Enhancing root physiology for increased yield in water-saving and drought-resistance rice with optimal irrigation and nitrogen.

Objectives: Water-saving and drought-resistance rice (WDR) plays a vital role in the sustainable development of agriculture. Nevertheless, the impacts and processes of water and nitrogen on grain yield in WDR remain unclear. Methods: In this study, Hanyou 73 (WDR) and Hyou 518 (rice) were used as materials. Three kinds of nitrogen fertilizer application rate (NFAR) were set in the pot experiment, including no NFAR (nitrogen as urea applied at 0 g/pot), medium NFAR (nitrogen as urea applied at 15.6 g/pot), and high NFAR (nitrogen as urea applied at 31.2 g/pot). Two irrigation regimes, continuous flooding cultivation and water stress, were set under each NFAR. The relationships between root and shoot morphophysiology and grain yield in WDR were explored. Results: The results demonstrated the following: 1) under the same irrigation regime, the grain yield of two varieties increased with the increase of NFAR. Under the same NFAR, the reduction of irrigation amount significantly reduced the grain yield in Hyou 518 (7.1%-15.1%) but had no substantial influence on the grain yield in Hanyou 73. 2) Under the same irrigation regime, increasing the NFAR could improve the root morphophysiology (root dry weight, root oxidation activity, root bleeding rate, root total absorbing surface area, root active absorbing surface area, and zeatin + zeatin riboside contents in roots) and aboveground physiological indexes (leaf photosynthetic rate, non-structural carbohydrate accumulation in stems, and nitrate reductase activity in leaves) in two varieties. Under the same NFAR, increasing the irrigation amount could significantly increase the above indexes in Hyou 518 (except root dry weight) but has little effect on Hanyou 73. 3) Analysis of correlations revealed that the grain yield of Hyou 518 and Hanyou 73 was basically positively correlated with aboveground physiology and root morphophysiology, respectively. Conclusion: The grain yield could be maintained by water stress under medium NFAR in WDR. The improvement of root morphophysiology is a major factor for high yield under the irrigation regime and NFAR treatments in WDR.

Risk stratification and predictive modeling of postoperative delirium in chronic subdural hematoma.

Background- Postoperative delirium is a common complication associated with the elderly, causing increased morbidity and prolonged hospital stay. However, its risk factors in chronic subdural hematoma patients have not been well studied. Methods- A total of 202 consecutive patients with chronic subdural hematoma at Peking University Third Hospital between January 2018 and January 2023 were enrolled. Various clinical indicators were analyzed to identify independent risk factors for postoperative delirium using univariate and multivariate regression analyses. Delirium risk prediction models were developed as a nomogram and a Markov chain. Results- Out of the 202 patients (age, 71 (IQR, 18); female-to-male ratio, 1:2.7) studied, 63 (31.2%) experienced postoperative delirium. Univariate analysis identified age (p < 0.001), gender (p = 0.014), restraint belt use (p < 0.001), electrolyte imbalance (p < 0.001), visual analog scale score (p < 0.001), hematoma thickness (p < 0.001), midline shift (p < 0.001), hematoma side (p = 0.013), hematoma location (p = 0.018), and urinal catheterization (p = 0.028) as significant factors. Multivariate regression analysis confirmed the significance of restraint belt use (B = 7.657, p < 0.001), electrolyte imbalance (B = -3.993, p = 0.001), visual analog scale score (B = 2.331, p = 0.016), and midline shift (B = 0.335, p = 0.007). Hematoma thickness and age had no significant impact. Conclusion- Increased midline shift and visual analog scale scores, alongside restraint belt use and electrolyte imbalance elevate delirium risk in chronic subdural hematoma surgery. Our prediction models may offer reference value in this context.

From glioma gloom to immune bloom: unveiling novel immunotherapeutic paradigms-a review.

In tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.

Analysis of pre-crash scenarios and contributing factors for autonomous vehicle crashes at intersections.

