A field trial for remediation of multi-metal contaminated soils using the combination of fly ash stabilization and Zanthoxylumbungeanum- Lolium perenne intercropping system.

Insitu stabilization and phytoextraction are considered as two convenient and effective technologies for the remediation of toxic elements (TEs) in soils. However, the effectiveness of these two remediation technologies together on the bioavailability and phytoextraction of TEs in field trials has not been explored yet. Specifically, the remediation potential of fly ash (FA; as stabilizing agent) and ryegrass (as a TE accumulator) intercropped with a target crop for soil polluted with multiple TEs has not been investigated yet, particularly in long-term field trials. Therefore, in this study, a six-month combined remediation field experiment of FA stabilization and/or ryegrass intercropping (IR) was carried out on the farmland soils contaminated with As, Cd, Cr, Cu, Hg, Ni, Pb and Zn where Zanthoxylumbungeanum (ZB) trees as native crops were grown for years. The treatments include soil cultivated alone with ZB untreated- (control) and treated-with FA (FA), produced by burning lignite in Shaanxi Datong power plant, China, soil cultivated with ZB and ryegrass untreated- (IR) and treated-with FA (FA + IR). This was underpinned by a large-scale survey in Daiziying (China), which showed that the topsoils were polluted by Cd, Cu, Hg and Pb, and that Hg and Pb contents in the Zanthoxylumbungeanum fruits exceeded their allowable limits. The TEs contents in the studied FA were lower than their total element contents in the soil. The DTPA-extractable TEs contents of the remediation modes were as follows: FA < FA + IR < IR < control. Notably, TEs contents in the ZB fruits were lowest under the FA + IR treatment, which were decreased by 27.6% for As, 42.3% for Cd, 16.7% for Cr, 30.5% for Cu, 23.1% for Hg, 15.5% for Ni, 33.2% for Pb and 38.1% for Zn compared with the control treatment. Whereas the FA + IR treatment enhanced TEs contents in ryegrass shoots and roots, and the TEs contents in ryegrass shoots were below their regulatory limits for fodder crops. The findings confirmed that the combined remediation strategy, i.e., FA (with low content of TEs) stabilization effect and intercropping of ZB (target crop) and ryegrass (accumulating plant) could provide a prospective approach to produce target plants within safe TEs thresholds with greater economic benefits, while remediating soils polluted with multiple TEs and mitigating the potential ecological and human health risk. Those results are of great applicable concern.

Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

Truncated Dyrk1A aggravates neuronal apoptosis by inhibiting ASF-mediated Bcl-x exon 2b inclusion.

AIM: Aggravated neuronal loss, caused mainly by neuronal apoptosis, is observed in the brain of patients with Alzheimer's disease (AD) and animal models of AD. A truncated form of Dual-specific and tyrosine phosphorylation-regulated protein kinase 1A (Dyrk1A) plays a vital role in AD pathogenesis. Downregulation of anti-apoptotic Bcl-xL is tightly correlated with neuronal loss in AD. However, the molecular regulation of neuronal apoptosis and Bcl-x expression by Dyrk1A in AD remains largely elusive. Here, we aimed to explore the role and molecular mechanism of Dyrk1A in apoptosis. METHODS: Cell Counting Kit-8 (CCK8), flow cytometry, and TdT-mediated dUTP Nick-End Labeling (TUNEL) were used to check apoptosis. The cells, transfected with Dyrk1A or/and ASF with Bcl-x minigene, were used to assay Bcl-x expression by RT-PCR and Western blots. Co-immunoprecipitation, autoradiography, and immunofluorescence were conducted to check the interaction of ASF and Dyrk1A. Gene set enrichment analysis (GSEA) of apoptosis-related genes was performed in mice overexpressing Dyrk1A (TgDyrk1A) and AD model 5xFAD mice. RESULTS: Dyrk1A promoted Bcl-xS expression and apoptosis. Splicing factor ASF promoted Bcl-x exon 2b inclusion, leading to increased Bcl-xL expression. Dyrk1A suppressed ASF-mediated Bcl-x exon 2b inclusion via phosphorylation. The C-terminus deletion of Dyrk1A facilitated its binding and kinase activity to ASF. Moreover, Dyrk1a1-483 further suppressed the ASF-mediated Bcl-x exon 2b inclusion and aggravated apoptosis. The truncated Dyrk1A, increased Bcl-xS, and enrichment of apoptosis-related genes was observed in the brain of 5xFAD mice. CONCLUSIONS: We speculate that increased Dyrk1A and truncated Dyrk1A may aggravate neuronal apoptosis by decreasing the ratio of Bcl-xL/Bcl-xS via phosphorylating ASF in AD.

