A Small Molecule Compound Targeting STAT3 DNA-Binding Domain Inhibits Cancer Cell Proliferation, Migration, and Invasion

Signal transducer and activator of transcription 3 (STAT3) plays important roles in multiple aspects of cancer aggressiveness including migration, invasion, survival, self-renewal, angiogenesis, and tumor cell immune evasion by regulating the expression of multiple downstream target genes. STAT3 is constitutively activated in many malignant tumors and its activation is associated with high histological grade and advanced cancer stages. Thus, inhibiting STAT3 promises an attracting strategy for treatment of advanced and metastatic cancers. Herein, we identified a STAT3 inhibitor, inS3-54, by targeting the DNA-binding domain of STAT3 using an improved virtual screening strategy. InS3-54 preferentially suppresses proliferation of cancer over non-cancer cells and inhibits migration and invasion of malignant cells. Biochemical analyses show that inS3-54 selectively inhibits STAT3 binding to DNA without affecting the activation and dimerization of STAT3. Furthermore, inS3-54 inhibits expression of STAT3 downstream target genes and STAT3 binding to chromatin in situ. Thus, inS3-54 represents a novel probe for development of specific inhibitors targeting the DNA-binding domain of STAT3 and a potential therapeutic for cancer treatments

Controlled Synthesis of Organic/Inorganic van der Waals Solid for Tunable Light-matter Interactions

Van der Waals (vdW) solids, as a new type of artificial materials that consist of alternating layers bonded by weak interactions, have shed light on fascinating optoelectronic device concepts. As a result, a large variety of vdW devices have been engineered via layer-by-layer stacking of two-dimensional materials, although shadowed by the difficulties of fabrication. Alternatively, direct growth of vdW solids has proven as a scalable and swift way, highlighted by the successful synthesis of graphene/h-BN and transition metal dichalcogenides (TMDs) vertical heterostructures from controlled vapor deposition. Here, we realize high-quality organic and inorganic vdW solids, using methylammonium lead halide (CH3NH3PbI3) as the organic part (organic perovskite) and 2D inorganic monolayers as counterparts. By stacking on various 2D monolayers, the vdW solids behave dramatically different in light emission. Our studies demonstrate that h-BN monolayer is a great complement to organic perovskite for preserving its original optical properties. As a result, organic/h-BN vdW solid arrays are patterned for red light emitting. This work paves the way for designing unprecedented vdW solids with great potential for a wide spectrum of applications in optoelectronics

Therapeutic effects of neuregulin-1 in diabetic cardiomyopathy rats

BACKGROUND: Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. The effective treatment strategy for DCM has not been developed. METHODS: Rats were divided into 3 groups with different treatment. The control group was only injected with citrate buffer (n = 8). The diabetes group and diabetes treated group were injected with streptozotocin to induce diabetes. After success of diabetes induction, the rats with diabetes were treated with (diabetes treated group, n = 8) or without (diabetes group, n = 8) recombinant human Neuregulin-1 (rhNRG-1). All studies were carried out 16 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate the cardiac function. Apoptotic cells were determined by TUNEL staining. Left ventricular (LV) sections were stained with Masson to investigate myocardial collagen contents. Related gene expressions were analyzed by quantitative real-time PCR (qRT-PCR). RESULTS: Diabetes impaired cardiac function manifested by reduced LV systolic pressure (LVSP), maximum rate of LV pressure rise and fall (+dp/dt max and -dp/dt max) and increased LV end-diastolic pressure (LVEDP). The rhNRG-1 treatment could significantly alleviate these symptoms and improve heart function. More TUNEL staining positive cells were observed in the diabetic group than that in the control group, and the rhNRG-1 treatment decreased apoptotic cells number. Furthermore, qRT-PCR assay demonstrated that rhNRG-1 treatment could decrease the expression of bax and caspase-3 and increase that of bcl-2. Collagen volume fraction was higher in the diabetic group than in the control group. Fibrotic and fibrotic related mRNA (type I and type III collagen) levels in the myocardium were significantly reduced by administration of rhNRG-1. CONCLUSION: rhNRG-1 could significantly improve the heart function and reverse the cardiac remodeling of DCM rats with chronic heart failure. These results support the clinical possibility of applying rhNRG-1 as an optional therapeutic strategy for DCM treatment in the future

DNetDB: The human disease network database based on dysfunctional regulation mechanism

Additional analysis and concepts explanation. This file contains 1) comparison of DNetDB and the results of differential expression analysis (DEA-) based method ; 2) comparison of DNetDB and traditional disease classification; 3) negative disease relationships and 4) DCp and DCe. (DOCX 6926 kb