Intersections are high-risk locations for autonomous vehicles (AVs). Crash causation analysis based on pre-crash scenarios can provide new insight into these crashes that can lead to effective countermeasures, but there are significant differences in pre-crash scenarios between autonomous and conventional vehicles, and inadequate AV data has put limits on research. The association rule method, however, can yield useful results despite these limits. This study therefore aims to use the method with pre-crash scenarios to understand the characteristics and contributing factors of AV crashes at intersections from the latest 5-year AV crash data. Analysis of 197 AV crashes at intersections revealed 30 types of pre-crash scenarios. The rear-end crash (58.88%) and lane change crash (16.24%) were the most frequently occurring scenarios for AVs. The proportion of AVs being rear-ended by conventional vehicles was 58.38%. The main contributing factors of these two most common AV scenarios were identified by association rules and crash causes were analyzed from the perspective of AV decision-making. The main factors contributing to the AV rear-end scenario were location outside the intersection in the intersection-related area, traffic signal control, autonomous engaged mode, mixed-use or public land, and weekdays, while those for lane change scenarios were on-street parking and the time of 8:00 a.m. Important causes of rear-end crashes attributable to the AV were inadequate stop and deceleration decisions by the AV's automated driving system (ADS) and insufficient collision avoidance decisions in lane change crashes. Identification of the pre-crash characteristics and contributing factors provide new insight into AV crash causation and can be used in the determination of the AV's operational design domain and the development and optimization of the AV's ADS at intersections. These findings can also play a role in guiding traffic safety agencies to discover AV hotspots and propose AV management regulations.

Nintedanib inhibits normal human vitreous-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells.

PURPOSE: In this study, we aim to investigate the potential of nintedanib as a therapeutic approach to proliferative vitreoretinopathy (PVR), which is the leading cause of failure in retinal detachment repair. PVR is characterized by the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and understanding the effects of nintedanib on EMT in the normal human vitreous (HV)-induced RPE cells is crucial. METHODS: Our research focuses on assessing the impact of nintedanib on HV-induced EMT in human retinal pigment epithelial (ARPE-19) cells in vitro. We employed various techniques, including quantitative real-time PCR (qPCR), western blot analysis, and immunofluorescence staining, to evaluate the mRNA and protein expression of EMT biomarkers in HV-induced ARPE-19 cells. Additionally, we measured the proliferation of RPE cells using cell counting, CCK-8, and Ki-67 assays. Migration was assessed through wound healing and transwell migration assays, while contraction was determined using a collagen gel contraction assay. Morphological changes were examined using phase-contrast microscopy. RESULTS: Our results demonstrate that nintedanib selectively attenuates the upregulation of mesenchymal markers in HV-induced ARPE-19 cells, at both the mRNA and protein levels. Furthermore, nintedanib effectively suppresses the HV-induced proliferation, migration, and contraction of ARPE-19 cells, while maintaining the cells' basal activity. These findings strongly suggest that nintedanib exhibits protective effects against EMT in ARPE-19 cells and could be a promising therapeutic option for PVR. CONCLUSIONS: By elucidating the anti-EMT effects of nintedanib in HV-induced RPE cells, our study highlights the potential of this oral triple tyrosine kinase inhibitor in the treatment of PVR. These findings contribute to the growing body of research aimed at developing novel strategies to prevent and manage PVR, ultimately improving the success rates of retinal detachment repair.

Evaluation of Microplastics and Microcystin-LR Effect for Asian Clams (Corbicula fluminea) by a Metabolomics Approach.

