulated DEPs. Bioinformatics analysis indicated that ICH activated different proteins in complement pathways, coagulation cascades, the acute phase response, and the iron homeostasis signaling pathway in mice of both age groups. Protein-protein interaction (PPI) analysis and ingenuity pathway analysis (IPA) demonstrated that the unique DEPs in the young and aged mice were related to lipid metabolism and carbohydrate metabolism, respectively. Deeper paired-comparison analysis demonstrated that apolipoprotein M exhibited the most significant change in expression as a result of both aging and ICH. These results help illustrate age-related protein expression changes in the acute phase of ICH.

Pain symptoms are associated with two-point discrimination threshold in patients with temporomandibular disorders.

OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.

A novel data fusion based intelligent identification approach for working cycle stages of hydraulic excavators.

Accurately identifying the stage of the excavator working cycle is the prerequisite to achieve the staged energy-saving control. However, current identification methods often overlook the influence of hydraulic system latency on identification results and depend on a single model, resulting in poor generalization performance of the identification approaches. Moreover, expert calibration system remains a necessary factor for improving identification accuracy. Aiming at these issues, a hybrid multi-scale feature extractor and a decision-level data fusion classifier approach (HMSFE-DFC) is proposed to identify the working cycle stages of excavator. The input signal employs mixed signals from the main pump pressure and the control current of the proportional solenoid valve to reduce the response delay caused by the single main pump pressure signal. A hybrid multi-scale feature extractor is constructed using a convolutional neural network temporal self-attention feature extraction mechanism and one-dimensional ResNet-50 architecture to extract multiscale features. To prevent overfitting, a decision-level data fusion classifier is used to fuse the decisions information of numerous classifiers. The accuracy of stage identification for 10 consecutive working cycles reaches 95.21%, which verifies its effectiveness.

The dual effect of endoplasmic reticulum stress in digestive system tumors and intervention of Chinese botanical drug extracts: a review.

Endoplasmic reticulum (ER) homeostasis is essential for maintaining human health, and once imbalanced, it will trigger endoplasmic reticulum stress (ERS), which participates in the development of digestive system tumors and other diseases. ERS has dual effect on tumor cells, activating adaptive responses to promote survival or inducing apoptotic pathways to accelerate cell death of the tumor. Recent studies have demonstrated that Chinese botanical drug extracts can affect the tumor process of the digestive system by regulating ERS and exert anticancer effects. This article summarizes the dual effect of ERS in the process of digestive system tumors and the intervention of Chinese botanical drug extracts in recent years, as reference for the combined treatment of digestive system tumors with Chinese and modern medicine.

Application of LightGBM hybrid model based on TPE algorithm optimization in sleep apnea detection.

Introduction: Sleep apnoea syndrome (SAS) is a serious sleep disorder and early detection of sleep apnoea not only reduces treatment costs but also saves lives. Conventional polysomnography (PSG) is widely regarded as the gold standard diagnostic tool for sleep apnoea. However, this method is expensive, time-consuming and inherently disruptive to sleep. Recent studies have pointed out that ECG analysis is a simple and effective diagnostic method for sleep apnea, which can effectively provide physicians with an aid to diagnosis and reduce patients' suffering. Methods: To this end, in this paper proposes a LightGBM hybrid model based on ECG signals for efficient detection of sleep apnea. Firstly, the improved Isolated Forest algorithm is introduced to remove abnormal data and solve the data sample imbalance problem. Secondly, the parameters of LightGBM algorithm are optimised by the improved TPE (Tree-structured Parzen Estimator) algorithm to determine the best parameter configuration of the model. Finally, the fusion model TPE_OptGBM is used to detect sleep apnoea. In the experimental phase, we validated the model based on the sleep apnoea ECG database provided by Phillips-University of Marburg, Germany. Results: The experimental results show that the model proposed in this paper achieves an accuracy of 95.08%, a precision of 94.80%, a recall of 97.51%, and an F1 value of 96.14%. Discussion: All of these evaluation indicators are better than the current mainstream models, which is expected to assist the doctor's diagnostic process and provide a better medical experience for patients.

Research on Ocular Artifacts Removal from Single-Channel Electroencephalogram Signals in Obstructive Sleep Apnea Patients Based on Support Vector Machine, Improved Variational Mode Decomposition, and Second-Order Blind Identification.

The electroencephalogram (EEG) has recently emerged as a pivotal tool in brain imaging analysis, playing a crucial role in accurately interpreting brain functions and states. To address the problem that the presence of ocular artifacts in the EEG signals of patients with obstructive sleep apnea syndrome (OSAS) severely affects the accuracy of sleep staging recognition, we propose a method that integrates a support vector machine (SVM) with genetic algorithm (GA)-optimized variational mode decomposition (VMD) and second-order blind identification (SOBI) for the removal of ocular artifacts from single-channel EEG signals. The SVM is utilized to identify artifact-contaminated segments within preprocessed single-channel EEG signals. Subsequently, these signals are decomposed into variational modal components across different frequency bands using the GA-optimized VMD algorithm. These components undergo further decomposition via the SOBI algorithm, followed by the computation of their approximate entropy. An approximate entropy threshold is set to identify and remove components laden with ocular artifacts. Finally, the signal is reconstructed using the inverse SOBI and VMD algorithms. To validate the efficacy of our proposed method, we conducted experiments utilizing both simulated data and real OSAS sleep EEG data. The experimental results demonstrate that our algorithm not only effectively mitigates the presence of ocular artifacts but also minimizes EEG signal distortion, thereby enhancing the precision of sleep staging recognition based on the EEG signals of OSAS patients.

Design, Synthesis, Antitumor Activity Evaluation, and Molecular Dynamics Simulation of Some 2-Aminopyrazine Derivatives.

OBJECTIVE: Cancer poses a great threat to human health, and effective drugs to treat it are always needed. Several compounds containing a 2-aminopyrazine framework have been identified as antitumor agents with SHP2 inhibition activities. This current work aimed to search for more potent novel compounds possessing a 2-aminopyrazine moiety with antitumor activities. METHODS: A series of 12 novel 2-aminopyrazine derivatives was synthesized, and their structures were confirmed by spectroscopic techniques. The inhibitory activities of all the synthesized compounds against MDA-MB-231 and H1975 cancer cell lines were evaluated by an MTT assay. The most potent compound 3e was analyzed by flow cytometry. Subsequently, computational studies were performed to investigate the possible antitumor mechanisms of compound 3e. RESULTS: The results indicated that compound 3e exhibited potent antitumor activities with IC50 values of 11.84±0.83µM against H1975 cells and 5.66±2.39µM against MDA-MB-231 cells, which were more potent than the SHP2 inhibitor GS493 (IC50 = 19.08±1.01 µM against H1975 cells and IC50 = 25.02±1.47 µM against MDA-MB-231 cells). Further analysis by flow cytometry demonstrated that compound 3e induced cell apoptosis in H1975 cells. The results of the molecular docking and MD simulations, including RMSD, RMSF, PCA, DCCM and binding energy and decomposition analyses, revealed that compound 3e probably selectively inhibited SHP2. CONCLUSION: A new compound having a 2-aminopyrazine substructure with potent inhibitory activities against the H1975 and MDA-MB-231 cancer cells was obtained, meriting further investigation as an antitumor drug.