TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are important candidate seed cells for periodontal tissue engineering, but the presence of lipopolysaccharide(LPS) in periodontal tissues inhibits the self-renewal and osteogenic differentiation of hPDLSCs. Our previous studies demonstrated that TAZ is a positive regulator of osteogenic differentiation of hPDLSCs, but whether TAZ can protect hPDLSCs from LPS is still unknown. The present study aimed to explore the regulatory effect of TAZ on the osteogenic differentiation of hPDLSCs in an LPS-induced inflammatory model, and to preliminarily reveal the molecular mechanisms related to the NF-κB signaling pathway. METHODS: LPS was added to the culture medium of hPDLSCs. The influence of LPS on hPDLSC proliferation was analyzed by CCK-8 assays. The effects of LPS on hPDLSC osteogenic differentiation were detected by Alizarin Red staining, ALP staining, Western Blot and qRT-PCR analysis of osteogenesis-related genes. The effects of LPS on the osteogenic differentiation of hPDLSCs with TAZ overexpressed or knocked down via lentivirus were analyzed. NF-κB signaling in hPDLSCs was analyzed by Western Blot and immunofluorescence. RESULTS: LPS inhibited the osteogenic differentiation of hPDLSCs, inhibited TAZ expression, and activated the NF-κB signaling pathway. Overexpressing TAZ in hPDLSCs partly reversed the negative effects of LPS on osteogenic differentiation and inhibited the activation of the NF-κB pathway by LPS. TAZ knockdown enhanced the inhibitory effects of LPS on osteogenesis. CONCLUSION: Overexpressing TAZ could partly reverse the inhibitory effects of LPS on the osteogenic differentiation of hPDLSCs, possibly through inhibiting the NF-κB signaling pathway. TAZ is a potential target for improving hPDLSC-based periodontal tissue regeneration in inflammatory environments.

Titanium dioxide-supported mercury photocatalysts for oxidative removal of hydrogen sulfide from the air using a portable air purification unit.

Photocatalytic removal of gaseous hydrogen sulfide (H2S) has been studied through the control of key process variables using a prototype air purifier (AP) fabricated with titanium dioxide (TiO2)-supported mercury. The performance of Hg/TiO2 systems, prepared with different Hg mass proportions over TiO2 (such as 0.1%, 1%, 2%, and 5%), is measured against 5 ppm H2S at 160 L min-1 under UV irradiation. Accordingly, their removal efficiency (RE) values after 360 s are 40.3%, 74.8%, 99.3%, and 99.9%, respectively (relative to 33.5% of AP (TiO2)). An AP with a 2% Hg/TiO2 unit achieves a clean air delivery rate of 32 L min-1 with kinetic reaction rate (r (at 10% RE)) of 0.774 mmol h-1 g-1, quantum yield of 2.19E-02 molecules photon-1, and space-time yield of 1.46E-04 molecules photon-1 mg-1. The superior photocatalytic performance of Hg/TiO2 is supported by superoxide anion and hydroxyl radicals formed in dry air and humid nitrogen (N2) environments, respectively. A density functional theory simulation suggests that the presence of oxygen vacancies should promote the disparities in the electronic structure to subsequently affect the reaction pathways and energetics. The presence of moisture enhances the robust formation of a mercury-OH bond to favorably yield ß-mercury sulfide from H2S.

EID3 inhibits the osteogenic differentiation of periodontal ligament stem cells and mediates the signal transduction of TAZ-EID3-AKT/MTOR/ERK.

