Multiple Transformation Matrix-Based Adaptive Projective Vortex Formation Tracking for Multiagent Systems With a Leader of Completely Unknown Input.

This article systematically studies projective vortex formation tracking (PVFT) of linear multiagent systems (MASs) on directed graphs through multiple transformation matrices, in which the input of leader and its upper bound information are not available to any follower. First, an innovative class of distributed adaptive observer is designed using the projection matrices to capture multiple desired virtual signals of the leader. Next, a novel kind of distributed PVFT protocol based on distributed observer, local observer and coordinates coupling matrices are proposed. Two different adaptive update mechanisms and nonlinear functions are introduced in the observer and controller to override the unknown input of the leader. Then, an algorithm is given, and the protocol under the algorithm is proved from three processes of estimation, aggregation, and rotation to enable linear systems to achieve PVFT. Finally, the effects of parameters on aggregation and rotation are analyzed systematically, and several simulation examples are given to illustrate the reliability of the results.

Predicting postoperative rehemorrhage in hypertensive intracerebral hemorrhage using noncontrast CT radiomics and clinical data with an interpretable machine learning approach.

In hypertensive intracerebral hemorrhage (HICH) patients, while emergency surgeries effectively reduce intracranial pressure and hematoma volume, their significant risk of causing postoperative rehemorrhage necessitates early detection and management to improve patient prognosis. This study sought to develop and validate machine learning (ML) models leveraging clinical data and noncontrast CT radiomics to pinpoint patients at risk of postoperative rehemorrhage, equipping clinicians with an early detection tool for prompt intervention. The study conducted a retrospective analysis on 609 HICH patients, dividing them into training and external verification cohorts. These patients were categorized into groups with and without postoperative rehemorrhage. Radiomics features from noncontrast CT images were extracted, standardized, and employed to create several ML models. These models underwent internal validation using both radiomics and clinical data, with the best model's feature significance assessed via the Shapley additive explanations (SHAP) method, then externally validated. In the study of 609 patients, postoperative rehemorrhage rates were similar in the training (18.8%, 80/426) and external verification (17.5%, 32/183) cohorts. Six significant noncontrast CT radiomics features were identified, with the support vector machine (SVM) model outperforming others in both internal and external validations. SHAP analysis highlighted five critical predictors of postoperative rehemorrhage risk, encompassing three radiomics features from noncontrast CT and two clinical data indicators. This study highlights the effectiveness of an SVM model combining radiomics features from noncontrast CT and clinical parameters in predicting postoperative rehemorrhage among HICH patients. This approach enables timely and effective interventions, thereby improving patient outcomes.

Clinicopathological and therapeutic analysis of PDGFRA mutated gastrointestinal stromal tumor.

BACKGROUND: Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) mutation has causes a rare subgroup of gastrointestinal stromal tumor (GIST) and not too much attention has been paid on it until the appearance of Avapritinib. This study aims to explore the clinicopathological features, therapy and prognosis of PDGFRA-mutant GIST for better understanding and clinical practice. METHOD: 119 PDGFRA-mutant GIST patients were retrospectively collected from 2038 patients who underwent genetic testing. Kaplan-Meier method was used. RESULTS: The incidence rate of PDGFRA-mutant GIST in our center was 5.8 %, with 79 males, 40 females, and a median age of 57 (25⁃80) years old. All the tumors were in the stomach, among which 60 were epithelioid type, 25 were spindle type and 34 were mixed type. There were 13 cases of exon 12 mutation and 106 cases of exon 18 mutation including 83 cases of D842V mutation (69.7 %). During a median follow⁃up of 49.6 (range, 1⁃154) months, progression could be observed in 12 patients with gene mutation at the codon 842 of exon 18, another case was V561D mutation in exon 12. The 5-year diseases⁃free survival (DFS) was 90.1 %, which was associated with the loss of CD34 expression (P＜0.001). Patients in D842V group showed a marginal worse prognosis than those in non-D842V group (P = 0.163). According to the NIH criteria, high risk group showed a poorer prognosis than non-high risk group (P = 0.003), however, there were no significant differences among the three non-high risk groups (P = 0.495, P = 0.652). Among 13 advanced patients, 5 cases (treated with Avapritinib) achieved partial remission. CONCLUSION: PDGFRA-mutant GIST mostly derived from stomach, with a relative indolent behavior. D842V mutation and lose of CD34 expression were adverse prognostic factors. Avapritinib can effectively control advanced patients in a certain period of time.