Partly recovery and compensation in anterior cingulate cortex after SSRI treatment-evidence from multi-voxel pattern analysis over resting state fMRI in depression.

BACKGROUND: Anterior cingulate cortex (ACC) plays an essential role in the pathophysiology of major depressive disorder (MDD) and its treatment. However, it's still unclear whether the effects of disease and antidepressant treatment on ACC perform diversely in neural mechanisms. METHODS: Fifty-nine MDD patients completed resting-state fMRI scanning twice at baseline and after 12-week selective serotonin reuptake inhibitor (SSRI) treatment, respectively in acute state and remission state. Fifty-nine demographically matched healthy controls were enrolled. Using fractional amplitude of low-frequency fluctuation (fALFF) in ACC as features, we performed multi-voxel pattern analysis over pretreatment MDD patients vs health control (HC), and over pretreatment MDD patients vs posttreatment MDD patients. RESULTS: Discriminative regions in ACC for MDD impairment and changes after antidepressants were obtained. The intersection set and difference set were calculated to form ACC subregions of recovered, unrecovered and compensative, respectively. The recovered ACC subregion mainly distributed in rostral ACC (80 %) and the other two subregions had nearly equal distribution over dorsal ACC and rostral ACC. Furthermore, only the compensative subregion had significant changed functional connectivity with cingulo-opercular control network (CON) after antidepressant treatment. LIMITATIONS: The number of subjects was relatively small. The results need to be validated with larger sample sizes and multisite data. CONCLUSIONS: This finding suggested that the local function of ACC was partly recovered on regulating emotion after antidepressant by detecting the common subregional targets of depression impairment and antidepressive effect. Besides, changed fALFF in the compensative ACC subregion and its connectivity with CON may partly compensate for the cognition deficits.

Sox11b regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish.

The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development. However, its function in retina regeneration remains elusive. Here we report that Sox11b, a zebrafish Sox11 homolog, regulates the migration and fate determination of Müller glia-derived progenitors (MGPCs) in an adult zebrafish model of mechanical retinal injury. Following a stab injury, the expression of Sox11b was induced in proliferating MGPCs in the retina. Sox11b knockdown did not affect MGPC formation at 4 days post-injury, although the nuclear morphology and subsequent radial migration of MGPCs were altered. At 7 days post-injury, Sox11b knockdown resulted in an increased proportion of MGPCs in the inner retina and a decreased proportion of MGPCs in the outer nuclear layer, compared with controls. Furthermore, Sox11b knockdown led to reduced photoreceptor regeneration, while it increased the numbers of newborn amacrines and retinal ganglion cells. Finally, quantitative polymerase chain reaction analysis revealed that Sox11b regulated the expression of Notch signaling components in the retina, and Notch inhibition partially recapitulated the Sox11b knockdown phenotype, indicating that Notch signaling functions downstream of Sox11b. Our findings imply that Sox11b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish, which may have critical implications for future explorations of retinal repair in mammals.

Lactic acid bacteria promoted soil quality and enhanced phytoextraction of Cd and Zn by mustard: A trial for bioengineering of toxic metal contaminated mining soils.

