Pericytes Regulate Cerebral Perfusion through VEGFR1 in Ischemic Stroke.

Neurons in the penumbra (the area surrounding ischemic tissue that consists of still viable tissue but with reduced blood flow and oxygen transport) may be rescued following stroke if adequate perfusion is restored in time. It has been speculated that post-stroke angiogenesis in the penumbra can reduce damage caused by ischemia. However, the mechanism for neovasculature formation in the brain remains unclear and vascular-targeted therapies for brain ischemia remain suboptimal. Here, we show that VEGFR1 was highly upregulated in pericytes after stroke. Knockdown of VEGFR1 in pericytes led to increased infarct area and compromised post-ischemia vessel formation. Furthermore, in vitro studies confirmed a critical role for pericyte-derived VEGFR1 in both endothelial tube formation and pericyte migration. Interestingly, our results show that pericyte-derived VEGFR1 has opposite effects on Akt activity in endothelial cells and pericytes. Collectively, these results indicate that pericyte-specific expression of VEGFR1 modulates ischemia-induced vessel formation and vascular integrity in the brain.

A radiomics nomogram may improve the prediction of IDH genotype for astrocytoma before surgery.

OBJECTIVES: To develop and validate a radiomics nomogram to preoperative prediction of isocitrate dehydrogenase (IDH) genotype for astrocytomas, which might contribute to the pretreatment decision-making and prognosis evaluating. METHODS: One hundred five astrocytomas (Grades II-IV) with contrast-enhanced T1-weighted imaging (CE-T1WI), T2 fluid-attenuated inversion recovery (T2FLAIR), and apparent diffusion coefficient (ADC) map were enrolled in this study (training cohort: n = 74; validation cohort: n = 31). IDH1/2 genotypes were determined using Sanger sequencing. A total of 3882 radiomics features were extracted. Support vector machine algorithm was used to build the radiomics signature on the training cohort. Incorporating radiomics signature and clinico-radiological risk factors, the radiomics nomogram was developed. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess these models. Kaplan-Meier survival analysis and log rank test were performed to assess the prognostic value of the radiomics nomogram. RESULTS: The radiomics signature was built by six selected radiomics features and yielded AUC values of 0.901 and 0.888 in the training and validation cohorts. The radiomics nomogram based on the radiomics signature and age performed better than the clinico-radiological model (training cohort, AUC = 0.913 and 0.817; validation cohort, AUC = 0.900 and 0.804). Additionally, the survival analysis showed that prognostic values of the radiomics nomogram and IDH genotype were similar (log rank test, p < 0.001; C-index = 0.762 and 0.687; z-score test, p = 0.062). CONCLUSIONS: The radiomics nomogram might be a useful supporting tool for the preoperative prediction of IDH genotype for astrocytoma, which could aid pretreatment decision-making. KEY POINTS: • The radiomics signature based on multiparametric and multiregional MRI images could predict IDH genotype of Grades II-IV astrocytomas. • The radiomics nomogram performed better than the clinico-radiological model, and it might be an easy-to-use supporting tool for IDH genotype prediction. • The prognostic value of the radiomics nomogram was similar with that of the IDH genotype, which might contribute to prognosis evaluating.

MRI radiomics for predicting poor disease-free survival in muscle invasive bladder cancer: the results of the retrospective cohort study.