Microplastics (MP) and microcystins (MCs) are two co-occurring pollutants in freshwater ecosystems that pose significant risks to aquatic organisms and human health. This study investigates the interactions between MP and MCs and their effects on the metabolic responses of freshwater aquaculture. Asian clams have been used as an indicator of microplastic pollution in freshwater ecosystems. The present study investigates metabolic responses of Asian clams during microplastic and microcystin-LR stress to identify health impacts and elucidate mechanistic effects of external stressors on Asian clams. A liquid chromatography/mass spectrometry (LC-MS)-based metabolomics approach was used to identify metabolic perturbations and histological section technique was used to assess changes of tissues from different Asian clam treatment groups. The results showed significantly pathological changes in the gills and hepatopancreas in experimental clam compared to control (healthy) clam. Metabolomics revealed alterations of many metabolites in the hepatopancreas of six Asian clam comparison groups, reflecting perturbations in several molecular pathways, including energy metabolism, amino acid metabolism, protein degradation/tissue damage, and oxidative stress. Overall, this study emphasizes the importance of understanding the interactions between MP and MCs and the need for proactive measures to safeguard freshwater ecosystems and human health.

Resolution enhancement of tongue tactile image based on deconvolution neural network.

To reproduce the tactile perception of multiple contacts on the human tongue surface, it is necessary to use a pressure measurement device with high spatial resolution. However, reducing the size of the array sensing unit and optimizing the lead arrangement still pose challenges. This article describes a deconvolution neural network (DNN) for improving the resolution of tongue surface tactile imaging, which alleviates this tradeoff between tactile sensing performance and hardware simplicity. The model can work without high-resolution tactile imaging data of tongue surface: First, in the compression test using artificial tongues, the tactile image matrix (7 × 7) with low resolution can be acquired by sensor array with a sparse electrode arrangement. Then, through finite element analysis modeling, combined with the distribution rule of additional stress on the two-dimensional plane, the pressure data around the existing detection points are calculated, further expanding the tactile image matrix data amount. Finally, the DNN, based on its efficient nonlinear reconstruction attributes, uses the low-resolution and high-resolution tactile imaging matrix generated by compression test and finite element simulation, respectively, to train, and outputs high-resolution tactile imaging information (13 × 13) closer to the tactile perception of the tongue surface. The results show that the overall accuracy of the tactile image matrix calculated by this model is above 88%. Then, we deduced the spatial difference graph of the resilience index of the three kinds of ham sausages through the high-resolution tactile imaging matrix.

Nintedanib prevents TGF-ß2-induced epithelial-mesenchymal transition in retinal pigment epithelial cells.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key fibrosis pathogenesis in proliferative vitreoretinopathy (PVR). However, few medicines can prevent proliferative membranes and cell proliferation in the clinic. Nintedanib, a tyrosine kinase inhibitor, has been shown to prevent fibrosis and be anti-inflammatory in multiple organ fibrosis. In our study, 0.1, 1, 10 µM nintedanib was added to 20 ng/mL transforming growth factor beta 2 (TGF-ß2)-induced EMT in ARPE-19 cells. Western blot and immunofluorescence assay showed that 1 µM nintedanib suppressed TGF-ß2-induced E-cadherin expression decreased and Fibronectin, N-cadherin, Vimentin, and α-SMA expression increased. Quantitative real-time PCR results showed that 1 µM nintedanib decreased TGF-ß2-induced increase in SNAI1, Vimentin, and Fibronectin expression and increased TGF-ß2-induced decrease in E-cadherin expression. In addition, the CCK-8 assay, wound healing assay, and collagen gel contraction assay also showed that 1 µM nintedanib ameliorated TGF-ß2-induced cell proliferation, migration, and contraction, respectively. These results suggested that nintedanib inhibits TGF-ß2-induced EMT in ARPE-19 cells, which may be a potential pharmacological treatment for PVR.

Acid sphingomyelinase promotes diabetic cardiomyopathy via NADPH oxidase 4 mediated apoptosis.