Microbial-assisted phytoremediation provides a green approach for remediation of metal contaminated soils. However, the impacts of mono and co-applications of lactic acid bacteria (LAB) on soil biochemical properties and phytoavailability of toxic metals in contaminated mining soils have not yet been sufficiently examined. Consequently, here we studied the effects of Lactobacillus plantarum (P), Lactobacillus acidophilus (A), and Lactobacillus rhamnosus (R) applications alone and in combination on soil enzyme activities and bioavailability and uptake of Cd and Zn by mustard (Brassica juncea) in a smelter-contaminated soil under greenhouse conditions. Among the studied bacteria, P was the most tolerant to Cd-and-Zn contamination. As compared to control, R increased the fresh and dry weight of mustard plants by 53.5% and 63.2%, respectively. Co-application of P + A increased the chlorophyll content by 28.6%, as compared to control. Addition of LAB to soil increased the activity of soil urease, alkaline phosphatase and ß-D glucosidase increased by 1.86-fold (P + R), 1.80-fold (R) and 55.16% (P + R), respectively. Application of P + A + R enhanced catalase activity (19.3%) and superoxide dismutase activity (51.2%), while addition of A alone increased peroxidase activity (POD: 15.7%). Addition of P alone and together with A (P + A) enhanced Cd and Zn phytoextraction by mustard shoots up to 51.5% and 52.5%, respectively. We conclude that the single and/or co-application of LAB decreased soil pH, promoted plant growth, antioxidant and enzyme activities, and enhanced the phytoavailability of Cd and Zn in the studied contaminated soil. These findings might be an aid for enhancing the phytoremediation of Cd and Zn using LAB and mustard as a bioenergy crop, which may offer new ideas for field treatment of toxic metals contaminated soils.

Integrated analyses reveal evolutionarily conserved and specific injury response genes in dorsal root ganglion.

Rodent dorsal root ganglion (DRG) is widely used for studying axonal injury. Extensive studies have explored genome-wide profiles on rodent DRGs under peripheral nerve insults. However, systematic integration and exploration of these data still be limited. Herein, we re-analyzed 21 RNA-seq datasets and presented a web-based resource (DRGProfile). We identified 53 evolutionarily conserved injury response genes, including well-known injury genes (Atf3, Npy and Gal) and less-studied transcriptional factors (Arid5a, Csrnp1, Zfp367). Notably, we identified species-preference injury response candidates (e.g. Gpr151, Lipn, Anxa10 in mice; Crisp3, Csrp3, Vip, Hamp in rats). Temporal profile analysis reveals expression patterns of genes related to pre-regenerative and regenerating states. Finally, we found a large sex difference in response to sciatic nerve injury, and identified four male-specific markers (Uty, Eif2s3y, Kdm5d, Ddx3y) expressed in DRG. Our study provides a comprehensive integrated landscape for expression change in DRG upon injury which will greatly contribute to the neuroscience community.

The clinical value of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and D-dimer-to-fibrinogen ratio for predicting pneumonia and poor outcomes in patients with acute intracerebral hemorrhage.

Background: This study aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and D-dimer-to-fibrinogen ratio (DFR) as predictors of pneumonia and poor outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We retrospectively examined patients with acute ICH treated in our institution from May 2018 to July 2020. Patient characteristics, laboratory testing data, radiologic imaging data, and 90-day outcomes were recorded and analyzed. Results: Among the 329 patients included for analysis, 183 (55.6%) developed pneumonia. Systolic blood pressure, initial hematoma volume, D-dimer concentration, NLR, PLR, DFR, and white blood cell, platelet, neutrophil, and lymphocyte counts at admission were significantly higher in patients who developed pneumonia than in those who did not; however, the Glasgow coma scale (GCS) score at admission was significantly lower in pneumonia patients compared with non-pneumonia patients (all P <0.05). Multivariate logistic regression showed that the NLR and PLR were independent predictors of pneumonia, and the NLR and DFR were independent predictors of poor 90-day outcomes (modified Rankin scale score 4-6). Conclusion: The NLR and PLR were independent predictors of pneumonia and the NLR and DFR were independent predictors of poor 90-day outcomes. The NLR, PLR, and DFR can provide prognostic information about acute ICH patients.

