Adaptive radiation in Orinus, an endemic alpine grass of the Qinghai-Tibet Plateau, based on comparative transcriptomic analysis.

The species of Orinus (Poaceae) are important alpine plants with a variety of phenotypic traits and potential usages in molecular breeding toward drought-tolerant forage crops. However, the genetic basis of evolutionary adaption and diversification in the genus is still unclear. In the present study, we obtained transcriptomes for the two most divergent species, O. thoroldii and O. kokonoricus, using the Illumina platform and de novo assembly. In total, we generated 23,029 and 24,086 unigenes with N50 values of 1188 and 1203 for O. thoroldii and O. kokonoricus respectively, and identified 19,005 pairs of putative orthologs between the two species of Orinus. For these orthologs, estimations of non-synonymous/synonymous substitution rate ratios indicated that 568 pairs may be under strongly positive selection (Ka/Ks > 1), and Gene Ontogeny (GO) enrichment analysis revealed that significantly enriched pathways were in DNA repair and resistance to abiotic stress. Meanwhile, the divergence times of species between O. thoroldii and O. kokonoricus occurred 3.2 million years ago (Mya), and the recent evolutionary branch is an allotetraploid species, Cleistogenes songorica. We also detected a Ks peak of ∼0.60 for Orinus. Additionally, we identified 188 pairs of differentially expressed genes (DEGs) between the two species of Orinus, which were significantly enrich in stress resistance and lateral root development. Thus, we considered that the species diversification and evolutionary adaption of this genus was initiated by environmental selection, followed by phenotypic differentiation, finally leading to niche separation in the Qinghai-Tibet Plateau.

Establishment and Validation of an Integrated Model to Predict Postoperative Recurrence in Patients With Atypical Meningioma.

BACKGROUND: This study aims to establish an integrated model based on clinical, laboratory, radiological, and pathological factors to predict the postoperative recurrence of atypical meningioma (AM). MATERIALS AND METHODS: A retrospective study of 183 patients with AM was conducted. Patients were randomly divided into a training cohort (n = 128) and an external validation cohort (n = 55). Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, time-dependent receiver operating characteristic (ROC) curve analysis, and evaluation of clinical usage were used to select variables for the final nomogram model. RESULTS: After multivariable Cox analysis, serum fibrinogen >2.95 g/L (hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.05-5.63; p = 0.039), tumor located in skull base (HR, 6.59; 95% CI, 2.46-17.68; p < 0.001), Simpson grades III-IV (HR, 2.73; 95% CI, 1.01-7.34; p = 0.047), tumor diameter >4.91 cm (HR, 7.10; 95% CI, 2.52-19.95; p < 0.001), and mitotic level ≥4/high power field (HR, 2.80; 95% CI, 1.16-6.74; p = 0.021) were independently associated with AM recurrence. Mitotic level was excluded after LASSO analysis, and it did not improve the predictive performance and clinical usage of the model. Therefore, the other four factors were integrated into the nomogram model, which showed good discrimination abilities in training cohort (C-index, 0.822; 95% CI, 0.759-0.885) and validation cohort (C-index, 0.817; 95% CI, 0.716-0.918) and good match between the predicted and observed probability of recurrence-free survival. CONCLUSION: Our study established an integrated model to predict the postoperative recurrence of AM.

Preoperative serum lactate dehydrogenase level predicts progression and prognosis in patients with glioma.