Exploring the molecular mechanisms of cell behaviors is beneficial for promoting periodontal ligament stem cell (PDLSC)-mediated tissue regeneration. This study intends to explore the regulatory effects of EID3 on cell proliferation, apoptosis, and osteogenic differentiation and to preliminarily explore the regulatory mechanism of EID3. Here, EID3 was overexpressed or knocked down in PDLSCs by recombinant lentivirus. Then, cell proliferation activity was analyzed by colony-forming assay, EdU assay, and cell cycle assay. Cell apoptosis was detected by flow cytometry. The osteo-differentiation potential was analyzed using ALP activity assay, ALP staining, alizarin red staining, and mRNA and protein assay of osteo-differentiation related genes. The results showed that when EID3 was knocked down, the proliferation activity and osteogenic differentiation potential of PDLSCs decreased, while they increased when EID3 was overexpressed. The cell apoptosis rate decreased in PDLSCs with EID3 knockdown but increased in PDLSCs with EID3 overexpression. Moreover, EID3 inhibited the transduction of the AKT/MTOR and ERK signaling pathway. In addition, TAZ negatively regulated the expression of EID3, and the overexpression of EID3 partially reversed the promotive effects of TAZ on the osteogenic differentiation of PDLSCs. Taken together, EID3 inhibits the proliferation and osteogenic differentiation while promoting the apoptosis of PDLSCs. EID3 inhibits the transduction of the AKT/MTOR and ERK signaling pathways and mediates the regulatory effect of TAZ on PDLSC osteogenic differentiation.

Clinical study of two-dimensional speckle tracking to evaluate abnormal myocardial motion due to coronary lesions.

OBJECTIVE: To investigate the predictive ability of global longitudinal strain (GLS) and mechanical dispersion for coronary stenosis and provide a more reliable noninvasive method for diagnosis of obstructive coronary artery disease(OCAD). METHODS: Sixty-seven patients diagnosed with suspected CAD were included in the study. Patients with coronary stenosis greater than 50% were assigned as OCAD, while the others were assigned as non obstructive coronary artery disease(NOCAD). General information was collected and patients underwent speckle tracking echocardiogram(STE). RESULTS: Spearman's correlation analysis showed that GLS and mechanical dispersion were positively correlated with the degree of coronary stenosis (r = 0.383, 0.342, p < 0.05), and there was also a positive correlation between GLS and mechanical dispersion (r = 0.327, p < 0.05). GLS, longitudinal strain (LS) of each chamber, and mechanical dispersion were higher in the OCAD group than in the NOCAD group (p < 0.05). Univariate regression analysis showed that GLS, each lumen LS and mechanical dispersion were statistically significant (p < 0.05). Multifactorial regression analysis showed that elevated GLS (p = 0.007) and elevated mechanical dispersion (p = 0.030) were independent risk factors for OCAD. The ROC curves showed that GLS predicted OCAD (AUC area 0.745, 95% CI 0.624 to 0.865) versus mechanical discrete prediction of OCAD (AUC area 0.702, 95% CI 0.569 to 0.834) were more diagnostic than conventional cardiac ultrasound observations of ventricular wall motion abnormalities (AUC area 0.566, 95% CI 0.463 to 0.669). CONCLUSIONS: Combining GLS with mechanical dispersion can rapidly assess OCAD in a very short period, which has strong promotion value and in-depth research value.

Impacts of different culture times on pregnancy outcomes after thawing of cleavage stage embryos.

OBJECTIVE: This study assessed the impacts of in vitro culture times of cleavage embryos on clinical pregnancy outcomes. METHODS: This retrospective cohort study was performed at the Reproductive Medicine Department of Hainan Modern Women and Children's Hospital in China between January 2018 and December 2022. Patients who first underwent frozen embryo transfer with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles on day 3 were included. According to the time of embryo culture after thawing, the embryos were divided into long-term culture group(18-20 h) and short-term culture group (2-4 h). The clinical pregnancy rate was regarded as he primary outcome. To minimize confounding factors and reduce selection bias, the propensity score matching was used to balance the effects of known confounding factors and to reduce selection bias. Stratified analyses and multiple logistic regression analyses were used to evaluate the risk factors affecting the clinical pregnancy outcomes after matching. RESULTS: General characteristics between two groups were comparable after matching. In the long-term culture group, 266/381 (69.81%) embryos had more than 10 blastomeres, and 75/381 (19.68%) reached the morula stage. After overnight culture, the implantation rate (27.97% vs. 14.28%, P = 0.018) and clinical pregnancy rate (38.46% vs. 22.5%, P = 0.05) were increased in the group with proliferating blastomeres. The long-term culture group trended to have a higher clinical pregnancy rate compared with the short-term culture group (35.74% vs. 29.79%). No statistical differences in clinical pregnancy outcomes between the two groups were observed after matching, including the rates of implantation (25.46% vs23.98%), miscarriages (25% vs. 22.85%), ongoing pregnancy rate (76.2% vs. 77.15%) and live birth rate (26.8% vs. 22.98%). Stratified analyses were performed according to the age of the patients. After matching, there were no significant differences in the clinical pregnancy, implantation and miscarriage rates between the two groups for patients > 35 or ≤ 35 years of age. Subgroup analyses were performed according to the quality of the transferred embryos. There were no significant differences in the clinical outcomes, between two groups after embryos transferred with the same quality. Multivariate Logistic regression analysis was used to evaluate the influencing factors of clinical pregnancy outcomes after matching. Culture time was not found to be an independent predictor for clinical pregnancy [OR 0.742, 95%CI 0.487 ~ 1.13; P = 0.165]. The age of oocyte retrieval [OR 0.906, 95%CI 0.865 ~ 0.949; P <0.001] and the number of high-quality embryos transferred [OR 1.787, 95%CI 1.256 ~ 2.543; P = 0.001] were independent factors affecting clinical pregnancy outcomes. CONCLUSIONS: In vitro 18-20 h culture of embryos with either good-or non-good-quality will not adversely affect the clinical pregnancy.