Corrigendum: New Prediction Models of Functional Outcome in Acute Intracerebral Hemorrhage: The dICH Score and uICH Score.

[This corrects the article DOI: 10.3389/fneur.2021.655800.].

High-throughput transcriptome sequencing reveals the key stages of cardiovascular development in zebrafish embryos.

BACKGROUND: The cardiovascular developmental process is a tightly regulated network involving multiple genes. The current understanding of the molecular mechanism behind cardiovascular development is insufficient and requires further research. RESULTS: Transcriptome sequencing of three developmental stages in zebrafish embryos was performed and revealed three key cardiovascular developmental stages. Then, the differentially expressed genes (DEGs) involved in cardiovascular development were screened out. The three developmental stages were 18 (T1), 24 (T2), and 42 h post fertilization (hpf) (T3), and the three stages were confirmed by detecting differences in expression between cardiomyocyte and endothelial marker genes (cmlc2, fli1) using in situ hybridization, which represents the characteristics of cardiovascular development. Thousands of DEGs were identified using transcriptome analysis. Of them, 2605 DEGs were in T1-vs-T2, including 2003 up-regulated and 602 down-regulated genes, 6446 DEGs were in T1-vs-T3, consisting of 4608 up-regulated and 1838 down-regulated genes, and 3275 DEGs were in T2-vs-T3, including 2420 up-regulated and 855 down-regulated genes. There were 644 common DEGs and 167 common five-fold higher differentially expressed genes (HDEGs) identified, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Significant differences was observed in the levels of gene expression among different developmental stages in multiple GO terms and KEGG pathways, such as cell migration to the midline involved in heart development, cardiovascular system development, circulatory system process for biological processes of GO terms; and cardiac muscle contraction, adrenergic signaling in cardiomyocytes for KEGG pathways. These results demonstrated that these three stages were important period for the development of the cardiovascular system. Lastly, we used quantitative real-time PCR (qPCR) to validate the reliability of RNA-sequencing by selecting 21 DEGs. CONCLUSIONS: These results demonstrated that these three stages represented the important periods for cardiovascular system development of zebrafish and some candidate genes was obtained and provided a solid foundation for additional functional studies of the DEGs.

The Expression and Function of lincRNA-154324 and the Adjoining Protein-Coding Gene vmp1 in the Caudal Fin Regeneration of Zebrafish.

Caudal fin regeneration is regulated by a variety of mechanisms, but the role of long non-coding RNA (lncRNA) has rarely been studied. The present study aimed to describe the landscape of lncRNAs during caudal fin regeneration using whole transcriptome sequencing, and then to conduct a functional study on the target lncRNAs using real-time fluorescent quantitative PCR (RT-qPCR), in situ hybridization, and the CRISPR/Cas9 method for lncRNA gene knockout. The results of the transcriptome sequencing showed that a total of 381 lncRNAs were differentially expressed, among which ENSDART00000154324 (lincRNA-154324) was found to be highly related to caudal fin regeneration, and thus it was chosen as the target lncRNA for the subsequent functional study. The results regarding the temporal and spatial expression of lincRNA-154324 and the gene knockout results from CRISPR/Cas9 indicated that lincRNA-154324 is involved in the caudal fin regeneration of zebrafish. Importantly, we serendipitously discovered that the cis correlation coefficient between lincRNA-154324 and its neighboring gene vacuole membrane protein 1 (vmp1) is extremely high, and they are essential for the process of caudal fin regeneration. Moreover, studies have found that vmp1 plays an important role in protein secretion, organelle formation, multicellular development, and autophagy. Collectively, our result may provide a framework for the identification and analysis of lncRNAs involved in the regeneration of the zebrafish caudal fin.

Context-dependent effects of inflammation on retina regeneration.