BACKGROUND: Increased acid sphingomyelinase (ASMase) activity is associated with insulin resistance and cardiac dysfunction. However, the effects of ASMase on diabetic cardiomyopathy (DCM) and the molecular mechanism(s) underlying remain to be elucidated. We here investigated whether ASMase caused DCM through NADPH oxidase 4-mediated apoptosis. METHODS AND RESULTS: We used pharmacological and genetic approaches coupled with study of murine and cell line samples to reveal the mechanisms initiated by ASMase in diabetic hearts. The protein expression and activity of ASMase were upregulated, meanwhile ceramide accumulation was increased in the myocardium of HFD mice. Inhibition of ASMase with imipramine (20 mg Kg-1 d-1) or siRNA reduced cardiomyocyte apoptosis, fibrosis, and mitigated cardiac hypertrophy and cardiac dysfunction in HFD mice. The similar effects were observed in cardiomyocytes treated with high glucose (HG, 30 mmol L-1) + palmitic acid (PA, 100 µmol L-1) or C16 ceramide (CER, 20 µmol L-1). Interestingly, the cardioprotective effect of ASMase inhibition was not accompanied by reduced ceramide accumulation, indicating a ceramide-independent manner. The mechanism may involve activated NADPH oxidase 4 (NOX4), increased ROS generation and triggered apoptosis. Suppression of NOX4 with apocynin prevented HG + PA and CER incubation induced Nppb and Myh7 pro-hypertrophic gene expression, ROS production and apoptosis in H9c2 cells. Furthermore, cardiomyocyte-specific ASMase knockout (ASMaseMyh6KO) restored HFD-induced cardiac dysfunction, remodeling, and apoptosis, whereas NOX4 protein expression was downregulated. CONCLUSIONS: These results demonstrated that HFD-mediated activation of cardiomyocyte ASMase could increase NOX4 expression, which may stimulate oxidative stress, apoptosis, and then cause metabolic cardiomyopathy.

Portable Multi-Channel Electrochemical Device with Good Interaction and Wireless Connection for On-Site Testing.

It is very important to rapidly test the key indicators of water in the field to fully evaluate the quality of the regional water environment. However, a high-resolution measuring device that can generate small currents for low-concentration analytes in water samples is often bulky, complex to operate, and difficult for data sharing. This work introduces a portable multi-channel electrochemical device with a small volume, good interaction, and data-sharing capabilities called PMCED. The PMCED provides an easy-to-operate graphical interactive interface to conveniently set the parameters for cyclic voltammetry or a differential pulse method performed by the four electrode channels. At the same time, the device, with a current sensitivity of 100 nA V-1, was applied to the detection of water samples with high background current and achieved a high-resolution measurement at low current levels. The PMCED uses the Narrow Band Internet of Things (NB-IoT) to meet the needs for uploading data to the cloud in remote areas. The electrochemical signal preprocessing and chemometrics models run in the cloud, and the final results are visualized on a web page, providing a remote access channel for on-site testing results.

In situ quantitative assessment of food oral processing parameters: A review of feasible techniques and devices.

Oral processing is a combination of various actions, the detailed description of which has always been the subject of relevant research. By means of imaging technology and sensory evaluation, more knowledge of oral processing have been accumulated. Presently, the advances in sensory technology have added quantitative parameters to the qualitative description of oral processing, which also enriched the specifics of each action. Previous studies have shown that oral processing includes lip closure, dental occlusion, masticatory muscles activity, tongue movement, and swallowing, whose processing contains rich information such as the movement of organ and the intensity of organ contacts. "Quantification" was taken in this review as the basic feature of in situ detection information, the relevant parameters and feasible methods for the quantitative description of each activity was recorded in detail. In addition, basic problems and feasible optimization schemes of the existing in situ detection device are also proposed in the hope of promoting the development of in situ detection device thus providing available information for the description of oral processing.

Effect of miRNA-200b on the proliferation of liver cancer cells via targeting SMYD2/p53 signaling pathway. / MiR-200b通过靶向调控SMYD2/p53信号通路抑制肝癌细胞增殖（英文）.