OBJECTIVES: To develop an MRI radiomic nomogram capable of identifying muscle invasive bladder cancer (MIBC) patients with high-risk molecular characteristics related to poor 2-year disease-free survival (DFS). METHODS: We performed a retrospective analysis of DNA sequencing data, prognostic information, and radiomics features from 91 MIBC patients at stages T2-T4aN0M0 without history of immunotherapy. To identify risk stratification, we employed Cox regression based on TP53 mutation status and tumor mutational burden (TMB) level. Radiomics signatures were selected using the least absolute shrinkage and selection operator (LASSO) to construct a nomogram based on logistic regression for predicting the stratification in the training cohort. The predictive performance of the nomogram was assessed in the testing cohort using receiver operator curve (ROC), Hosmer-Lemeshow (HL) test, clinical impact curve (CIC), and decision curve analysis (DCA). RESULTS: Among 91 participants, the mean TMB value was 3.3 mut/Mb, with 60 participants having TP53 mutations. Patients with TP53 mutations and a below-average TMB value were identified as high risk and had a significantly poor 2-year DFS (hazard ratio = 4.36, 95% CI 1.82-10.44, P < 0.001). LASSO identified five radiomics signatures that correlated with the risk stratification. In the testing cohort, the nomogram achieved an area under the ROC curve of 0.909 (95% CI 0.789-0.991) and an accuracy of 0.889 (95% CI 0.708-0.977). CONCLUSION: The molecular risk stratification based on TP53 mutation status combined with TMB level is strongly associated with DFS in MIBC. Radiomics signatures can effectively predict this stratification and provide valuable information to clinical decision-making.

Evaluation of Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis in Southwest China.

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB).

Redistribution of Histone Marks on Inflammatory Genes Associated With Intracerebral Hemorrhage-Induced Acute Brain Injury in Aging Rats.

The contribution of histone mark redistribution to the age-induced decline of endogenous neuroprotection remains unclear. In this study, we used an intracerebral hemorrhage (ICH)-induced acute brain injury rat model to study the transcriptional and chromatin responses in 13- and 22-month-old rats. Transcriptome analysis (RNA-seq) revealed that the expression of neuroinflammation-associated genes was systematically upregulated in ICH rat brains, irrespective of age. Further, we found that interferon-γ (IFN-γ) response genes were activated in both 13- and 22-month-old rats. Anti-IFN-γ treatment markedly reduced ICH-induced acute brain injury in 22-month-old rats. At the chromatin level, ICH induced the redistribution of histone modifications in the promoter regions, especially H3K4me3 and H3K27me3, in neuroinflammation-associated genes in 13- and 22-month-old rats, respectively. Moreover, ICH-induced histone mark redistribution and gene expression were found to be correlated. Collectively, these findings demonstrate that histone modifications related to gene expression are extensively regulated in 13- and 22-month-old rats and that anti-IFN-γ is effective for ICH treatment, highlighting the potential of developing therapies targeting histone modifications to cure age-related diseases, including brain injury and neuroinflammation.

Restriction of photoinduced twisted intramolecular charge transfer.

An intensive investigation of structure-property relationships in the aggregation-induced enhanced emission (AIEE) of luminescent compounds is essential for the rational design of highly emissive solid-state materials. In the AIEE-active compounds N,N'-bis[3-hydroxy-4-(2'-benzothiazolyl)phenyl]isophthalamide and N,N'-bis[3-hydroxy-4-(2'-benzothiazolyl)phenyl]-5-tert-butylisophthalamide, fast photoinduced twisted intramolecular charge transfer (TICT) of the enol excited state is found to be mainly responsible for the weak emission of their dilute solutions. The photoinduced TICT enol excited state is formed with a greatly distorted configuration, due to the large rotation about the C-N single bond. This facilitates nonradiative TICT decay from the normal enol excited state to the highly twisted enol excited state, rather than proton-transfer decay to the keto excited state. In aggregates, photoinduced nonradiative deactivation of TICT is strongly prohibited, so that excited-state intramolecular proton transfer (ESIPT) becomes the dominant decay, and hence contributes greatly to the subsequent emission enhancement of the keto form. Molecular design and investigation of analogous single-armed compounds further verifies this kind of AIEE mechanism.

Whole-tumor radiomics analysis of DKI and DTI may improve the prediction of genotypes for astrocytomas: A preliminary study.