BACKGROUND: To evaluate the value of serum Lactate Dehydrogenase (LDH) level in predicting recurrence and the overall survival (OS) of glioma patients. MATERIALS AND METHODS: A total number of 216 patients with glioma in our institution were retrospectively recruited to analyze the relationship between preoperative serum LDH level and prognosis. RESULTS: Overall, the median age of patients was 46.0 (31.0-57.0) years old; 53.7% (116 of 216) of the enrolled patients were male. Multivariate analysis revealed that serum LDH level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.96-0.98, P < 0.001) and World Health Organization (WHO) grade (grade II: OR = 19.64, 95%CI = 5.56-69.35, P < 0.001; grade III: OR =1 9.50, 95%CI = 7.08-53.73, P < 0.001; grade IV: OR = 15.23, 95%CI = 4.94-46.97, P < 0.001) were significant and independent of 1-year Progression-free survival (PFS) after adjusting for confounders. The predictive performance of serum LDH level was represented with area under curve (AUC) = 0.741, 95%CI = 0.677-0.798. Multivariate Cox analysis revealed that LDH level (hazard ratio [HR] = 2.56, 95%CI = 1.59-4.15, P < 0.001) and WHO grade (grade II: HR = 4.58, 95%CI = 0.56-37.23, P = 0.155; grade III: HR = 16.35, 95%CI = 2.16-123.80, P = 0.007; grade IV: HR = 42.13, 95%CI = 5.83-304.47, P < 0.001) remained associated with survival at 2-year follow-up. At 3-year follow-up, lymphocyte count (HR = 0.68, 95%CI = 0.51-0.91, P = 0.008), LDH level (HR = 2.21, 95%CI = 1.40-3.49, P = 0.001), and WHO grade (grade II: HR = 1.44, 95%CI = 0.44-4.68, P = 0.543; grade III: HR = 4.99, 95%CI = 1.68-14.87, P = 0.004; grade IV: HR = 16.96, 95%CI = 6.13-46.93, P < 0.001) remained associated with survival in multivariate Cox analysis. CONCLUSION: Our study demonstrated that preoperative serum LDH level could serve as a reliable indicator for predicting prognosis of glioma patients. Further multicenter studies are still required to verify our findings.

The Relationship Between Peritumoral Brain Edema and the Expression of Vascular Endothelial Growth Factor in Vestibular Schwannoma.

Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression. Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated. Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p < 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p < 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p < 0.001) and VEGF and EI (r = 0.876, p < 0.001). Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.

New lymphatic cell formation is associated with damaged brain tissue clearance after penetrating traumatic brain injury.

We characterized the tissue repair response after penetrating traumatic brain injury (pTBI) in this study. Seventy specific pathogen-free Kunming mice were randomly divided into the following groups: normal control, 1, 3, 7, 15, 21, and 30 days after pTBI. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were performed to examine and monitor brain tissue morphology, and the distribution and expression of lymphatic-specific markers lymphatic vessel endothelial receptor-1 (LYVE-1), hematopoietic precursor cluster of differentiation 34 (CD34) antigen, and Prospero-related homeobox-1 (PROX1) protein. H&E staining revealed that damaged and necrotic tissues observed on day 1 at and around the injury site disappeared on day 7, and there was gradual shrinkage and disappearance of the lesion on day 30, suggesting a clearance mechanism. We explored the possibility of lymphangiogenesis causing this clearance as part of the post-injury response. Notably, expression of lymphangiogenesis markers LYVE-1, CD34, and PROX1 was detected in damaged mouse brain tissue but not in normal tissue. Moreover, new lymphatic cells and colocalization of LYVE-1/CD34 and LYVE-1/PROX1 were also observed. Our findings of the formation of new lymphatic cells following pTBI provide preliminary insights into a post-injury clearance mechanism in the brain. Although we showed that lymphatic cells are implicated in brain tissue repair, further research is required to clarify the origin of these cells.

Glioblastoma in a female neurofibromatosis 1 patient without IDH1, BRAF V600E, and TERT promoter mutations: A case report.

RATIONALE: Glioblastoma is the most lethal and common malignant brain tumor but rare in patients with neurofibromatosis type 1. The clinical findings and pathological findings with gene signatures in female patients have not been well clarified. PATIENT CONCERNS: A 51-year-old female patient complained of headache and left limb weakness lasting for 20 days. The patient underwent a cesarean section 20 years ago and hysterectomy 1 year ago because of uterine leiomyomas. Multiple café-au-lait spots and neurofibromas were found over patient's chest, neck, back, and arms. The myodynamia of left distant and proximate epipodite were grade 0 and grade 1 respectively. The myodynamia of lower left limb was grade 3. DIAGNOSES: Magnetic resonance imaging revealed a malignant lesion which was most likely a glioblastoma in the right temporo-parietal lobe, approximately 5.6 × 5.9 × 6.9 cm in size with a rounded boundary. INTERVENTIONS: A right temporo-parietal craniotomy was performed to resect the space-occupying lesion for gross total removal. Then, the patient received concurrent chemoradiotherapy. Histological examination confirmed a glioblastoma without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. OUTCOMES: After surgery, the headache was relieved and the muscular strength of left limbs did improve. After receiving the standard treatment regimen, the patient was alive at 13 months follow-up. LESSONS: This is the first reported glioblastoma in female neurofibromatosis type 1 patient without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. Tumors in adult patients with these signatures were less aggressive with well-circumscribed border and had long-term survivals which strengthened the evidence that these patients may comprise a unique subset in glioblastoma.

