Meta-Analysis and Multiomics of a Chromosome Segment Substitution Line Reveal Candidate Genes Associated with Seed Hardness in Soybean.

Soybean seed hardness is a key trait that influences planting, nutritional quality, and postharvest processing, but its genetic and molecular mechanisms remain to be clarified. We used meta-analysis to detect 17 meta-quantitative trait locus (QTLs) for soybean seed hardness. We then identified a hard-seeded chromosome segment substitution line, R75, with fragments introduced from hard-seeded wild germplasm in four of the meta-QTL intervals. Observations of the seed coat ultrastructure revealed thicker palisade tissue in R75 than in its soft-seeded recurrent parent. Transcriptomics and proteomics of R75 and its recurrent parent revealed multiple candidate genes associated with seed hardness. Fifty-seven were located on homozygous introduced fragments, 26 in meta-QTL intervals, and one in both (Glyma.02G268600). Five initial candidates were selected for KASP marker development on the basis of their predicted functions and nonsynonymous SNPs. The selection efficiency of the markers was as high as 90% for nonhard lines and 43% for hard lines in the chromosome segment substitution line (CSSL) population.

Exploring the Functional Roles of Telomere Maintenance 2 in the Tumorigenesis of Glioblastoma Multiforme and Drug Responsiveness to Temozolomide.

Glioblastoma multiforme (GBM) is a grade IV human glioma. It is the most malignant primary central nervous system tumor in adults, accounting for around 15% of intracranial neoplasms and 40-50% of all primary malignant brain tumors. However, the median survival time of GBM patients is still less than 15 months, even after treatment with surgical resection, concurrent chemoradiotherapy, and adjuvant chemotherapy with temozolomide (TMZ). Telomere maintenance 2 (TELO2) mRNA is highly expressed in high-grade glioma patients, and its expression correlates with shorter survival outcomes. Hence, it is urgent to address the functional role of TELO2 in the tumorigenesis and TMZ treatment of GBM. In this study, we knocked down TELO2 mRNA in GBM8401 cells, a grade IV GBM, compared with TELO2 mRNA overexpression in human embryonic glial SVG p12 cells and normal human astrocyte (NHA) cells. We first analyzed the effect of TELO2 on the Elsevier pathway and Hallmark gene sets in GBM8401, SVG p12, and NHA via an mRNA array analysis. Later, we further examined and analyzed the relationship between TELO2 and fibroblast growth factor receptor 3, cell cycle progression, epithelial-mesenchymal transient (EMT), reactive oxygen species (ROS), apoptosis, and telomerase activity. Our data showed that TELO2 is involved in several functions of GBM cells, including cell cycle progression, EMT, ROS, apoptosis, and telomerase activity. Finally, we examined the crosstalk between TELO2 and the responsiveness of TMZ or curcumin mediated through the TELO2-TTI1-TTI2 complex, the p53-dependent complex, the mitochondrial-related complex, and signaling pathways in GBM8401 cells. In summary, our work provides new insight that TELO2 might modulate target proteins mediated through the complex of phosphatidylinositol 3-kinase-related kinases in its involvement in cell cycle progression, EMT, and drug response in GBM patients.

Risk factors of postoperative hydrocephalus following decompressive craniectomy for spontaneous intracranial hemorrhages and intraventricular hemorrhage.

