Ovarian cancer spheroids constitute a metastatic niche for transcoelomic spread that also engenders drug resistance. Spheroid-forming cells express active STAT3 signaling and display stem cell-like ...properties that may contribute to ovarian tumor progression. In this study, we show that STAT3 is hyperactivated in ovarian cancer spheroids and that STAT3 disruption in this setting is sufficient to relieve chemoresistance. In an NSG murine model of human ovarian cancer, STAT3 signaling regulated spheroid formation and self-renewal properties, whereas STAT3 attenuation reduced tumorigenicity. Mechanistic investigations revealed that Wnt signaling was required for STAT3-mediated spheroid formation. Notably, the Wnt antagonist DKK1 was the most strikingly upregulated gene in response to STAT3 attenuation in ovarian cancer cells. STAT3 signaling maintained stemness and interconnected Wnt/β-catenin signaling via the miR-92a/DKK1-regulatory pathways. Targeting STAT3 in combination with paclitaxel synergistically reduced peritoneal seeding and prolonged survival in a murine model of intraperitoneal ovarian cancer. Overall, our findings define a STAT3-miR-92a-DKK1 pathway in the generation of cancer stem-like cells in ovarian tumors, with potential therapeutic applications in blocking their progression.
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Discovering new nonlinear optical (NLO) materials that require an optimization between multiple properties is a time-consuming and high-cost process. To speed up material development, a ...first-principles high-throughput screening pipeline for nonlinear optical materials (FHSP-NLO) that combines density functional theory (DFT) codes, linear and nonlinear optical property calculation codes, and data transformation and extraction codes has been developed for searching promising NLO materials from crystals collected in the Inorganic Crystal Scientific Structure Database (ICSD). The tests for a dozen of well-known NLO crystals covering deep-ultraviolet (DUV), UV, vis–NIR, and middle/far-infrared (M-F-IR) wavelength ranges verify the high-accuracy of FHSP-NLO. Subsequently, nearly 300 noncentrosymmetric borates are tested with FHSP-NLO. The screened deep-ultraviolet (DUV) NLO crystals are fully consistent with previously reported results. Besides, five crystals, whose NLO properties have not been reported, i.e., B2S2O9, Al4B6O15, HP-Na2B4O7, KB(SO3CI)4, and H3BO3-3T, are identified as new promising NLO materials. Two hydrated borates Ca2B5O9·H(OH)2 and Ca(B8O11(OH)4), whose second-harmonic generation (SHG) responses are primarily measured, are screened out and suggested to grow large-size crystals for further evaluation. FHSP-NLO provides a powerful and efficient tool to screen and reduce the total number of experiments necessary for searching NLO materials from reported crystals.
In this study, a series of tetrafluoroborates with non‐π‐conjugated BF4 tetrahedra are investigated systematically by first‐principles calculations. Theoretical studies demonstrate that ...tetrafluoroborates with alkali and/or alkaline‐earth metals are more favorable for deep‐ultraviolet transmission and are comparable to the classical deep‐ultraviolet (deep‐UV) material, MgF2. Furthermore, bandgap decrease with the increasing of ionic radii in alkali and/or alkaline‐earth metals. Introducing highly polarizable cations with d10‐configuration or cations with lone pair electrons into the structure will decrease the bandgaps. The birefringence and second harmonic generation effects are not large enough in tetrafluoroborates because polarizability anisotropy and hyperpolarizability in non‐π‐conjugated BF4 tetrahedra are much smaller than those in π‐conjugated groups. However, the second harmonic generation effect for BF4 tetrahedra has a higher contribution in comparison with that due to birefringence. To effectively synthesize the borate fluorides or fluorooxoborates in the deep‐UV region, raw materials with B−F bonds are preferred.
Tetrafluoroborates containing non‐π‐conjugated BF4 tetrahedra with alkali and/or alkaline‐earth metals are suitable candidates for deep‐ultraviolet optical materials, based on theoretical calculations. These compounds are comparable to the classical deep‐ultraviolet material MgF2.