Serum Inflammatory Biomarkers Contribute to the Prognosis Prediction in High-Grade Glioma.

BACKGROUND: To evaluate the prognostic value of serum inflammatory biomarkers and develop a risk stratification model for high-grade glioma (HGG) patients based on clinical, laboratory, radiological, and pathological factors. MATERIALS AND METHODS: A retrospective study of 199 patients with HGG was conducted. Patients were divided into a training cohort (n = 120) and a validation cohort (n = 79). The effects of potential associated factors on the overall survival (OS) time were investigated and the benefits of serum inflammatory biomarkers in improving predictive performance was assessed. Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, and support vector machines (SVM) were used to select variables for the final nomogram model. RESULTS: After multivariable Cox, LASSO, and SVM analysis, in addition to 3 other clinico-pathologic factors, platelet-to-lymphocyte ratio (PLR) >144.4 (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.25-3.38; P = 0.005) were left for constructing the predictive model. The model with PLR exhibited a better predictive performance than that without them in both cohorts. The nomogram based on the model showed an excellent ability of discrimination in the entire cohort (C-index, 0.747; 95%CI, 0.706-0.788). The calibration curves showed good consistency between the predicted and observed survival probability. CONCLUSION: Our study confirmed the prognostic value of serum inflammatory biomarkers including PLR and established a comprehensive scoring system for the OS prediction in HGG patients.

Relationship Between Pituitary Adenoma Consistency and Extent of Resection Based on Tumor/Cerebellar Peduncle T2-Weighted Imaging Intensity (TCTI) Ratio of the Point on Preoperative Magnetic Resonance Imaging (MRI) Corresponding to the Residual Point on Postoperative MRI.

BACKGROUND Controversies exist in imaging modalities for predicting adenoma consistency. In this study, we proposed a method of predicting consistency by magnetic resonance T2-sequence imaging based on adenoma to cerebellar peduncle signal (TCTI) ratio. MATERIAL AND METHODS Between January 2013 and May 2017, 191 consecutive patients with pituitary adenoma diagnosed at our institution were retrospectively studied. The consistency grade for each lesion was assigned. And the TCTI ratio based on preoperative and postoperative T2-weighted imaging was calculated. RESULTS The median TCTI ratio was 1.55, 1.28, and 1.25 for soft, fibrous, and hard adenomas, respectively. The differences were significant for all groups (p<0.001). A cutoff value of 1.38 for soft adenomas was found to be 80.2% sensitive and 88.7% specific. The median ratio of the outermost layer of residual tumor was 1.25 (SD±0.408, 95% CI 1.27-1.42). It was less than that ratio of the upper, lower quarter, and middle region of adenoma, respectively, and the inter-group differences were all statistically significant with p≤0.001. The extent of resection for the soft group was significantly greater than that of the hard group (85.3% vs. 70.6%, p=0.011). Analysis of Variance (ANOVA) revealed that the consistency grade was the influencing factor of degree of resection. p=0.003. CONCLUSIONS The TCTI ratio showed a good correlation with pituitary adenoma consistency. We also determined the optimal ratio of the residual adenoma.

[Effects of biochar addition on enzyme activity and fertility in paddy soil after six years]. / 施用生物炭6å¹´åŽå¯¹ç¨»ç”°åœŸå£¤é ¶æ´»æ€§åŠè‚¥åŠ›çš„å½±å“.

A field experiment was conducted to examine the effects on soil fertility and enzyme activities in paddy field after six years of one-split rice straw-derived biochar [0 (BC0), 7.5(BC1), 15(BC2), 22.5(BC3) t·hm-2] and rice straw (3.75 t·hm-2, STR) application. The results showed that soil organic carbon, available phosphorus and rapidly available potassium concentrations significantly increased, by 34.6%, 12.4% and 26.2%, respectively. Soil pH and soil bulk density were significantly reduced, but total nitrogen content had no significant difference compared with BC0. Biochar addition significantly increased the activities of soil urease and acid phosphatase. The soil fluorescein diacetate (FDA hydrolase) and arylsulfatase activity were inhibited to varying degrees. Among them, BC2 treatment increased soil urease activity by 36.5%. The soil acid phosphatase activity increased with the increases of biochar application rate, which was positively correlated with soil available phosphorus concentration. FDA hydrolase and urease activity had positive correlation with soil available potassium content, while soil acid phosphatase and arylsulfatase activity had positive correlation with soil bulk density. After six years, soil dehydrogenase and polyphenol oxidase activity significantly increased by 48.8% and 27.5%, respectively, while catalase activity significantly decreased when compared with control BC0. STR treatment increased activities of soil urease, FDA hydrolase, dehydrogenase, acid phosphatase and arylsulfatase significantly, while decreased the catalase and polyphenol oxidase activities by 23.4% and 15.9%, respectively.