INTRODUCTION: Hydrocephalus is a complication of spontaneous intracerebral hemorrhage; however, its predictive relationship with hydrocephalus in this patient cohort is not understood. Here, we evaluated the incidence and risk factors of hydrocephalus after craniectomy. METHODS: Retrospectively studied data from 39 patients in the same hospital from 2016/01 to 2020/12 and analyzed risk factors for hydrocephalus. The clinical data recorded included patient age, sex, timing of surgery, initial Glasgow Coma Scale score, intracerebral hemorrhage (ICH) score, alcohol consumption, cigarette smoking, medical comorbidity, and blood data. Predictors of patient outcomes were determined using Student t test, chi-square test, and logistic regression. RESULTS: We recruited 39 patients with cerebral herniation who underwent craniectomy for spontaneous supratentorial hemorrhage. Persistent hydrocephalus was observed in 17 patients. The development of hydrocephalus was significantly associated with the timing of operation, cigarette smoking, and alcohol consumption according to the Student t test and chi-square test. Univariate and multivariate analyses suggested that postoperative hydrocephalus was significantly associated with the timing of surgery (P = .031) and cigarette smoking (P = .041). DISCUSSION: The incidence of hydrocephalus in patients who underwent delayed operation (more than 4 hours) was lower than that in patients who underwent an operation after less than 4 hours. nonsmoking groups also have lower incidence of hydrocephalus. Among patients who suffered from spontaneous supratentorial hemorrhage and need to receive emergent craniectomy, physicians should be reminded that postoperative hydrocephalus followed by ventriculoperitoneal shunting may be necessary in the future.

Sparse phase retrieval using a physics-informed neural network for Fourier ptychographic microscopy.

In this paper, we report a sparse phase retrieval framework for Fourier ptychographic microscopy using the recently proposed principle of physics-informed neural networks. The phase retrieval problem is cast as training bidirectional mappings from the measured image space with random noise and the object space to be reconstructed, in which the image formation physics and convolutional neural network are integrated. Meanwhile, we slightly modify the mean absolute error loss function considering the signal characteristics. Two datasets are used to validate this framework. The results indicate that the proposed framework is able to reconstruct sparsely sampled data using a small aperture overlapping rate without additional data driving whereas conventional methods cannot.

Exploring the Mechanism of Adjuvant Treatment of Glioblastoma Using Temozolomide and Metformin.

Glioblastoma is the most frequent and lethal primary central nervous system tumor in adults, accounting for around 15% of intracranial neoplasms and 40-50% of all primary malignant brain tumors, with an annual incidence of 3-6 cases per 100,000 population. Despite maximum treatment, patients only have a median survival time of 15 months. Metformin is a biguanide drug utilized as the first-line medication in treating type 2 diabetes. Recently, researchers have noticed that metformin can contribute to antineoplastic activity. The objective of this study is to investigate the mechanism of metformin as a potential adjuvant treatment drug in glioblastoma. Glioblastoma cell lines U87MG, LNZ308, and LN229 were treated with metformin, and several cellular functions and metabolic states were evaluated. First, the proliferation capability was investigated using the MTS assay and BrdU assay, while cell apoptosis was evaluated using the annexin V assay. Next, a wound-healing assay and mesenchymal biomarkers (N-cadherin, vimentin, and Twist) were used to detect the cell migration ability and epithelial-mesenchymal transition (EMT) status of tumor cells. Gene set enrichment analysis (GSEA) was applied to the transcriptome of the metformin-treated glioblastoma cell line. Then, DCFH-DA and MitoSOX Red dyes were used to quantify reactive oxygen species (ROS) in the cytosol and mitochondria. JC-1 dye and Western blotting analysis were used to evaluate mitochondrial membrane potential and biogenesis. In addition, the combinatory effect of temozolomide (TMZ) with metformin treatment was assessed by combination index analysis. Metformin could decrease cell viability, proliferation, and migration, increase cell apoptosis, and disrupt EMT in all three glioblastoma cell lines. The GSEA study highlighted increased ROS and hypoxia in the metformin-treated glioblastoma cells. Metformin increased ROS production, impaired mitochondrial membrane potential, and reduced mitochondrial biogenesis. The combined treatment of metformin and TMZ had U87 as synergistic, LNZ308 as antagonistic, and LN229 as additive. Metformin alone or combined with TMZ could suppress mitochondrial transcription factor A, Twist, and O6-methylguanine-DNA methyltransferase (MGMT) proteins in TMZ-resistant LN229 cells. In conclusion, our study showed that metformin decreased metabolic activity, proliferation, migration, mitochondrial biogenesis, and mitochondrial membrane potential and increased apoptosis and ROS in some glioblastoma cells. The sensitivity of the TMZ-resistant glioblastoma cell line to metformin might be mediated via the suppression of mitochondrial biogenesis, EMT, and MGMT expression. Our work provides new insights into the choice of adjuvant agents in TMZ-resistant GBM therapy.

