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

Tuning Thermal Conductivity of Hybrid Perovskites through Halide Alloying

Tuning the thermal transport properties of hybrid halide perovskites is critical for their applications in optoelectronics, thermoelectrics, and photovoltaics. Here, we demonstrate an effective strategy to modulate the thermal transport property of hybrid perovskites by halide alloying. A highly tunable thermal conductivity of mixed-halide hybrid perovskites is achieved due to halide-alloying and structural distortion. Our experimental measurements show that the room temperature thermal conductivity of MAPb(BrxI1-x)3 (x = 0-1) can be largely modulated from 0.27 W/mK (x = 0.5) to 0.47 W/mK (x = 1). Molecular dynamics simulations further demonstrate that the thermal conductivity reduction of hybrid halide perovskites results from the suppression of the mean free paths of the low-frequency acoustic and optical phonons. It is found that halide alloying and the induced structural distortion can largely increase the scatterings of optical and acoustic phonons, respectively. The confined diffusion of MA+ cations in the octahedra cage is found to act as an additional thermal transport channel in hybrid perovskites and can contribute around 10-20% of the total thermal conductivity. Our findings provide a strategy for tailoring the thermal transport in hybrid halide perovskites which may largely benefit their related applications

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

Practice and understanding of deep coalbed methane massive hydraulic fracturing in Shenfu Block, Ordos Basin

The proven geological reserves of the Shenfu deep coalbed methane (CBM) field on the eastern margin of the Ordos Basin exceed 100 billion cubic meters. It is of great significance to realizing the efficient development of deep CBM in this region to ensure the national energy supply. However, the complexity of the geological environment which includes high stress, medium-high temperatures, low permeability, strong heterogeneity, and wide developed cleats and natural fractures, makes it challenging for the existed shallow and medium CBM fracturing techniques to be fully applicable to deep CBM resources. As a result, the stimulation scale and parameters for deep coalbed fracturing are still in the trial-and-error stage. In order to explore the stimulation techniques which are compatible with the geological conditions of deep coalbeds, the Shenfu block in the Ordos Basin was taken as the geological background and the large-scale hydraulic fracturing of deep coal seams was conducted as an engineering practice. The authors designed the idea of “Push the limit to the beyond + balanced propagation + effective support”, and proposed the massive hydraulic fracturing techniques based on “multi-stage multi-clusters with moderate-dense cutting + perforation with equal apertures, deep penetration and limited flow + integrated variable viscosity (rock breaking by higher viscous slick water + complex fracture network generating by lower viscous slick water) + high pumping rate with high proppant concentration + pre-acid treatment to reduce the breakdown pressure + graded proppants with multiple sizes to support fractures”. Then, the authors put forward an integrated “Geology-Engineering-AI” workflow to perform post-frac analysis, through double matching and correcting the fracturing pumping pressure and production rate automatically, accurately characterized the stimulated reservoir volume (SRV) and drained rock volume (DRV), and predicted the estimated ultimate recovery (EUR) under different fracturing scales and well types. Finally, by statistically analyzing the gas production characteristics of multiple wells in the Shenfu block and utilizing the random forest method, the primary controlling factors affecting the production capacity of deep CBM were quantitatively analyzed. The results demonstrate that after reservoir stimulation, directional wells can achieve a maximum daily gas production rate exceeding 10 000 m3/d, while horizontal wells can achieve a maximum daily gas production rate exceeding 20 000 m3/d. It indicates that the deep coal beds have good fracturing properties and great development potential. The primary impact factors for peak gas production rate are gas content, coalbed thickness and proppant concentration, while the major impact factors for cumulative gas production include gas content, proppant concentration, and total volume of proppants

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

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

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