OBJECTIVES: Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism. METHODS: Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Secondly, we evaluated the interaction between miR-200b and SMYD2 using dual-luciferase reporter assay. Thirdly, we elucidated the effect of miR-200b on SMYD2 and its downstream targets p53/CyclinE1. Finally, we silenced SMYD2 in hepatocellular carcinoma cell lines to investigate its effect on tumor proliferation and cell cycle progression, and further confirmed the correlation among SMYD2 and p53/CyclinE1. RESULTS: Compared with the matched adjacent non-tumor liver tissues, miR-200b was obviously decreased, and SMYD2 was significantly increased in hepatocellular carcinoma (both P<0.05). Spearman's rank correlation revealed that miR-200b expression was negatively correlated with SMYD2 (P<0.01). Computer algorithm and dual-luciferase reporter assay revealed that miR-200b directly targeted and suppressed SMYD2 in HEK 293T cells. The down-regulated miR-200b expression promoted hepatoma cell proliferation (P<0.05) and increased SMYD2 expression(P<0.01), while the up-regulated expression of miR-200b had an opposite effect. The knockdown of SMYD2 suppressed the proliferation of MHCC-97L cells (P<0.01), down-regulated CyclinE1, and up-regulated p53 expression (both P<0.05). CONCLUSIONS: MiR-200b is involved in hepatocellular carcinoma progression via targeting SMYD2 and regulating SMYD2/p53/CyclinE1 signaling pathway and may be used as a potential target for hepatocellular carcinoma treatment.

Analysis of clinical characteristics of mesalazine-induced cardiotoxicity.

Background: Mesalazine is the first-line inflammatory bowel disease (IBD) treatment. However, it can cause fatal cardiotoxicity. We aimed to analyze the clinical characteristics of mesalazine-induced cardiotoxicity and provide evidence for clinical diagnosis, treatment, and prevention. Methods: We collected Chinese and English literature on mesalazine-induced cardiotoxicity from 1970 to 2021 for retrospective analysis. Results: A total of 52 patients (40 males and 12 females) were included, with a median age of 24.5 years (range 9-62) and a median onset time of 14 days (range 2-2880). Cardiotoxicity manifested as myocarditis, pericarditis, and cardiac pericarditis. The main clinical manifestations are chest pain (82.7%), fever (46.2%), and respiratory symptoms such as dyspnea and cough (40.4%). The levels of troponin T, creatine kinase, C-reactive protein, leukocyte count, erythrocyte sedimentation rate, and other biochemical markers were significantly increased. Cardiac imaging often suggests myocardial infarction, pericardial effusion, myocardial necrosis, and other symptoms of cardiac injury. It is essential to discontinue mesalamine immediately in patients with cardiotoxicity. Although corticosteroids are a standard treatment option, the benefits remain to be determined. Re-challenge of mesalamine should be carefully considered as cardiotoxic symptoms may reoccur. Conclusion: Mesalazine may cause cardiotoxicity in patients with inflammatory bowel disease, which should be comprehensively diagnosed based on clinical manifestations, biochemical indicators, and cardiac function imaging examinations. Mesalazine should be immediately discontinued, and corticosteroids may be an effective treatment for cardiotoxicity.

Application and Progress of Chemometrics in Voltammetric Biosensing.

The voltammetric electrochemical sensing method combined with biosensors and multi-sensor systems can quickly, accurately, and reliably analyze the concentration of the main analyte and the overall characteristics of complex samples. Simultaneously, the high-dimensional voltammogram contains the rich electrochemical features of the detected substances. Chemometric methods are important tools for mining valuable information from voltammetric data. Chemometrics can aid voltammetric biosensor calibration and multi-element detection in complex matrix conditions. This review introduces the voltammetric analysis techniques commonly used in the research of voltammetric biosensor and electronic tongues. Then, the research on optimizing voltammetric biosensor results using classical chemometrics is summarized. At the same time, the incorporation of machine learning and deep learning has brought new opportunities to further improve the detection performance of biosensors in complex samples. Finally, smartphones connected with miniaturized voltammetric biosensors and chemometric methods provide a high-quality portable analysis platform that shows great potential in point-of-care testing.