Flow-diverter stent to manage intracranial aneurysms: A single center experience.

BACKGROUND: Endovascular coil embolization is an important method for managing intracranial aneurysms. However, aneurysm coiling may fail or be insufficient in geographically difficult aneurysms. A flow-diverter stent (FDS) is an alternative in these difficult coiling aneurysms. Thus, this study reports the experience and outcome of FDS management of intracranial aneurysms. METHODS: Over 29 months, FDS treated 125 patients with 163 intracranial unruptured aneurysms. This study enrolled 31 men and 94 women, ranging from 17 to 81 years (mean, 58 years). Clinical data, aneurysm characteristics, and angiographic and clinical outcomes of patients treated by FDS were retrospectively assessed. RESULTS: The current study found 151 (93%) aneurysms in the internal carotid artery. Most aneurysms (n = 118; 72%) were small (<7 mm). The mean aneurysm size was 6.2 mm (range, 2-38 mm). Follow-up angiography was available in 53 patients with 74 aneurysms (mean, 13 months). Successful FDS deployment in an ideal position was found in 125 of 130 patients (96%). Complete obliteration (CO) was achieved in 58 aneurysms (78%) in the mean 13-month angiographic follow-up. Smaller aneurysms (<7 mm) had a CO tendency than larger aneurysms (p < 0.01) in midterm follow-up. Seven patients (5.6%) had intraprocedural complications (in-stent thrombosis, three patients; distal embolic, two patients; iatrogenic carotid-cavernous fistula, and subarachnoid hemorrhage, one patient). Two patients (1.6%) suffered from permanent procedure-related morbidity (n = 1) or mortality (n = 1). No late hemorrhagic events or stent displacement occurred during the follow-up period. CONCLUSION: Despite few procedural complications and some pieces of evidence of insufficient aneurismal treatment in a midterm angiographic follow-up, FDS was effective and safe in managing intracranial unruptured aneurysms, particularly in smaller aneurysms, which had better CO than larger ones.

Fabrication of MgO-Y2O3 Composite Nanopowders by Combining Hydrothermal and Seeding Methods.

In this study, the combination of hydrothermal technique and seed-doping method was conducted to coordinately control the formation of fine MgO-Y2O3 powders, which are promising mid-infrared materials applied to hypersonic aircraft windows due to their excellent infrared transmissions over wide regions. Y(NO3)3·6H2O, Mg(NO3)2·6H2O, Y2O3 seeds and MgO seeds were used as raw materials to prepare the MgO-Y2O3 composite powders (50:50 vol.%), and the influences of the seed contents and hydrothermal treatment temperatures on the final powders and hot-pressed ceramics were investigated by XRD, SEM and TEM techniques. The results show that powders with a seed content of 5% that are hydrothermally synthesized at 190 °C can present a better uniformity and dispersion with a particle size of ~125 nm. Furthermore, the ceramics prepared with the above powders displayed a homogenous two-phase microstructure, fewer pores and a fine grain size with Y2O3 of ~1 µm and MgO of ~620 nm. The present study may open an avenue for developing transparent ceramics based on MgO-Y2O3 nanopowders prepared by hydrothermal technique.

High-entropy R2O3-Y2O3-TiO2-ZrO2-Al2O3 glasses with ultrahigh hardness, Young's modulus, and indentation fracture toughness.

Glasses with high hardness, high Young's modulus, and high fracture toughness become crucial materials which are urgently needed in the protective covers for various electronic displays. Here, a paradigm is presented that the conceptual design of high-entropy materials is adaptable to high performance oxide glasses. We designed the multi-component glass compositions of 18.77R2O3-4.83Y2O3-28.22TiO2-8.75ZrO2-39.43Al2O3 (R = La, Sm, Gd) and elaborated successfully the glassy samples through a containerless solidification process. The as-prepared samples demonstrated the outstanding mechanical and optical properties. The measured hardness, Young's modulus, and indentation fracture toughness of the high-entropy (R = Gd) glass are 12.58 GPa, 177.9 GPa, and 1.52 MPa·m0.5, respectively, in which the hardness and Young's modulus exhibit the highest value among the reported oxide glasses. Structural analysis revealed that the excellent mechanical properties are attributed to the large dissociation energies and the high field strength of Al2O3, TiO2, and ZrO2 and the complex interaction between atoms caused by high entropy.