The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother‐to‐infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, ...multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen–positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30‐32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF‐group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375–386
Owing to wide infrared (IR) transparency ranges, high laser damage thresholds, and being easy to grow in open air, germanates are emerging as promising mid-infrared (mid-IR) nonlinear optical (NLO) ...materials. However, the germanates as NLO materials have not been investigated comprehensively and the crystals with large second harmonic generation (SHG) response have not been identified. Herein, we used the first-principles high-throughput screening pipeline for NLO materials to search for excellent NLO crystals from germanates collected in the inorganic crystal structure database. After two steps of screening, three crystals are picked out from 128 structures based on their predicted energy gaps, birefringences, and SHG coefficients. Subsequently, the three germanates are synthesized and measured. The results show that Pb3Ga2Ge4O14 and Ba2TiGe2O8 exhibit a wide energy gap (>3.1 eV) and a strong phase-matchable SHG intensity that are comparable to the benchmark AgGaS2 (0.8 and 1.2 × AgGaS2, respectively). In addition, the statistical analyses of different categories classified according to their cations show that the d0-transition metal and lone pair cations are more conducive to achieving a larger SHG response and birefringence compared to other cations in germanates. It gives a guideline for exploring new mid-IR NLO materials.
The soft and polar nature of quasi‐2D (PEA)2PbBr4 perovskite, and robust photo‐generated excitons lead exciton‐polaritons and exciton‐polarons as the important phenomena near the band edge for ...application in the lighting aspect. In this work, a convenient methodology is proposed based on the polariton resonant modes in temperature‐dependent (77 K to RT) spectroscopy, and investigate the effect of these quasi‐particles on refractive index dispersion. The large binding energy (≈335 meV) of quasi‐2D excitons is obtained by the reflectance measurements at 77 K. Stable exciton‐polaritons and exciton‐polarons are confirmed by energy dispersions and the observation of self‐trapped exciton‐polaron state, respectively. Furthermore, the large negative thermal‐optic coefficient due to damping effect of exciton‐phonon scattering is observed. The phenomenon is opposite to those observed in conventional semiconductors (e.g., Si, Ge, GaN, AlN, GaAs, AlAs, and ZnO etc.). The observed stable negative thermal‐optic coefficients from 160 K to RT indicate that the quasi‐2D perovskite can be used as a phase compensator for conventional semiconductor materials.
The shrinkage of the energy difference between lower polariton branches (LPs) and upper polariton branches (UPs) proves that oscillator strength decreases when the temperature rises from 77 to 300 K. Therefore, the strong damping effect of exciton‐phonon interactions reduces the oscillator strength when the temperature rises, and further result in the negative thermal‐optic behaviors of quasi‐2D (PEA)2PbBr4 perovskite.
Synthetic lethal screens have the potential to identify new vulnerabilities incurred by specific cancer mutations but have been hindered by lack of agreement between studies. In the case of KRAS, we ...identify that published synthetic lethal screen hits significantly overlap at the pathway rather than gene level. Analysis of pathways encoded as protein networks could identify synthetic lethal candidates that are more reproducible than those previously reported. Lack of overlap likely stems from biological rather than technical limitations as most synthetic lethal phenotypes are strongly modulated by changes in cellular conditions or genetic context, the latter determined using a pairwise genetic interaction map that identifies numerous interactions that suppress synthetic lethal effects. Accounting for pathway, cellular and genetic context nominates a DNA repair dependency in KRAS-mutant cells, mediated by a network containing BRCA1. We provide evidence for why most reported synthetic lethals are not reproducible which is addressable using a multi-faceted testing framework.
Background
The most appropriate procedure for the treatment of super obesity (BMI
>
50 kg/m
2
) is unknown. We aimed to evaluate the safety, long-term (
>
5 years) weight loss, and adverse events ...between three commonly performed procedures, sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB) in super-obese patients.
Methods
Between January 2002 and December 2015, 498 successive patients with super morbid obesity (BMI
>
50), who underwent SG or RYGB or OAGB, were recruited. Surgical outcome, weight loss, resolution of co-morbidities, and late complications were followed and compared between the 3 groups. All data derived from a prospective bariatric database and a retrospective analysis was conducted.