Inflammation is required for the proliferation of Müller glia (MG) into multipotent progenitors (MGPCs) in the injured fish and avian retinas. However, its function in retina regeneration has not been fully understood. Here we investigated the role of inflammation in three different retinal regeneration paradigms in zebrafish (stab-injury, NMDA-injury and insulin treatment). We first show that different types of immune cells and levels of inflammatory cytokines were found in the retinas of these paradigms. Though zymosan injection alone was insufficient to induce MG proliferation in the uninjured retina, immune suppression significantly inhibited MGPC formation in all three paradigms. Enhancing inflammation promoted MGPC formation after stab-injury, while exhibiting a context-dependent role in the NMDA or insulin models. We further show that proper levels of inflammation promoted MG reprogramming and cell cycle re-entry after stab- or NMDA-injury, but excessive inflammation also suppressed MG proliferation in the latter model. Finally, inflammation differentially affected neuronal regeneration in various injury paradigms. Our study reveals the complex and context-dependent role of inflammation during retinal repair in fish and suggests accurate inflammation management may be crucial for successful retina regeneration in mammals.

Uncovering a Distinct Gene Signature in Endothelial Cells Associated With Contrast Enhancement in Glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most aggressive and lethal type of brain tumors. Magnetic resonance imaging (MRI) has been commonly used for GBM diagnosis. Contrast enhancement (CE) on T1-weighted sequences are presented in nearly all GBM as a result of high vascular permeability in glioblastomas. Although several radiomics studies indicated that CE is associated with distinct molecular signatures in tumors, the effects of vascular endothelial cells, the key component of blood brain barrier (BBB) controlling vascular permeability, on CE have not been thoroughly analyzed. METHODS: Endothelial cell enriched genes have been identified using transcriptome data from 128 patients by a systematic method based on correlation analysis. Distinct endothelial cell enriched genes associated with CE were identified by analyzing difference of correlation score between CE-high and CE-low GBM cases. Immunohistochemical staining was performed on in-house patient cohort to validate the selected genes associated with CE. Moreover, a survival analysis was conducted to uncover the relation between CE and patient survival. RESULTS: We illustrated that CE is associated with distinct vascular molecular imprints characterized by up-regulation of pro-inflammatory genes and deregulation of BBB related genes. Among them, PLVAP is up-regulated, whereas TJP1 and ABCG2 are down-regulated in the vasculature of GBM with high CE. In addition, we found that the high CE is associated with poor prognosis and GBM mesenchymal subtype. CONCLUSION: We provide an additional insight to reveal the molecular trait for CE in MRI images with special focus on vascular endothelial cells, linking CE with BBB disruption in the molecular level. This study provides a potential new direction that may be applied for the treatment optimization based on MRI features.

New Prediction Models of Functional Outcome in Acute Intracerebral Hemorrhage: The dICH Score and uICH Score.

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH. Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score. Results: This study included 76 patients (23.3%) with hematoma expansion and 61 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes. Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH.

Functional impairment-based segmentation of anterior cingulate cortex in depression and its relationship with treatment effects.

In major depressive disorder (MDD), the anterior cingulate cortex (ACC) is widely related to depression impairment and antidepressant treatment response. The multiplicity of ACC subdivisions calls for a fine-grained investigation of their functional impairment and recovery profiles. We recorded resting state fMRI signals from 59 MDD patients twice before and after 12-week antidepressant treatment, as well as 59 healthy controls (HCs). With functional connectivity (FC) between each ACC voxel and four regions of interests (bilateral dorsolateral prefrontal cortex [DLPFC] and amygdalae), subdivisions with variable impairment were identified based on groups' dissimilarity values between MDD patients before treatment and HC. The ACC was subdivided into three impairment subdivisions named as MedialACC, DistalACC, and LateralACC according to their dominant locations. Furthermore, the impairment pattern and the recovery pattern were measured based on group statistical analyses. DistalACC impaired more on its FC with left DLPFC, whereas LateralACC showed more serious impairment on its FC with bilateral amygdalae. After treatment, FCs between DistalACC and left DLPFC, and between LateralACC and right amygdala were normalized while impaired FC between LateralACC and left amygdala kept dysfunctional. Subsequently, FC between DistalACC and left DLPFC might contribute to clinical outcome prediction. Our approach could provide an insight into how the ACC was impaired in depression and partly restored after antidepressant treatment, from the perspective of the interaction between ACC subregions and critical frontal and subcortical regions.