Folic acid (FA)-conjugated mesoporous silica nanoparticles combined with MRP-1 siRNA improves the suppressive effects of myricetin on non-small cell lung cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is a common diagnosed cancer disease worldwide and its management remains a challenge. Synergistic cancer therapeutic strategy is interesting for multiple advantages, such as excellent targeting accuracy, low side effects, and promoted therapeutic efficiency. In the present study, myricetin (Myr)-loaded mesoporous silica nanoparticles (MSN) combined with multidrug resistance protein (MRP-1) siRNA was prepared. The surface of the synthesized nanoparticles was modified with folic acid (FA) to promote the therapeutic efficiency of Myr for the treatment of NSCLC. The collected particles were nano-sized and showed a sustained release of Myr in the physiological conditions. FA-conjugated nanoformulations displayed a significant uptake in lung cancer cells compared with that of the non-targeted nanoparticles. The in vitro drug release results suggested a sustained release in FA-conjugated MSN with Myr and MRP-1 nanoparticles compared to the free Myr and MSN combined with MRP-1/Myr. Treatments with FA-conjugated MSN combined with Myr and MRP-1 markedly reduced the cell viability of lung cancer cell lines, including A549 and NCI-H1299, which was accompanied with the decreased number of colony formation. In addition, FA-conjugated MSN loaded with Myr and MRP-1 significantly induced apoptosis in lung cancer cells, along with up-regulated expression levels of cleaved Caspase-3 and PARP. In vivo fluorescence results demonstrated that FA-conjugated MSN with Myr and MRP-1 nanoparticles could specifically accumulate at tumor sites. Compared with free Myr and MSN combined with MRP-1/Myr nanoparticles, FA-conjugated MSN loaded with Myr and MRP-1 nanoparticles could more effectively suppress tumor growth with little side effects. Overall, FA-conjugated nanoparticulate system could provide a novel and effective platform for the treatment of NSCLC.

MiR-216b suppresses cell proliferation, migration, invasion, and epithelial-mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer.

Background/aims: MiR-216b and forkhead box M1 (FOXM1) were demonstrated to exert their biological effects on the development and progression of tumors. This study aimed to investigate the expression and role of miR-216b and FOXM1 in tissues and cell lines of non-small cell lung cancer (NSCLC). Methods: The expressions of miR-216b and FOXM1 in NSCLC tissues and cells were detected by qRT-PCR and Western blot analysis. Cell proliferation was measured by CCK-8 assay. Cell migration and invasion were confirmed by Transwell assay. Finally, the bioinformatics and dual-luciferase reporter assay were conducted to validate the relationship of miR-216b and FOXM1. Results: Compared with normal tissues and cells, the expression of miR-216b was obviously decreased in NSCLC tissues and cells. However, the expressions of FOXM1 mRNA and protein were significantly increased, and negatively correlated with the expression of miR-216b. Multivariate Cox's regression analysis suggested that miR-216b or FOXM1 expression was an independent prognostic factor for patients with NSCLC. MiR-216b overexpression remarkably repressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells. The bioinformatics and dual-luciferase reporter assay validated that the 3'-untranslated region (3'-UTR) of FOXM1 mRNA was indeed a direct target of FOXM1. In vitro, overexpression of FOXM1 partially eliminated inhibitory effects of miR-216b on cell proliferation, migration, and invasion, whereas inhibition of FOXM1 contributed to inhibitory effects mediated by miR-216b. Conclusion: MiR-216b inhibits cell proliferation, migration, invasion, and EMT by targeting the expression of FOXM1 in human NSCLC. These findings suggested a potential therapeutic role of miR-216b in patients of NSCLC.