PURPOSE: To test whether the whole-tumor radiomics analysis of DKI and DTI images could predict IDH and MGMTmet genotypes of astrocytomas. METHOD: Sixty-two astrocytomas were enrolled. 364 radiomics features of whole tumor were extracted from mean-kurtosis (MK), and mean-diffusivity (MD) images, respectively. The multivariable logistic regression was used to select the most meaningful radiomics features for predicting IDH and MGMTmet genotypes. A radiomics model was built by logistic linear regression. A combined model was established based on selected radiomic, radiological and clinical features. To assess the difference between the models, the Z-test was performed. RESULTS: The radiomics model built using the three most informative radiomics features for each genotype yielded an AUC of 0.831 ((95 % confidence interval [CI]: 0.721-0.918) for predicting IDH genotype, and 0.835 (95 %CI: 0.686-0.951) for MGMTmet genotype. A combined model for predicting IDH based on the radiomics score, age, and degree of edema reached an AUC of 0.885 (95 %CI: 0.802-0.955) and a combined model for predicting MGMTmet based on radiomics score and edema degree reached an AUC of 0.859 (95 %CI: 0.751-0.945) which was not significantly higher than the radiomics only model (P =  0.081). CONCLUSIONS: The radiomics models via an objective whole-tumor analysis of MK and MD maps were independent imaging biomarkers for predicting IDH and MGMTmet genotypes, and the combined model further improved the performance for IDH, but not for MGMTmet.

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage.

Oxylipins are a series of bioactive lipid metabolites derived from polyunsaturated fatty acids that are involved in cerebral homeostasis and the development of intracerebral hemorrhage (ICH). However, comprehensive quantification of the oxylipin profile in ICH remains unknown. Therefore, an ICH mouse model was constructed and liquid chromatography tandem mass spectrometry was then performed to quantify the change in oxylipins in ICH. The expression of the oxylipin relative enzymes was also reanalyzed based on RNA-seq data from our constructed ICH dataset. A total of 58 oxylipins were quantifiable and the levels of 17 oxylipins increased while none decreased significantly in the first 3 days following ICH. The most commonly increased oxylipins in ICH were derived from AA (10/17) and EPA (4/17) followed by LA (2/17) and DHA (1/17). 18-HEPE from EPA was the only oxylipin that remained significantly increased from 0.5 to 3 days following ICH. Furthermore, 14 of the increased oxylipins reached a peak level on the first day of ICH, and soon decreased while five oxylipins (PGJ2, 15-oxo-ETE, 12-HEPE, 18-HEPE, and 5-oxo-ETE) had increased 3 days after ICH suggesting that the profile shifted with the progression of ICH. In our constructed RNA-seq dataset based on ICH rats, 90 oxylipin relative molecules were detected except for COX. Among these, Cyp4f18, Cyp1b1, Cyp2d3, Cyp2e1, Cyp1a1, ALOX5AP, and PLA2g4a were found up-regulated and Cyp26b1 was found to decrease in ICH. In addition, there was no significant change in sEH in ICH. This study provides fundamental data on the profile of oxylipins and their enzymes in ICH. We found that the profile shifted as the progression of ICH and the metabolism of arachidonic acid and eicosapentaenoic acid was highly affected in ICH, which will help further studies explore the functions of oxylipins in ICH.

Prdx1 Reduces Intracerebral Hemorrhage-Induced Brain Injury via Targeting Inflammation- and Apoptosis-Related mRNA Stability.

RNA-binding proteins (RBPs) have been shown to be involved in posttranscriptional regulation, which plays an important role in the pathophysiology of intracerebral hemorrhage (ICH). Peroxiredoxin 1 (Prdx1), an RBP, plays an important role in regulating inflammation and apoptosis. On the basis that inflammation and apoptosis may contribute to ICH-induced brain injury, in this study, we used ICH models coupled with in vitro experiments, to investigate the role and mechanism of Prdx1 in regulating inflammation and apoptosis by acting as an RBP after ICH. We first found that Prdx1 was significantly up-regulated in response to ICH-induced brain injury and was mainly expressed in astrocytes and microglia in ICH rat brains. After overexpressing Prdx1 by injecting adeno-associated virus (AAV) into the striatum of rats at 3 weeks, we constructed ICH models and found that Prdx1 overexpression markedly reduced inflammation and apoptosis after ICH. Furthermore, RNA immunoprecipitation combined with high-throughput sequencing (RIP-seq) in vitro revealed that Prdx1 affects the stability of inflammation- and apoptosis-related mRNA, resulting in the inhibition of inflammation and apoptosis. Finally, overexpression of Prdx1 significantly alleviated the symptoms and mortality of rats subjected to ICH. Our results show that Prdx1 reduces ICH-induced brain injury by targeting inflammation- and apoptosis-related mRNA stability. Prdx1 may be an improved therapeutic target for alleviating the brain injury caused by ICH.