Experimental Investigation on Mechanism of Latent Heat Reduction of Sodium Acetate Trihydrate Phase Change Materials.

Sodium acetate trihydrate (SAT) phase change material (PCM) has been well known for thermal energy storage due to its high latent heat and resource abundance. However, SAT suffers from severe latent heat reduction after heating and cooling cycles. Although a few of previous researches showed the reduction could be effectively inhibited by using thickeners, the mechanisms of the reduction process and thickeners' inhibition have not been deeply explored till now. In this work, SAT modified by 5 wt.% nucleating agent of disodium hydrogen phosphate dodecahydrate (SAT/5 wt.% DSP) was prepared and 200 thermal cycles were carried out. The differential scanning calorimeter, Rheometer, X-ray diffractometry, and scanning electron microscope were used to investigate the extent of latent heat reduction, viscosity, phase composition and microstructure, respectively, and the infrared thermal imaging method was used to evaluate heat storage capacity. It was found that the latent heat of SAT/5 wt.% DSP dropped dramatically and the relative decrease in latent heat was measured to be 22.44%. The lower layer of SAT/5 wt.% DSP contained 24.1 wt.% CH3COONa, which was quantitatively consistent with the reduction extent. Furthermore, the phase change endothermic time of the lower layer was only 44.1% of that of the upper. SAT/5 wt.% DSP was further modified by 3 wt.% thickener of carboxymethyl cellulose (SAT/5 wt.% DSP/3 wt.% CMC) and endured 200 thermal cycles. The extent of the latent heat reduction of SAT/5 wt.% DSP/3 wt.% CMC was only 9.29%, and phase compositions were more homogeneous. The 3 wt.% CMC increased viscosity by 14 times, which effectively prevented the Stokes sedimentation velocity of CH3COONa in melts and inhibited the final macroscopic phase separation.

Full spectrum core-shell phosphors under ultraviolet excitation.

A YAG: Ce/MgY4Si3O13:Ce-Y2O3:Eu core-shell structure was designed and accomplished via a urea homogeneous precipitation method. The as prepared phosphors can emit photons with a broad range of wavelengths from 340 nm to 700 nm under excitation light of 330 nm. The internal quantum efficiency can reach up to 68%.

Analysis of volumetric response of pituitary adenomas receiving adjuvant CyberKnife stereotactic radiosurgery with the application of an exponential fitting model.

Tumor control rates of pituitary adenomas (PAs) receiving adjuvant CyberKnife stereotactic radiosurgery (CK SRS) are high. However, there is currently no uniform way to estimate the time course of the disease. The aim of this study was to analyze the volumetric responses of PAs after CK SRS and investigate the application of an exponential decay model in calculating an accurate time course and estimation of the eventual outcome.A retrospective review of 34 patients with PAs who received adjuvant CK SRS between 2006 and 2013 was performed. Tumor volume was calculated using the planimetric method. The percent change in tumor volume and tumor volume rate of change were compared at median 4-, 10-, 20-, and 36-month intervals. Tumor responses were classified as: progression for >15% volume increase, regression for ≤15% decrease, and stabilization for ±15% of the baseline volume at the time of last follow-up. For each patient, the volumetric change versus time was fitted with an exponential model.The overall tumor control rate was 94.1% in the 36-month (range 18-87 months) follow-up period (mean volume change of -43.3%). Volume regression (mean decrease of -50.5%) was demonstrated in 27 (79%) patients, tumor stabilization (mean change of -3.7%) in 5 (15%) patients, and tumor progression (mean increase of 28.1%) in 2 (6%) patients (P = 0.001). Tumors that eventually regressed or stabilized had a temporary volume increase of 1.07% and 41.5% at 4 months after CK SRS, respectively (P = 0.017). The tumor volume estimated using the exponential fitting equation demonstrated high positive correlation with the actual volume calculated by magnetic resonance imaging (MRI) as tested by Pearson correlation coefficient (0.9).Transient progression of PAs post-CK SRS was seen in 62.5% of the patients receiving CK SRS, and it was not predictive of eventual volume regression or progression. A three-point exponential model is of potential predictive value according to relative distribution. An exponential decay model can be used to calculate the time course of tumors that are ultimately controlled.