Investigation of bioactivities of Taxus chinensis, Taxus cuspidata, and Taxus × media by gas chromatography-mass spectrometry.

Taxus species have attracted much attention for their potency in cancer treatment. However, investigating the bioactivities of Taxus species is a complex task, due to their diversity, slow growth, and endangered state. The most important Taxus species in China are Taxus chinensis (T. chinensis), Taxus cuspidata (T. cuspidata), and Taxus × media (T. media), which mainly grow in the northeastern region. This article probes deep into the differences among the leaves of T. chinensis, T. cuspidata, and T. media, with the aid of gas chromatography-mass spectrometry (GC-MS). Through GC-MS, 162 compounds were detected in the samples and found to contain 35 bioactive metabolites. On this basis, 20 metabolites with significant bioactivities (antibiotic, antioxidant, anticancer, and antiaging effects) were identified via unsupervised learning of principal component analysis and supervised learning of partial least squares-discriminant analysis. The results show that T. media has the most prominent antibiotic, antioxidant, and anticancer effects, while T. cuspidata has the most diverse and abundant metabolites that slow down aging.

Noncontrast Computed Tomography Markers as Predictors of Revised Hematoma Expansion in Acute Intracerebral Hemorrhage.

Background Noncontrast computed tomography (NCCT) markers are the emerging predictors of hematoma expansion in intracerebral hemorrhage. However, the relationship between NCCT markers and the dynamic change of hematoma in parenchymal tissues and the ventricular system remains unclear. Methods and Results We included 314 consecutive patients with intracerebral hemorrhage admitted to our hospital from July 2011 to May 2017. The intracerebral hemorrhage volumes and intraventricular hemorrhage (IVH) volumes were measured using a semiautomated, computer-assisted technique. Revised hematoma expansion (RHE) was defined by incorporating the original definition of hematoma expansion into IVH growth. Receiver operating characteristic curve analysis was used to compare the performance of the NCCT markers in predicting the IVH growth and RHE. Of 314 patients in our study, 61 (19.4%) had IVH growth and 93 (23.9%) had RHE. After adjustment for potential confounding variables, blend sign, black hole sign, island sign, and expansion-prone hematoma could independently predict IVH growth and RHE in the multivariate logistic regression analysis. Expansion-prone hematoma had a higher predictive performance of RHE than any single marker. The diagnostic accuracy of RHE in predicting poor prognosis was significantly higher than that of hematoma expansion. Conclusions The NCCT markers are independently associated with IVH growth and RHE. Furthermore, the expansion-prone hematoma has a higher predictive accuracy for prediction of RHE and poor outcome than any single NCCT marker. These findings may assist in risk stratification of NCCT signs for predicting active bleeding.

Expression analysis of Hsp90α and cytokines in zebrafish caudal fin regeneration.

Zebrafish (Danio rerio) is an ideal model organism for exploring the ability and mechanism of tissue regeneration in the vertebrate. However, the specific cellular and molecular mechanism of caudal fin regeneration in zebrafish remains largely unclear. Therefore, we first confirmed the crucial period of fin regeneration in adult zebrafish by morphological and histological analysis. Then we performed RNA-Seq analysis of the caudal fin regeneration at three key stages, which provided some clues for exploring the mechanism of caudal fin regeneration. Moreover, we also determined the expressions of inflammatory cytokines IL-1ß, IL-6, IL-8, IL-10, TGF-ß, and the immune-related pathway JAK2α and STAT1b in the caudal fin of zebrafish following fin amputation by quantitative real time PCR (qPCR). Particularly, Hsp90α expression at mRNA and protein level determined by qPCR and Western blotting, respectively, and whole-mount in situ hybridization of Hsp90α were also performed in this study. The results showed that inflammatory cytokines were mainly expressed in the early period of caudal fin regeneration (1-3 days post amputation, dpa), indicating that fish immune system was involved in the fin regeneration. Furthermore, the high expression of Hsp90α in the vicinity of blastema and blood vessels of the regenerating fin suggests that Hsp90α may play a role in the initiation and promotion of caudal fin regeneration. Overall, our results provide a framework for further understanding the cellular and molecular mechanism in caudal fin regeneration.