Long non-coding RNA DDX11-AS1 promotes the proliferation and migration of glioma cells by combining with HNRNPC.

Glioma is a malignant tumor of the central nervous system with complex pathogenesis, difficult operation, and a high postoperative recurrence rate. At present, there is still a lack of effective treatment. Long non-coding RNA DDX11 antisense RNA 1 (DDX11-AS1) has been shown to promote tumor development, such as hepatocellular carcinoma, esophageal cancer, etc. However, its molecular mechanism in glioma is poorly understood. In this study, we found that the expression of DDX11-AS1 was elevated in glioma tissues, and patients with high expression of DDX11-AS1 had poor prognosis. DDX11-AS1 was a potential prognostic marker. Functionally, DDX11-AS1 promoted glioma cell proliferation and migration. Mechanistically, DDX11-AS1 interacted with RNA-binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) to promote Wnt/ß-catenin and AKT pathways and the epithelial-mesenchymal transition process. In summary, our study manifests that the DDX11-AS1/HNRNPC axis may play a vital part in the occurrence and development of glioma, which provides new ideas and therapeutic targets for the diagnosis, treatment, and prognosis of glioma.

Hierarchical Encoder-Decoder With Soft Label-Decomposition for Mitochondria Segmentation in EM Images.

Semantic segmentation of mitochondria from electron microscopy (EM) images is an essential step to obtain reliable morphological statistics about mitochondria. However, automatically delineating plenty of mitochondria of varied shapes from complex backgrounds with sufficient accuracy is challenging. To address these challenges, we develop a hierarchical encoder-decoder network (HED-Net), which has a three-level nested U-shape architecture to capture rich contextual information. Given the irregular shape of mitochondria, we introduce a novel soft label-decomposition strategy to exploit shape knowledge in manual labels. Rather than simply using the ground truth label maps as the unique supervision in the model training, we introduce additional subcategory-aware supervision by softly decomposing each manual label map into two complementary label maps according to mitochondria's ovality. The three label maps are integrated with our HED-Net to supervise the model training. While the original label map guides the network to segment all the mitochondria of varied shapes, the auxiliary label maps guide the network to segment subcategories of mitochondria of circular shape and elliptic shape, respectively, which are much more manageable tasks. Extensive experiments on two public benchmarks show that our HED-Net performs favorably against state-of-the-art methods.

Histidine kinase NME1 and NME2 are involved in TGF-ß1-induced HSC activation and CCl4-induced liver fibrosis.

Histidine phosphorylation (pHis) was first reported in 1962. There are few studies on pHis because of the thermal and acidic instability of pHis and the lack of specific methods to detect it. pHis has two isomers of 1-phosphate histidine (1-pHis) and 3-phosphate histidine (3-pHis). pHis antibodies have been developed recently and have promoted research in this field. In this study, we established a CCl4-induced liver fibrosis model in C57 mice and a TGF-ß1-induced HSC activation model in LX-2 cells, to study the role of histidine phosphorylation. The expression of histidine kinases NME1 and NME2 was increased, histidine phosphatase PGAM5 and PHPT1 was unchanged, and 1-pHis and 3-pHis were increased in the in vivo and in vitro models. The expression of LHPP was decreased in the in vivo model but not in the in vitro model. To further study the role of NME1, NME2, and histidine phosphorylation in HSC activation, we silenced NME1 or NME2 and administered TGF-ß1 in LX-2 cells. The results showed silencing NME1 or NME2 decreased TGF-ß1-induced pHis levels and the expression of α-SMA and COL1A1, indicating the activation of HSC was suppressed. Then, we found the inhibitory effect on HSC activation is due to reduced phosphorylation of Smad2 and Smad3. In summary, our studies indicate that NME1 and NME2 are involved in TGF-ß1-induced HSC activation and CCl4-induced liver fibrosis, which may be mediated by histidine phosphorylation.