Overexpression of TELO2 decreases survival in human high-grade gliomas.

High-grade gliomas are characterized with poor prognosis. To improve the clinical outcome, biomarker is urgently needed for distinguishing oncotarget in high-grade gliomas. Telomere maintenance 2 (TELO2) regulates S-phase checkpoint in cell cycle, and is involved in DNA repair. However, the role of TELO2 in survival outcome of high-grade gliomas is still not yet clarified. This study aims to investigate the correlation between TELO2 mRNA expression and survival outcome of patients with high-grade gliomas. Based on bioinformatics study, we found that Kaplan-Meier analysis demonstrated shorter survival in patients with higher TELO2 mRNA levels than in those with lower TELO2 expression (median survival, 59 vs. 113 weeks, p=0.0017, by log-rank test, hazard ratio: 0.3505, 95% CI: 01824.-0.6735). TELO2 mRNA expression significantly higher in World Health Organization (WHO) grade IV than in non-tumor control (p=2.85 x 10-9). Moreover, TELO2 level was greater in WHO grade III than in non-tumor controls (p= 0.017) human gliomas. We further validated TELO2 mRNA expression and protein levels by using quantitative RT-PCR, Western blot, and immunohistochemical (IHC) stain of tissue microarray. Consistently, the TELO2 mRNA and protein expression were significantly elevated in human glioma cells in comparison with normal brain control. Additionally, IHC staining showed higher TELO2 immunostain score in high-grade gliomas than in low-grade gliomas, or normal brain control. Taken together, human high-grade gliomas increase TELO2 mRNA expression, and overexpression of TELO2 mRNA expression correlates with shorter survival outcome, supporting that TELO2 is an oncotarget in human gliomas.

Image analysis of open-door laminoplasty for cervical spondylotic myelopathy: comparing the influence of cord morphology and spine alignment.

OBJECTIVES: Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. METHODS: Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. RESULTS: By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome - patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology - the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. CONCLUSIONS: These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty.

DDX3X Biomarker Correlates with Poor Survival in Human Gliomas.

Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked (DDX3X) controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC) staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81) than in non-tumor controls (n = 23, p = 1.13 × 10(-10)). Moreover, DDX3X level was also higher in WHO grade III (n = 19) than in non-tumor controls (p = 2.43 × 10(-5)). Kaplan-Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24) than in those with low DDX3X expression (n = 53) (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893-0.6496). Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas.

Correlation between magnetic resonance imaging grading and pathological grading in meningioma.

OBJECT: This study investigated the specific preoperative MRI features of patients with intracranial meningiomas that correlate with pathological grade and provide appropriate preoperative planning. METHODS: From 2006 to 2012, 120 patients (36 men and 84 women, age range 20-89 years) with newly diagnosed symptomatic intracranial meningiomas undergoing resection were retrospectively analyzed in terms of radiological features of preoperative MRI. There were 90 WHO Grade I and 30 WHO Grade II or III meningiomas. The relationships between MRI features and WHO histopathological grade were analyzed and scored quantitatively. RESULTS: According to the results of multivariate logistic regression analysis, age ≥ 75 years, indistinct tumorbrain interface, positive capsular enhancement, and heterogeneous tumor enhancement were identified factors in the prediction of advanced histopathological grade. The prediction model was quantified as a scoring scale: 2 × (age) + 5 × (tumor-brain interface) + 3 × (capsular enhancement) + 2 × (tumor enhancement). The calculated score correlated positively with the probability of high-grade meningioma. CONCLUSIONS: This scoring approach may be useful for clinicians in determining therapeutic strategy and in surgical planning for patients with intracranial meningiomas.