Endophilin A1 Promotes Actin Polymerization in Dendritic Spines Required for Synaptic Potentiation.

Endophilin A1 is a member of the N-BAR domain-containing endophilin A protein family that is involved in membrane dynamics and trafficking. At the presynaptic terminal, endophilin As participate in synaptic vesicle recycling and autophagosome formation. By gene knockout studies, here we report that postsynaptic endophilin A1 functions in synaptic plasticity. Ablation of endophilin A1 in the hippocampal CA1 region of mature mouse brain impairs long-term spatial and contextual fear memory. Its loss in CA1 neurons postsynaptic of the Schaffer collateral pathway causes impairment in their AMPA-type glutamate receptor-mediated synaptic transmission and long-term potentiation. In KO neurons, defects in the structural and functional plasticity of dendritic spines can be rescued by overexpression of endophilin A1 but not A2 or A3. Further, endophilin A1 promotes actin polymerization in dendritic spines during synaptic potentiation. These findings reveal a physiological role of endophilin A1 distinct from that of other endophilin As at the postsynaptic site.

[Establishment of Reference Value of Hs-cTnT in Sichuan Region and Its Diagnostic Value in Patients with Chest Pain].

OBJECTIVE: To establish the reference value of high sensitive cardiac troponin T (hs-cTnT) and the efficiency of reference value in the diagnosis of chest pain. METHODS: Volunteers from eight independent communities in Chengdu,Sichuan were selected with detailed records of physical examination,electrocardiogram,ultrasound examination. The level of hs-cTnT for healthy volunteers was tested to determine ninety-ninth percentile references according to sex and ages. 2 249 patients with chest pain in the emergency department of Western China Hospital from July 2009 to July 2014 were enrolled to measure the efficiency of reference value for diagnosing acute myocardial infarction (AMI). RESULTS: There were 1 305 volunteers included finally. Among them,the mean hs-cTnT level of male was 4.3 (3.2-5.9) ng/L,which was significantly higher than that of female 3.0 (3.0-3.1) ng/L ( P<0.01) . The correlation coefficient between age and hs-cTnT level was 0.43 (male) and 0.29 (female),and the P-value was less than 0.01. The 99th percentile values of male were 10.8 ng/L,15.4 ng/L and 19.7 ng/L for <45 yr.,45-<60 yr. and ≥60 yr.,respectively. Those values of female were 4.6 ng/L,8.9 ng/L,18.8 ng/L,respectively. There was no difference in sensitivity and specificity between the value we figured out and manufactures provided (14.0 ng/L) for those<60 yr.. For the patients ≥60 yr.,the sensitivity and negative predictive value did not show diversity ( P>0.05) but the specificity and positive predictive value showed significant difference (male: 0.67 vs. 0.56 and 0.83 vs. 0.79, P<0.05;female:0.75 vs. 0.68 and 0.74 vs. 0.69, P<0.05). CONCLUSION: We recommends that the ninety-ninth percentile reference value of patients<60 yr. should be 14.0 ng/L,while 20.0 ng/L for those patients≥60 yr.

Effect of subarachnoid nerve block anesthesia on glutamate transporter GLAST and GLT-1 expressions in rabbits.

OBJECTIVE: To observe the effect of subarachnoid nerve block anesthesia on glutamate transporter glutamate-aspartate transporter (GLAST) and GLT-1 expressions in rabbits, and to investigate the effect of peripheral nerve anesthesia on the morphology and function of the spinal cord. METHODS: Twenty healthy New Zealand white rabbits were randomly divided into two groups: the experimental group and control group; with 10 rabbits in each group. For spinal nerve anesthesia, 5 g/L of bupivacaine was used in the experimental group, and sterile saline was used in the control group. After 30 min of cardiac perfusion, GLAST and GLT-1 protein expression in spinal neurons were detected by immunohistochemistry and immunofluorescence staining. RESULTS: GLAST and GLT-1 protein-positive cells increased in neurons in the experimental group, compared with the control group (P < 0.05). CONCLUSIONS: After subarachnoid nerve block anesthesia, rabbit glutamate transporter GLAST and GLT-1 expression is increased; and spinal cord nerve cell function is inhibited.

Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap.

Dendritic spines are actin-rich membrane protrusions that are the major sites of excitatory synaptic input in the mammalian brain, and their morphological plasticity provides structural basis for learning and memory. Here we report that endophilin A1, with a well-established role in clathrin-mediated synaptic vesicle endocytosis at the presynaptic terminal, also localizes to dendritic spines and is required for spine morphogenesis, synapse formation and synaptic function. We identify p140Cap, a regulator of cytoskeleton reorganization, as a downstream effector of endophilin A1 and demonstrate that disruption of their interaction impairs spine formation and maturation. Moreover, we demonstrate that knockdown of endophilin A1 or p140Cap impairs spine stabilization and synaptic function. We further show that endophilin A1 regulates the distribution of p140Cap and its downstream effector, the F-actin-binding protein cortactin as well as F-actin enrichment in dendritic spines. Together, these results reveal a novel function of postsynaptic endophilin A1 in spine morphogenesis, stabilization and synaptic function through the regulation of p140Cap.

Diagnosis of acute myocardial infarction in patients with renal insufficiency using high-sensitivity troponin T.

BACKGROUND: The objective of this study was to examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) for acute myocardial infarction (AMI) in patients with renal insufficiency, since this population has a high incidence of non-AMI elevations of hs-cTnT. METHODS: In this prospective study, we enrolled 2249 consecutive patients presenting with chest pain in the emergency department (ED), of whom 19.5% had an estimated glomerular filtration rate (eGFR)cys of <60 mL·min-1 (1.73 m2)-1. Hs-cTnT levels were measured blindly at presentation. RESULTS: Of the patients, 1108 (49.3%) were diagnosed as having AMI [321 with non-ST segment elevation myocardial infarction (NSTEMI)]. In patients whose final diagnosis was not AMI, there was a low but significant correlation between hs-cTnT and renal function [eGFRcys, r=-0.43 (-0.48, -0.38), p<0.001; eGFRcreat, r=-0.33 (-0.38, -0.27), p<0.001]. The area under the curve of the receiver operating characteristic (AUC) for hs-cTnT to diagnose AMI was 0.93 in patients with eGFRcys levels of <30 mL·min-1 (1.73 m2)-1, and AUCs did not vary significantly according to eGFR categories. On the basis of the ROC curve, the optimal threshold value for hs-cTnT was 143.6 ng·L-1 to diagnose AMI in patients with eGFRcys of <30 mL·min-1 (1.73 m2)-1, with a sensitivity of 83% and a specificity of 91%; 54.1 ng·L-1 in patients with eGFRcys between 30 and 59 mL·min-1, with a sensitivity of 90% and a specificity of 87%; 30.0 ng·L-1 in patients with eGFRcys between 60 and 89 mL·min-1, with a sensitivity of 89% and a specificity of 85%; and 20.3 ng·L-1 in patients with eGFRcys ≥90 mL·min-1 (1.73 m2)-1, with a sensitivity of 92% and a specificity of 88%. The same observations were done for the diagnosis of NSTEMI. CONCLUSIONS: Using a higher hs-cTnT cut-off value based on eGFR level is necessary for accurate diagnosis of AMI or NSTEMI in patients with renal insufficiency.

Thermo-regulated phase separable catalysis (TPSC)-based atom transfer radical polymerization in a thermo-regulated ionic liquid.

A thermo-regulated phase separable catalysis (TPSC) system for AGET ATRP based on a thermo-regulated ionic liquid was developed for the first time. The corresponding transition metal catalysts could be easily recovered and reused several times with negligible loss of catalytic activity.