Results
The average patient age was 32.1 ± 10.4 years, with a mean body mass index (BMI) of 56.0 ± 6.7 kg/m
2
. Of them, 190 (38.9%) underwent SG, 62 (12.4%) RYGB, and 246 (49.4%) OAGB. There was no difference in basic characters between the 3 groups except SG had fewer diabetic patients. RYGB group had higher intraoperative blood loss, longer operating time, and hospital stay than the other 2 groups. RYGB had a higher 30-days post-operative major complication rate (4.8%) than SG (0.5%) and OAGB (0.8%). The follow-up rate at 1 and 5 years was 89.4% and 52.0%. At post-operative 5 years, OAGB had a higher total weight loss (40.8%) than SG (35.1%), but not RYGB (37.2%). SG had a lower remission rate in dyslipidemia comparing to OAGB and RYGB, but T2DM remission rate was no different between the groups. The overall revision rate is 5.4% (27/498) of the whole group, and SG had a lower revision rate (2.6%) than RYGB (8.1%) and OAGB (6.9%).
Conclusion
SG is an effective and durable primary bariatric procedure for the treatment of super obesity and metabolic disorders. OAGB had a similar operation risk to SG but resulted in a better weight loss than SG.
Graphical Abstract
Oxonitridosilicates, in which O atoms in SiO
4
are partially substituted by N atoms, are proposed to improve optical anisotropies of silicates as UV NLO materials. The optical properties calculation ...showed that the heteroleptic SiO
x
N
4−
x
(
x
= 1-3) tetrahedra have strong polarizability anisotropy and large hyperpolarizability. Accordingly, nine noncentrosymmetric (NCS) oxonitridosilicate crystals collected in the inorganic crystal structural database (ICSD) are evaluated by using the first principles method. Finally, Si
2
N
2
O and LiSiON are screened out owing to wide band gaps (6.49 and 6.95 eV), large birefringences (0.102 and 0.060 at 1064 nm), and large SHG coefficients (3.3 and 2.2 times that of
d
36
(KDP)). More importantly, the cation selection and structural characteristics that are beneficial for enhancing the band gap and birefringence are identified. This study provides a novel strategy to design and find UV NLO crystals.
Oxonitridosilicates are proposed to improve optical anisotropies of silicates as ultraviolet nonlinear optical materials by using the first principles method.
An active-matrix (AM) driving circuit using a low-temperature poly-silicon thin-film transistor (LTPS TFT) is developed to reduce the power consumption of mini-light-emitting diode (LED) backlit ...liquid-crystal displays (LCDs). By lowering the drain-source voltage (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {DS}} </tex-math></inline-formula>) of the switching TFT on the driving current path, the range of required voltage across the proposed circuit can be reduced, decreasing the power consumption of the mini-LED backlight. The proposed circuit also can compensate for <inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}} </tex-math></inline-formula> variation in the LTPS TFT and the <inline-formula> <tex-math notation="LaTeX">{I} </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">{R} </tex-math></inline-formula> rise of <inline-formula> <tex-math notation="LaTeX">{V}_{\text {SS}} </tex-math></inline-formula> to provide a uniform driving current to flow through the mini-LED. By measuring the <inline-formula> <tex-math notation="LaTeX">{I} </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">{V} </tex-math></inline-formula> curves of a fabricated LTPS TFT, we build a reliable simulation model and compare the proposed circuit to that of the state-of-the-art. Simulated results indicate that the proposed circuit can improve the power consumption by 16.67% and reduce the current error rates below 8% when the <inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}} </tex-math></inline-formula> of TFT varies by ±0.3 V and <inline-formula> <tex-math notation="LaTeX">{V}_{\text {SS}} </tex-math></inline-formula> rises +1 V. Measured results further confirm that the <inline-formula> <tex-math notation="LaTeX">{V}_{\text {DS}} </tex-math></inline-formula> of the switching TFT is reduced by 2.208 V compared to a 6T2C compensating circuit. Therefore, widespread applications of the proposed circuit for AM mini-LED backlit LCDs to produce high-dynamic-range images are foreseeable.
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