Optimal entanglement generation in optomechanical systems via Krotov control of covariance matrix dynamics

We investigated the optimal control of a continuous variable system, focusing on entanglement generation in an optomechanical system without utilizing Fock basis cutoffs. Using the Krotov algorithm to optimize the dynamics of the covariance matrix, we illustrated how to design a control objective function to manipulate the dynamics of the system to generate a desirable target state. We showed that entanglement between the macroscopic mechanical mirror and the quantum optical cavity can be reliably generated through imposing the control on the detuning of the external laser field. It has be shown that the control may be still achieved when imposing spectral constraints on the external field to restrict it to low-frequency components. In addition, we systematically studies the effects of quantum control on non-Markovian open system dynamics. We observed that memory effects can play a beneficial role in mitigating the detrimental impact of environmental noises. Specifically, the entanglement generated shows reduced decay in the presence of these memory effects.Comment: 10 pages, 5 figure

A Search for Double-peaked narrow emission line Galaxies and AGNs in the LAMOST DR1

LAMOST has released more than two million spectra, which provide the opportunity to search for double-peaked narrow emission line (NEL) galaxies and AGNs. The double-peaked narrow-line profiles can be well modeled by two velocity components, respectively blueshifted and redshifted with respect to the systemic recession velocity. This paper presents 20 double-peaked NEL galaxies and AGNs found from LAMOST DR1 using a search method based on multi-gaussian fit of the narrow emission lines. Among them, 10 have already been published by other authors, either listed as genuine double-peaked NEL objects or as asymmetric NEL objects, the remaining 10 being first discoveries. We discuss some possible origins for double-peaked narrow-line features, as interaction between jet and narrow line regions, interaction with companion galaxies and black hole binaries. Spatially resolved optical imaging and/or follow-up observations in other spectral bands are needed to further discuss the physical mechanisms at work.Comment: 17 pages, 5figures, 4 tables, accepted by RA

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material

Inner fission barriers of uranium isotopes in the deformed relativistic Hartree-Bogoliubov theory in continuum

The inner fission barriers of the even-even uranium isotopes from the proton to the neutron drip line are studied with the deformed relativistic Hartree-Bogoliubov theory in continuum. A periodic evolution for the ground state shapes is shown with the neutron number, i.e., spherical shapes at shell closures $N=$126, 184, 258, and prolate dominated shapes between them. In analogy to the shape evolution, the inner fission barriers also exhibit a periodic behavior: peaks at the shell closures and valleys in the mid-shells. The triaxial effect to the inner fission barrier is evaluated using the triaxial relativistic mean field calculations plus a simple BCS method for pairing. With the triaxial correction included, good consistency in the inner barrier heights is found with the available empirical data. Besides, the evolution from the proton to the neutron drip line is in accord with the results by the multi-dimensionally constrained relativistic mean field theory. A flat valley in the fission barrier height is predicted around the neutron-rich nucleus $^{318}$U which may play a role of fission recycling in the astrophysical $r$-process nucleosynthesis.Comment: 7 pages, 6 figure

Glycosylation of the Sodium Channel β4 Subunit is Developmentally Regulated and Involves in Neuritic Degeneration

Aberrant protein glycosylation plays major roles in neurodegenerative diseases, including Parkinson's disease (PD). Glycoproteomics showed that the glycosylation of sodium channel β4 was significantly increased in human brain tissue. β4-specific antibodies reacted in immunoblot assays with the 35- and 38-kDa bands from the membrane fractions isolated from neonatal PD transgenic mice but only with the 35-kDa band of the neonatal wild-type mice. The size of the 38-kDa immunoreactive protein is in close agreement with previously reported, suggesting heavy glycosylation of this protein in adult wild-type and neonatal PD transgenic brain tissues. However, the neonatal wild-type mice membrane fractions only contained the 35-kDa immunoreactive protein, and the additional 38-kDa band was not shown until postnatal day 7. Enzymatic deglycosylation of the membrane preparations only converted the 38-kDa band into a faster migrating protein, which was consistent with heavy glycosylation of this protein. The glycosylated state of β4 was developmentally regulated and was altered in disease state. Neurite outgrowth assay demonstrated that overexpression of deglycosylated mutant β4-MUT accelerated neurite extension and increased the number of filopodia-like protrusions, when compared with β4-WT and the vector. These results suggest that extensive glycosylation of β4 subunit play roles in morphological changes, and the altered glycosylation may be involved in the pathogenesis of PD