Asiatic acid promotes p21(WAF1/CIP1) protein stability through attenuation of NDR1/2 dependent phosphorylation of p21(WAF1/ CIP1) in HepG2 human hepatoma cells.

Previous studies have suggested anti-tumor effects of asiatic acid in some human cancer cell lines. This agent is reported to increase the levels of p21WAF1/CIP1 in human breast cancer cell lines. However, the molecular mechanisms have not been established. Here we report that asiatic acid up-regulates p21WAF1/CIP1 protein expression but not the level of p21WAF1/CIP1 mRNA in HepG2 human hepatoma cells. Furthermore, we found that the asiatic acid induced increase of p21WAF1/CIP1 protein was associated with decreased phosphorylation (ser-146) of p21WAF1/CIP1. Knockdown of NDR1/2 kinase, which directly phosphorylates p21WAF1/CIP1 protein at ser-146 and enhances its proteasomal degradation, increased the levels of p21WAF1/CIP1 protein and eliminated the regulation of p21WAF1/ CIP1 stability by asiatic acid. At the same time, the expression of NDR1/2 kinase decreased during treatment with asiatic acid in HepG2 cells. Moreover, asiatic acid inhibited the proliferation of HepG2 cells, this being attenuated by knockdown of p21WAF1/CIP1. In conclusion, we propose that asiatic acid inhibits the expression NDR1/2 kinase and promotes the stability of p21WAF1/CIP1 protein through attenuating NDR1/2 dependent phosphorylation of p21WAF1/CIP1 in HepG2 cells.

A sandwich-type DNA biosensor based on electrochemical co-reduction synthesis of graphene-three dimensional nanostructure gold nanocomposite films.

A novel electrochemical DNA biosensor based on graphene-three dimensional nanostructure gold nanocomposite modified glassy carbon electrode (G-3D Au/GCE) was fabricated for detection of survivin gene which was correlated with osteosarcoma. The G-3D Au film was prepared with one-step electrochemical coreduction with graphite oxide and HAuCl4 at cathodic potentials. The active surface area of G-3D Au/GCE was 2.629cm(2), which was about 3.8 times compared to that of a Au-coated GCE under the same experimental conditions, and 8.8 times compared to a planar gold electrode with a similar geometric area. The resultant nanocomposites with high conductivity, electrocatalysis and biocompatibility were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). A "sandwich-type" detection strategy was employed in this electrochemical DNA biosensor and the response of this DNA biosensor was measured by CV and amperometric current-time curve detection. Under optimum conditions, there was a good linear relationship between the current signal and the logarithmic function of complementary DNA concentration in a range of 50-5000fM with a detection limit of 3.4fM. This new biosensor exhibited a fast amperometric response, high sensitivity and selectivity and has been used in a polymerase chain reaction assay of real-life sample with a satisfactory result.

Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway.

Coronary artery disease (CAD) is associated with high mortality and occurs via endothelial injury. Endothelial progenitor cells (EPCs) restore the integrity of the endothelium and protect it from atherosclerosis. In this study, we compared the expression of microRNAs (miRNAs) in EPCs in atherosclerosis patients and normal controls. We found that miR-221 expression was significantly up-regulated in patients compared with controls. We predicted and identified p21/Cdc42/Rac1-activated kinase 1 (PAK1) as a novel target of miR-221 in EPCs. We also demonstrated that miR-221 targeted a putative binding site in the 3'UTR of PAK1, and absence of this site was inversely associated with miR-221 expression in EPCs. We confirmed this relationship using a luciferase reporter assay. Furthermore, overexpression of miR-221 in EPCs significantly decreased EPC proliferation, in accordance with the inhibitory effects induced by decreased PAK1. Overall, these findings demonstrate that miR-221 affects the MEK/ERK pathway by targeting PAK1 to inhibit the proliferation of EPCs.