Where PI3K/Akt Meets Smads: The Crosstalk Determines Human Embryonic Stem Cell Fate

Coordinated interactions between signaling networks govern the balance of cell fate decisions in human embryonic stem cells. In this issue, Singh et al. (2012) report that PI3K/Akt signaling switches Activin/Smad activity between pro-self-renewal and prodifferentiation by regulating ERK and GSK3β/β-catenin signaling

10 kHz repetition rate picosecond green laser for high-accuracy satellite ranging

Picosecond pulse laser is the main light source for satellite laser ranging. In this paper, a 10 kHz repetition rate picosecond green laser with an average output power of 5.3 W is demonstrated. The laser generates a pulse width of 18.6 ps at a center wavelength of 532.20 nm with a spectral width of .066 nm. The beam quality is well preserved with M2 of 1.1 with the beam divergence measured to be .62 mrad and pointing stability of 7 μrad over 30 min of operation. The laser system was then applied to measure the BeiDou satellite (Compass-I3) and generated a single range accuracy of 3.2 mm, which is the highest reported range accuracy for synchronous orbit satellite laser ranging

FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC

Background/Aims: Forkhead box D1 (FOXD1) has a well-established role in early embryonic development and organogenesis and functions as an oncogene in several cancers. However, the clinical significance and biological roles of FOXD1 in non-small cell lung cancer (NSCLC) remain largely unknown. Methods: A total of 264 primary NSCLC tissue samples were collected. The expression levels of FOXD1 in these samples were examined by immunohistochemical staining. The expression of FOXD1 was knocked down by lentiviral shRNA. The relative expression of FOXD1 was determined by qRT-PCR, Western blotting and immunofluorescence image. The functional roles of FOXD1 in NSCLC were demonstrated cell viability CCK-8 assay, colony formation, cell invasion and migration assays, and cell apoptosis assay in vitro. In vivo mouse xenograft and metastasis models were used to assess tumorigenicity and metastatic ability. The Chi-square test was used to assess the correlation between FOXD1 expression and the clinicopathological characteristics. Survival curves were estimated by Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Results: We determined that higher levels of FOXD1 were present in NSCLC tissues, especially in metastatic NSCLC tissues. FOXD1 was also higher in all NSCLC cells compared with normal human bronchial epithelial cells. A higher expression level of FOXD1 was associated with malignant behavior and poor prognosis in NSCLC patients. Knockdown of FOXD1 significantly inhibited proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo, and it increased the apoptosis rates of NSCLC cells. Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in NSCLC. Multivariate Cox regression analysis indicated that FOXD1 was an independent prognostic factor both for overall survival (OS) and disease-free survival (DFS) in NSCLC patients. Conclusion: Our results indicated that FOXD1 might be involved in the development and progression of NSCLC as an oncogene, and thereby might be a potential therapeutic target for NSCLC patients

A Left Ventricular Mechanical Dyssynchrony-Based Nomogram for Predicting Major Adverse Cardiac Events Risk in Patients With Ischemia and No Obstructive Coronary Artery Disease.

Background The risk stratification of patients with ischemia and no obstructive coronary artery disease (INOCA) remains suboptimal. This study aims to establish a left ventricular mechanical dyssynchrony (LVMD)-based nomogram to improve the present situation. Methods Patients with suspected coronary artery disease (CAD) were retrospectively enrolled and divided into three groups: normal (stenosis 4, summed difference score ≥2), and obstructive CAD (stenosis ≥50%). LVMD was defined by ROC analysis. INOCA group were followed up for the occurrence of major adverse cardiac events (MACEs: cardiovascular death, non-fatal myocardial infarction, revascularization, stroke, heart failure, and hospitalization for unstable angina). Nomogram was established using multivariate Cox regression analysis. Results Among 334 patients (118 [35.3%] INOCA), LVMD parameters were significantly higher in INOCA group versus normal group but they did not differ between obstructive CAD groups. In INOCA group, 27 (22.9%) MACEs occurred during a 26-month median follow-up. Proportion of LVMD was significantly higher with MACEs under both stress (63.0% vs. 22.0%, P < 0.001) and rest (51.9% vs. 20.9%, P = 0.002). Kaplan-Meier analysis revealed significantly higher rate of MACEs (stress log-rank: P = 0.002; rest log-rank: P < 0.001) in LVMD patients. Multivariate Cox regression analysis showed that stress LVMD (HR: 3.82; 95% CI: 1.30-11.20; P = 0.015) was an independent predictor of MACEs. The internal bootstrap resampling approach indicates that the C-index of nomogram was 0.80 (95% CI: 0.71-0.89) and the AUC values for 1 and 3 years of risk prediction were 0.68 (95% CI: 0.46-0.89) and 0.84 (95% CI: 0.72-0.95), respectively. Conclusion LVMD-based nomogram might provide incremental prognostic value and improve the risk stratification in INOCA patients

The prognostic value of CZT SPECT myocardial blood flow (MBF) quantification in patients with ischemia and no obstructive coronary artery disease (INOCA): a pilot study.