Hematoma Ventricle Distance on Computed Tomography Predicts Poor Outcome in Intracerebral Hemorrhage.

OBJECTIVE: To investigate the relationship between hematoma ventricle distance (HVD) and clinical outcome in patients with intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled consecutive patients with ICH in a tertiary academic hospital between July 2011 and April 2018. We retrospectively reviewed images for all patients receiving a computed tomography (CT) within 6 h after onset of symptoms and at least one follow-up CT scan within 36 h. The minimum distance of hematoma border to nearest ventricle was measured as HVD. Youden index was used to evaluate the cutoff of HVD predicting functional outcome. Logistic regression model was used to assess the HVD data and clinical poor outcome (modified Rankin Scale 4-6) at 90 days. RESULTS: A total of 325 patients were included in our final analysis. The median HVD was 2.4 mm (interquartile range, 0-5.7 mm), and 119 (36.6%) patients had poor functional outcome at 3 months. After adjusting for age, admission Glasgow coma scale, intraventricular hemorrhage, baseline ICH volume, admission systolic blood pressure, blood glucose, hematoma expansion, withdrawal of care, and hypertension, HVD ≤ 2.5 mm was associated with increased odds of clinical poor outcome [odd ratio, 3.59, (95%CI = 1.72-7.50); p = 0.001] in multivariable logistic regression analysis. CONCLUSION: Hematoma ventricle distance allows physicians to quickly select and stratify patients in clinical trials and thereby serve as a novel and useful addition to predict ICH prognosis.

Long non­coding RNA NONHSAT143692.2 is involved in oxidative DNA damage repair in the lens by regulating the miR­4728­5p/OGG1 axis.

Age­related cataract (ARC) is the leading cause of blindness worldwide. Oxidative DNA damage is a biochemical feature of ARC pathogenesis. The present study investigated the role of long non­coding RNAs in the DNA repair of oxidative damage, partially the regulation of the DNA repair gene, 8­oxoguanine DNA glycosylase (OGG1), in lens affected by ARC. The ogg1 mutant zebrafish model was constructed to verify the role of ogg1 in the lens. A high­throughput lncRNA profiling was performed on human lens epithelial cells (LECs) following oxidative stress. The lncRNAs with the OGG1 target gene were analyzed for possible differentiated expression levels. The lens capsule samples of patients with ARC were collected to further verify the screening results. lncRNA was then overexpressed and knocked down in LECs to observe cell proliferation and apoptosis. The association between lncRNA, miRNA and the OGG1 mRNA 3'UTR were analyzed. The ogg1 mutant zebrafish developed more severe lens lesions following oxidative challenge. lncRNA NONHSAT143692.2 was distinctly expressed in various disease models. The knockdown of NONHSAT143692.2 downregulated the expression of OGG1 mRNA (P<0.001) and OGG1 protein (P<0.001), aggravated oxidative damage to LECs, increased apoptosis (P<0.001) and decreased cell proliferation (P<0.01). The overexpression of NONHSAT143692.2 reversed the above­mentioned outcomes. miR­4728­5p was predicted to bind to NONHSAT143692.2 and OGG1 mRNA 3'UTR. The overexpression of miR­4728­5p downregulated the expression of NONHSAT143692.2 (P<0.001), OGG1 mRNA (P<0.001) and OGG1 protein (P<0.001). The knockdown of miR­4728­5p reversed the above­mentioned outcomes. Overall, the findings of the present study demonstrate that the NONHSAT143692.2/miR­4728­5p/OGG1 axis may play an important role in the development of ARC. This novel concept may provide new insight into the molecular diagnosis and treatment of ARC.