Lnc GNG12-AS1 knockdown suppresses glioma progression through the AKT/GSK-3ß/ß-catenin pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly being regarded as regulators of glioma development. Notably, some studies report that GNG12-AS1 plays important functions and molecular mechanism in breast cancer, but there are no existing studies in glioma. OBJECTIVE: To analyze the biological functions and potential mechanisms of GNG12-AS1 in glioma. METHODS: We detected the expression of GNG12-AS1 in glioma tissues through analyzing TCGA data as well as our clinical samples. We then evaluated cell proliferation through MTT assay and colony formation and cell migration by transwell assay, wound healing assay and single cell tracking assay. After, we analyzed the effects of the AKT/GSK-3ß/ß-catenin through Western blotting and utilized the ß-catenin agonist SKL2001 for the rescue experiment. RESULTS: GNG12-AS1 was highly expressed in glioma tissues. The silence of GNG12-AS1 inhibited the proliferation, migration and epithelial-mesenchymal transition of glioma cells, and reduced the activity of the AKT/GSK-3ß/ß-catenin pathway. Notably, SKL2001 could reverse cell migration as well as ß-catenin expression in glioma cells with lower GNG12-AS1 expression. CONCLUSIONS: GNG12-AS1 regulates proliferation and migration of glioma cells through the AKT/GSK-3ß/ß-catenin signaling and can perhaps be a new target for the treatment of glioma.

Correction to: Transcranial Magneto-Acoustic Stimulation Improves Neuroplasticity in Hippocampus of Parkinson's Disease Model Mice.

The authors would like to correct X. Zhou's grant number from the National Natural Science Foundation of China to 81601633.

Effects of UGT1A1 Polymorphism, Gender and Triglyceride on the Pharmacokinetics of Telmisartan in Chinese Patients with Hypertension: A Population Pharmacokinetic Analysis.

BACKGROUND AND OBJECTIVE: Telmisartan is an angiotensin receptor blocker used for the treatment of hypertension. The effects of gender and uridine diphosphate-glycosytransferase 1A1 (UGT1A1) genetic polymorphisms (rs4124874, rs4148323, and rs6742078) on telmisartan plasma concentration and blood pressure in Chinese patients with hypertension have been reported previously. In this study, we aimed to develop a population pharmacokinetic (PopPK) model to quantify the effects of gender and UGT1A1 polymorphisms on the pharmacokinetics of telmisartan. METHODS: Population pharmacokinetic analyses were performed using data collected prospectively from 58 Chinese patients with mild to moderate essential hypertension (aged 45-72 years; 36 men, 22 women) receiving 80 mg/day telmisartan orally for 4 weeks. Blood samples were collected in heparinized tubes at 0, 0.5, 1, and 6 h on day 28 after telmisartan administration. The plasma concentrations and UGT1A1 genetic variants were determined by high-performance liquid chromatography-mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, respectively. RESULTS: A two-compartment pharmacokinetic structural model with first-order elimination and absorption best described the pharmacokinetic characteristics of telmisartan. Gender and triglyceride influenced the apparent oral clearance (CL) of telmisartan. UGT1A1 (rs4124874) affected the bioavailability (F1) of telmisartan. Lower CL and bioavailability resulted in higher plasma concentrations being observed in female subjects with UGT1A1 CC or CA genotype and high triglyceride. CONCLUSION: A PopPK model of telmisartan was established to confirm that UGT1A1 genotype, gender and triglyceride can affect the pharmacokinetics of telmisartan in Chinese patients with hypertension. Our findings can provide relevant pharmacokinetic parameters for further study of telmisartan.