BACKGROUND Despite the demonstrated adverse outcome, it is difficult to early identify the risks for patients with ischemia and no obstructive coronary artery disease (INOCA). We aimed to explore the prognostic potential of CZT SPECT in INOCA patients. METHODS The study population consisted of a retrospective cohort of 118 INOCA patients, all of whom underwent CZT SPECT imaging and invasive coronary angiography (ICA). Dynamic data were reconstructed, and MBF was quantified using net retention model. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization for unstable angina. RESULTS During a median follow-up of 15 months (interquartile range (IQR) 11-20), 19 (16.1%) MACEs occurred; both stress myocardial blood flow (sMBF) ([Formula: see text]) and coronary flow reserve (CFR) ([Formula: see text]) were significantly lower in the MACE group. Optimal thresholds of sMBF<3.16 and CFR<2.52 were extracted from the ROC curves, and both impaired sMBF (HR: 15.08; 95% CI 2.95-77.07; [Formula: see text]) and CFR (HR: 6.51; 95% CI 1.43-29.65; [Formula: see text]) were identified as prognostic factors for MACEs. Only sMBF<3.16 (HR: 11.20; 95% CI 2.04-61.41; [Formula: see text]) remained a robust predictor when sMBF and CFR were integrated considered. Compared with CFR, sMBF provides better prognostic model discrimination and reclassification ability (C-index improvement = 0.06, [Formula: see text]; net reclassification improvement (NRI) = 0.19; integrated discrimination improvement (IDI) = 0.10). CONCLUSION The preliminary results demonstrated that quantitative analysis on CZT SPECT provides prognostic value for INOCA patients, which may allow the stratification for early prevention and intervention

Water sorptivity of unsaturated fractured sandstone: fractal modeling and neutron radiography experiment

The spontaneous imbibition of water into the matrix and gas-filled fractures of unsaturated porous media is an important phenomenon in many geotechnical applications. Previous studies have focused on the imbibition behavior of water in the matrix, but few works have considered spontaneous imbibition along fractures. In this work, a new fractal model, considering the water losses from the fracture to the matrix, was established to predict the sorptivity of rough-walled fracture. A fractal model, considering the fractal dimension of tortuosity, was modified to estimate the sorptivity of the matrix. Both of the models have a time exponent α and can be simplified to the classical Lucas–Washburn (L–W) equation with α = 0.50. To verify the proposed models, quantitative data on the imbibition of water in both the matrix and the fracture of unsaturated sandstone were acquired by neutron radiography. The results show that the motion of the wetting front in both the matrix and the fracture does not obey the L–W equation. Both theory and experimental observations indicate that fracture can significantly increase spontaneous imbibition in unsaturated sandstone by capillary action. Compared with the classical L–W equation, the models proposed in this study offers a better description of the dynamic imbibition behaviour of water in unsaturated fractured sandstone and, thus, more reliable predictions of the sorptivity of the matrix and the fracture. Moreover, a new method to estimate the time exponent of rough-walled fracture in sandstone was also provided

Introgression of Powdery Mildew Resistance Gene Pm56 on Rye Chromosome Arm 6RS Into Wheat

Powdery mildew, caused by the fungus Blumeria graminis f. sp. tritici, represents a yield constraint in many parts of the world. Here, the introduction of a resistance gene carried by the cereal rye cv. Qinling chromosome 6R was transferred into wheat in the form of spontaneous balanced translocation induced in plants doubly monosomic for chromosomes 6R and 6A. The translocation, along with other structural variants, was detected using in situ hybridization and genetic markers. The differential disease response of plants harboring various fragments of 6R indicated that a powdery mildew resistance gene(s) was present on both arms of rye chromosome 6R. Based on karyotyping, the short arm gene, designated Pm56, was mapped to the subtelomere region of the arm. The Robertsonian translocation 6AL⋅6RS can be exploited by wheat breeders as a novel resistance resource