Improving survival prediction of high-grade glioma via machine learning techniques based on MRI radiomic, genetic and clinical risk factors.

OBJECTIVES: To develop a radiomic signature to predict overall survival (OS) for high-grade glioma (HGG), and construct a nomogram by combining selected radiomic, genetic and clinical risk factors to further improve the performance of the risk model. MATERIALS AND METHODS: 147 cases of HGG with MRI images, genetic data, clinical data were studied, wherein 112 patients were used as training cohort, and 35 patients were as independent test cohort. Radiomics features were extracted from tumor area and peritumoral edema area on CE-T1WI and T2FLAIR images. Association between radiomics signature, genetic, clinical risk factors and OS was explored by Kaplan-Meier survival analysis and log rank test. The multivariate Cox regression analysis was trained with radiomic features along with selected genetic and clinical risk factors, which was presented as a nomogram. RESULTS: The radiomic signature constructed by 11 radiomics features stratified patients into low- and high-risk groups, and the C-Index for OS prediction was 0.707 and 0.711 in training and test cohorts, respectively. The multivariable Cox regression analysis identified radiomics signature (hazard ratio (HR): 2.18, P = 0.005), IDH (HR: 0.490, P = 0.007) and age (HR: 1.039, P = 0.005) as independent risk factors. A nomogram combining these independent risk factors further improved the performance for OS estimation (C-index = 0.764 and 0.758 in training and test cohorts, respectively). CONCLUSION: The radiomics signature is a new prognostic biomarker for HGG. A nomogram incorporating radiomics signature, IDH and age improved the performance of OS estimation, which might be a new complement to the treatment guidelines of glioma.

Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage.

Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.

Mechanism of aqueous ultrasonic reaction: controlled synthesis, luminescence properties of amorphous cluster and nanocrystalline CdSe.

A novel sonochemical method was found to prepare amorphous CdSe cluster and hexagonal nanocrystalline CdSe in aqueous solution. An interfacial mechanism for the sonochemical formation of CdSe nanoparticles was confirmed. The exploration for luminescence properties of the as-prepared CdSe nanoparticles revealed its wide application in many fields.

Drosophila morphogenesis: tissue force laws and the modeling of dorsal closure.

Dorsal closure, a stage of Drosophila development, is a model system for cell sheet morphogenesis and wound healing. During closure, two flanks of epidermal tissue progressively advance to reduce the area of the eye-shaped opening in the dorsal surface, which contains amnioserosa tissue. To simulate the time evolution of the overall shape of the dorsal opening, we developed a mathematical model, in which contractility and elasticity are manifest in model force-producing elements that satisfy force-velocity relationships similar to muscle. The action of the elements is consistent with the force-producing behavior of actin and myosin in cells. The parameters that characterize the simulated embryos were optimized by reference to experimental observations on wild-type embryos and, to a lesser extent, on embryos whose amnioserosa was removed by laser surgery and on myospheroid mutant embryos. Simulations failed to reproduce the amnioserosa-removal protocol in either the elastic or the contractile limit, indicating that both elastic and contractile dynamics are essential components of the biological force-producing elements. We found it was necessary to actively upregulate forces to recapitulate both the double and single-canthus nick protocols, which did not participate in the optimization of parameters, suggesting the existence of additional key feedback mechanisms.