•Rent-seeking in bank credit significantly impedes firms’ R&D innovation.•Industrial agglomeration could correct the impeding effect of rent-seeking in bank credit on firm R&D innovation.•The ...moderating role of industrial agglomeration in correcting the negative effect of rent-seeking in bank credit on firm R&D innovation is more prominent for SMEs, non-state firms and firms with more severe financing constraint.•The spatial agglomeration of industries can effectively alleviate the suppression effect of rent-seeking in credit corruption on firm R&D innovation.
Employing World Bank's survey data on the Chinese business environment, we empirically investigate the role of industrial agglomeration in moderating the effect of rent-seeking in bank credit on firm R&D innovation. The results show that rent-seeking in bank credit impedes firm R&D innovation, while industrial agglomeration corrects this impeding effect, which is also robust when considering endogenous problems. Furthermore, the results show that the moderating role of industrial agglomeration in correcting the negative effect of rent-seeking in bank credit on firm R&D innovation is more prominent for SMEs, non-state firms, and firms with more severe financial constraints. These findings suggest that the spatial agglomeration of industries can effectively alleviate the suppression effect of rent-seeking in credit corruption on firm R&D innovation, highlighting ways to promote firm R&D innovation in China's financially repressive environment.
Natural creatures, from fish and cephalopods to snakes and birds, combine neural control, sensory feedback and compliant mechanics to effectively operate across dynamic, uncertain environments. In ...order to facilitate the understanding of the biophysical mechanisms at play and to streamline their potential use in engineering applications, we present here a versatile numerical approach to the simulation of musculoskeletal architectures. It relies on the assembly of heterogenous, active and passive Cosserat rods into dynamic structures that model bones, tendons, ligaments, fibers and muscle connectivity. We demonstrate its utility in a range of problems involving biological and soft robotic scenarios across scales and environments: from the engineering of millimeter-long bio-hybrid robots to the synthesis and reconstruction of complex musculoskeletal systems. The versatility of this methodology offers a framework to aid forward and inverse bioengineering designs as well as fundamental discovery in the functioning of living organisms.
Identification of drug-target interactions is an important process in drug discovery. Although high-throughput screening and other biological assays are becoming available, experimental methods for ...drug-target interaction identification remain to be extremely costly, time-consuming and challenging even nowadays. Therefore, various computational models have been developed to predict potential drug-target associations on a large scale. In this review, databases and web servers involved in drug-target identification and drug discovery are summarized. In addition, we mainly introduced some state-of-the-art computational models for drug-target interactions prediction, including network-based method, machine learning-based method and so on. Specially, for the machine learning-based method, much attention was paid to supervised and semi-supervised models, which have essential difference in the adoption of negative samples. Although significant improvements for drug-target interaction prediction have been obtained by many effective computational models, both network-based and machine learning-based methods have their disadvantages, respectively. Furthermore, we discuss the future directions of the network-based drug discovery and network approach for personalized drug discovery based on personalized medicine, genome sequencing, tumor clone-based network and cancer hallmark-based network. Finally, we discussed the new evaluation validation framework and the formulation of drug-target interactions prediction problem by more realistic regression formulation based on quantitative bioactivity data.
A multistep diffusion-mediated process was developed to control the nucleation density, size, and lateral growth rate of WSe2 domains on c-plane sapphire for the epitaxial growth of large area ...monolayer films by gas source chemical vapor deposition (CVD). The process consists of an initial nucleation step followed by an annealing period in H2Se to promote surface diffusion of tungsten-containing species to form oriented WSe2 islands with uniform size and controlled density. The growth conditions were then adjusted to suppress further nucleation and laterally grow the WSe2 islands to form a fully coalesced monolayer film in less than 1 h. Postgrowth structural characterization demonstrates that the WSe2 monolayers are single crystal and epitaxially oriented with respect to the sapphire and contain antiphase grain boundaries due to coalescence of 0° and 60° oriented WSe2 domains. The process also provides fundamental insights into the two-dimensional (2D) growth mechanism. For example, the evolution of domain size and cluster density with annealing time follows a 2D ripening process, enabling an estimate of the tungsten-species surface diffusivity. The lateral growth rate of domains was found to be relatively independent of substrate temperature over the range of 700–900 °C suggesting a mass transport limited process, however, the domain shape (triangular versus truncated triangular) varied with temperature over this same range due to local variations in the Se/W adatom ratio. The results provide an important step toward atomic level control of the epitaxial growth of WSe2 monolayers in a scalable process that is suitable for large area device fabrication.
Summary Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from ...Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.
A defect-controlled approach for the nucleation and epitaxial growth of WSe2 on hBN is demonstrated. The WSe2 domains exhibit a preferred orientation of over 95%, leading to a reduced density of ...inversion domain boundaries (IDBs) upon coalescence. First-principles calculations and experimental studies as a function of growth conditions and substrate pretreatment confirm that WSe2 nucleation density and orientation are controlled by the hBN surface defect density rather than thermodynamic factors. Detailed transmission electron microscopy analysis provides support for the role of single-atom vacancies on the hBN surface that trap W atoms and break surface symmetry leading to a reduced formation energy for one orientation of WSe2 domains. Through careful control of nucleation and extended lateral growth time, fully coalesced WSe2 monolayer films on hBN were achieved. Low-temperature photoluminescence (PL) measurements and transport measurements of back-gated field-effect transistor devices fabricated on WSe2/hBN films show improved optical and electrical properties compared to films grown on sapphire under similar conditions. Our results reveal an important nucleation mechanism for the epitaxial growth of van der Waals heterostructures and demonstrate hBN as a superior substrate for single-crystal transition-metal dichalcogenide (TMD) films, resulting in a reduced density of IDBs and improved properties. The results motivate further efforts focused on the development of single crystal hBN substrates and epilayers for synthesis of wafer-scale single crystal TMD films.