Dasatinib regulates the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals.

Periodontal ligament stem cells (PDLSCs) are important candidate seed cells for alveolar bone tissue engineering. Dasatinib is a tyrosine kinase inhibitor, and its influence on the osteogenic differentiation of mesenchymal stem cells is a controversial topic. The present study explored the effects of different concentrations of dasatinib on the proliferation and osteogenic differentiation of PDLSCs and tentatively revealed the related mechanism. The results of CCK8 showed that low concentrations of dasatinib (1 nM) did not affect proliferation, while high concentrations of dasatinib significantly inhibited the proliferative activity of PDLSCs. This could be related to the inhibiting effects of dasatinib on Erk signals. ALP staining, alizarin red staining, and western blot proved that low concentrations of dasatinib (1 nM) promoted the osteogenic differentiation of PDLSCs, while high concentrations of dasatinib inhibited it. The negative effects of dasatinib on osteogenic differentiation were reversed when EID3 was knocked down, suggesting that EID3 mediates the regulation of dasatinib on the osteo-differentiation of PDLSCs. Taken together, high concentrations of dasatinib inhibited the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals, while low concentrations of dasatinib could be a potential method to enhance the bone regeneration ability of PDLSCs.

Application of machine learning to predict the occurrence of arrhythmia after acute myocardial infarction.

BACKGROUND: Early identification of the occurrence of arrhythmia in patients with acute myocardial infarction plays an essential role in clinical decision-making. The present study attempted to use machine learning (ML) methods to build predictive models of arrhythmia after acute myocardial infarction (AMI). METHODS: A total of 2084 patients with acute myocardial infarction were enrolled in this study. (All data is available on Github: https://github.com/wangsuhuai/AMI-database1.git) . The primary outcome is whether tachyarrhythmia occurred during admission containing atrial arrhythmia, ventricular arrhythmia, and supraventricular tachycardia. All data is randomly divided into a training set (80%) and an internal testing set (20%). Apply three machine learning algorithms: decision tree, random forest (RF), and artificial neural network (ANN) to learn the training set to build a model, then use the testing set to evaluate the prediction performance, and compare it with the model built by the Global Registry of Acute Coronary Events (GRACE) risk variable set. RESULTS: Three ML models predict the occurrence of tachyarrhythmias after AMI. After variable selection, the artificial neural network (ANN) model has reached the highest accuracy rate, which is better than the model constructed using the Grace variable set. After applying SHapley Additive exPlanations (SHAP) to make the model interpretable, the most important features are abnormal wall motion, lesion location, bundle branch block, age, and heart rate. Among them, RBBB (odds ratio [OR]: 4.21; 95% confidence interval [CI]: 2.42-7.02), ≥ 2 ventricular walls motion abnormal (OR: 3.26; 95% CI: 2.01-4.36) and right coronary artery occlusion (OR: 3.00; 95% CI: 1.98-4.56) are significant factors related to arrhythmia after AMI. CONCLUSIONS: We used advanced machine learning methods to build prediction models for tachyarrhythmia after AMI for the first time (especially the ANN model that has the best performance). The current study can supplement the current AMI risk score, provide a reliable evaluation method for the clinic, and broaden the new horizons of ML and clinical research. Trial registration Clinical Trial Registry No.: ChiCTR2100041960.