Spin‐dependent contrasting phenomena at K and K′ valleys in monolayer semiconductors have led to addressable valley degree of freedom, which is the cornerstone for emerging valleytronic applications ...in information storage and processing. Tunable and active modulation of valley dynamics in a monolayer WSe2 is demonstrated at room temperature through controllable chiral Purcell effects in plasmonic chiral metamaterials. The strong spin‐dependent modulation on the spontaneous decay of valley excitons leads to tunable handedness and spectral shift of valley‐polarized emission, which is analyzed and predicted by an advanced theoretical model and further confirmed by experimental measurements. Moreover, large active spectral tuning (≈24 nm) and reversible ON/OFF switching of circular polarization of emission are achieved by the solvent‐controllable thickness of the dielectric spacer in the metamaterials. With the on‐demand and active tunability in valley‐polarized emission, chiral Purcell effects can provide new strategies to harness valley excitons for applications in ultrathin valleytronic devices.
Monolayer semiconductors with spin‐dependent contrasting phenomena at K and K′ valleys feature addressable valley degree of freedom for valleytronic applications. Chiral Purcell effects in plasmonic chiral metamaterials are demonstrated to be able to control the relaxation of targeted valley excitons at a monolayer WSe2 in a versatile way, allowing the actively tunable modulation of valley dynamics at room temperature.
Colorectal cancer (CRC) is one of the most common malignant tumors and the third leading cause of cancer-related deaths in the world. It was reported that sophocarpine could attenuate the progression ...of CRC in mice. However, the mechanisms by which sophocarpine regulate the proliferation and migration in CRC remain unclear. Thus, this study aimed to investigate anti-tumor mechanisms of sophocarpine in CRC cells. CCK-8 assay, wound healing assay and transwell migration were used to detect cell proliferation and migration, respectively. In addition, Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to further detect protein expressions and cytokines in vitro. The results revealed that sophocarpine significantly inhibited proliferation in HCT116 and SW620 cells, respectively. Meanwhile, sophocarpine inhibited CRC cells migration via downregulation of the levels of N-cadherin, matrix metalloproteinase (MMP)-9, phosphorylated extracellular signal-regulated kinase (p-ERK), p-mitogen-activated protein kinase kinase (MEK), vascular endothelial growth factor (VEGF)-A, VEGF-C and VEGF-D. Moreover, overexpression of MEK reversed the anti-migration effects of sophocarpine on CRC cells via upregulation of VEGF-A/C/D. Our findings indicated that sophocarpine could inhibit CRC cells migration via downregulation of MEK/ERK/VEGF pathway. Thus, sophocarpine may act as a potential agent for the treatment of CRC.
Abstract
A single biomarker is not adequate to identify patients with gastric cancer (GC) who have the potential to benefit from anti-PD-1/PD-L1 therapy, presumably owing to the complexity of the ...tumour microenvironment. The predictive value of tumour-infiltrating immune cells (TIICs) has not been definitively established with regard to their density and spatial organisation. Here, multiplex immunohistochemistry is used to quantify in situ biomarkers at sub-cellular resolution in 80 patients with GC. To predict the response to immunotherapy, we establish a multi-dimensional TIIC signature by considering the density of CD4
+
FoxP3
−
PD-L1
+
, CD8
+
PD-1
−
LAG3
−
, and CD68
+
STING
+
cells and the spatial organisation of CD8
+
PD-1
+
LAG3
−
T cells. The TIIC signature enables prediction of the response of patients with GC to anti-PD-1/PD-L1 immunotherapy and patient survival. Our findings demonstrate that a multi-dimensional TIIC signature may be relevant for the selection of patients who could benefit the most from anti-PD-1/PD-L1 immunotherapy.
Neuromuscular actuation of biohybrid motile bots Aydin, Onur; Zhang, Xiaotian; Nuethong, Sittinon ...
Proceedings of the National Academy of Sciences,
10/2019, Letnik:
116, Številka:
40
Journal Article
Recenzirano
Odprti dostop
The integration of muscle cells with soft robotics in recent years has led to the development of biohybrid machines capable of untethered locomotion. A major frontier that currently remains ...unexplored is neuronal actuation and control of such muscle-powered biohybrid machines. As a step toward this goal, we present here a biohybrid swimmer driven by on-board neuromuscular units. The body of the swimmer consists of a free-standing soft scaffold, skeletal muscle tissue, and optogenetic stem cell-derived neural cluster containing motor neurons. Myoblasts embedded in extracellular matrix self-organize into a muscle tissue guided by the geometry of the scaffold, and the resulting muscle tissue is cocultured in situ with a neural cluster. Motor neurons then extend neurites selectively toward the muscle and innervate it, developing functional neuromuscular units. Based on this initial construct, we computationally designed, optimized, and implemented light-sensitive flagellar swimmers actuated by these neuromuscular units. Cyclic muscle contractions, induced by neural stimulation, drive time-irreversible flagellar dynamics, thereby providing thrust for untethered forward locomotion of the swimmer. Overall, this work demonstrates an example of a biohybrid robot implementing neuromuscular actuation and illustrates a path toward the forward design and control of neuron-enabled biohybrid machines.
PDF