Effects of ACEI and ARB on COVID-19 patients: A meta-analysis.

BACKGROUND: The clinical use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in patients with COVID-19 infection remains controversial. Therefore, we performed a meta-analysis on the effects of ACEI/ARB on disease symptoms and laboratory tests in hypertensive patients infected with COVID-19 virus and those who did not use ACEI/ARB. METHODS: We systematically searched the relevant literatures from Pubmed, Embase, EuropePMC, CNKI, and other databases during the study period of 31 December 2019 (solstice, 15 March 2020), and analyzed the differences in symptoms and laboratory tests between patients with COVID-19 and hypertension who used ACEI/ARB drugs and those who did not. All statistical analyses were performed with REVMAN5.3. RESULTS: We included a total of 1808 patients with hypertension diagnosed with COVID-19 in six studies. Analysis results show that ACEI/ARB drugs group D-dimer is lower (SMD = -0.22, 95%CI: -0.36 to -0.06), and the chances of getting fever is lower (OR = 0.74, 95%CI: 0.55 to 0.98). Meanwhile, laboratory data and symptoms were not statistical difference, but creatinine tends to rise (SMD = 0.22, 95% CI: 0.04 to 0.41). CONCLUSION: We found that the administration of ACEI/ARB drugs had positive effect on reducing D-dimer and the number of people with fever. Meanwhile it had no significant effect on other laboratory tests (creatinine excepted) or symptoms in patients with COVID-19, while special attention was still needed in patients with renal insufficiency.

Clinical characteristics of COVID-19 with cardiac injury: a systematic review and meta-analysis.

OBJECTIVES: Cardiac injury is associated with poor prognosis of 2019 novel coronavirus disease 2019 (COVID-19), but the risk factors for cardiac injury have not been fully studied. In this study, we carried out a systematic analysis of clinical characteristics in COVID-19 patients to determine potential risk factors for cardiac injury complicated COVID-19 virus infection. METHODS: We systematically searched relevant literature published in Pubmed, Embase, Europe PMC, CNKI and other databases. All statistical analyses were performed using STATA 16.0. RESULTS: We analysed 5726 confirmed cases from 17 studies. The results indicated that compared with non-cardiac-injured patients, patients with cardiac injury are older, with a greater proportion of male patients, with higher possibilities of existing comorbidities, with higher risks of clinical complications, need for mechanical ventilation, ICU transfer and mortality. Moreover, C-reactive protein, procalcitonin, D-dimer, NT-proBNP and blood creatinine in patients with cardiac injury are also higher while lymphocyte counts and platelet counts decreased. However, we fortuitously found that patients with cardiac injury did not present higher clinical specificity for chest distress (P = 0.304), chest pain (P = 0.334), palpitations (P = 0.793) and smoking (P = 0.234). Similarly, the risk of concomitant arrhythmia (P = 0.103) did not increase observably either. CONCLUSION: Age, male gender and comorbidities are risk factors for cardiac injury complicated COVID-19 infection. Such patients are susceptible to complications and usually have abnormal results of laboratory tests, leading to poor outcomes. Contrary to common cardiac diseases, cardiac injury complicated COVID-19 infection did not significantly induce chest distress, chest pain, palpitations or arrhythmias. Our study indicates that early prevention should be applied to COVID-19 patients with cardiac injury to reduce adverse outcomes.

Fabrication of Densely Packed AlN Nanowires by a Chemical Conversion of Al(2)O(3) Nanowires Based on Porous Anodic Alumina Film.

Porous alumina film on aluminum with gel-like pore wall was prepared by a two-step anodization of aluminum, and the corresponding gel-like porous film was etched in diluted NaOH solution to produce alumina nanowires in the form of densely packed alignment. The resultant alumina nanowires were reacted with NH(3) and evaporated aluminum at an elevated temperature to be converted into densely packed aluminum nitride (AlN) nanowires. The AlN nanowires have a diameter of 15-20 nm larger than that of the alumina nanowires due to the supplement of the additional evaporated aluminum. The results suggest that it might be possible to prepare other aluminum compound nanowires through similar process.