Cellular growth, development, and differentiation are tightly controlled by a conserved biological mechanism： the cell cycle. This cycle is primarily regulated by cyclin-dependent kinase （CDK）-cyclin ...complexes, checkpoint kinases, and CDK inhibitors. Deregulation of the cell cycle is a hallmark of the transformation of normal cells into tumor cells. Given its importance in tumorigenesis, several cell cycle inhibitors have emerged as potential therapeutic drugs for the treatment of cancers-both as singleagent therapy and in combination with traditional cytotoxic or molecular targeting agents. In this review, we discuss the mechanisms underlying cell cycle regulation and present small-molecule anticancer drugs that are under development, including both pan-CDK inhibitors and CDK4/6-selective inhibitors. In addition, we provide an outline of some promising CDK inhibitors currently in preclinical and clinical trials that target cell cycle abnormalities in various cancers.
Feynman's path integral approach is to sum over all possible spatiotemporal paths to reproduce the quantum wave function and the corresponding time evolution, which has enormous potential to reveal ...quantum processes in the classical view. However, the complete characterization of the quantum wave function with infinite paths is a formidable challenge, which greatly limits the application potential, especially in the strong-field physics and attosecond science. Instead of brute-force tracking every path one by one, here we propose a deep-learning-performed strong-field Feynman's formulation with a preclassification scheme that can predict directly the final results only with data of initial conditions, so as to attack unsurmountable tasks by existing strong-field methods and explore new physics. Our results build a bridge between deep learning and strong-field physics through Feynman's path integral, which would boost applications of deep learning to study the ultrafast time-dependent dynamics in strong-field physics and attosecond science and shed new light on the quantum-classical correspondence.
Cellular growth, development, and differentiation are tightly controlled by a conserved biological mechanism: the cell cycle. This cycle is primarily regulated by cyclin-dependent kinase (CDK)-cyclin ...complexes, checkpoint kinases, and CDK inhibitors. Deregulation of the cell cycle is a hallmark of the transformation of normal cells into tumor cells. Given its importance in tumorigenesis, several cell cycle inhibitors have emerged as potential therapeutic drugs for the treatment of cancers-both as single-agent therapy and in combination with traditional cytotoxic or molecular targeting agents. In this review, we discuss the mechanisms underlying cell cycle regulation and present small-molecule anticancer drugs that are under development, including both pan-CDK inhibitors and CDK4/6-selective inhibitors. In addition, we provide an outline of some promising CDK inhibitors currently in preclinical and clinical trials that target cell cycle abnormalities in various cancers.
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•LIPMM was proposed to fabricate a cone-shaped protrusions array with hierarchical structure on the Ti6Al4V surface.•The effect of scan line spacing on micro-nano hierarchical ...structure morphology was studied.•The relationship between surface wettability, micro-nano structure and chemical composition were revealed.•The behavior of droplets colliding with surfaces with different contact angles was investigated by experiments and simulations.•Super-hydrophobic Ti6Al4V surface can be obtained by LIPMM technique.
Titanium alloy Ti6Al4V super-hydrophobic surface plays a key role in enhancing the water repellency and anti-condensation of the fuselage. In this study, laser-induced plasma micromachining (LIPMM) is used for processing an array of cone-shaped protrusions on the surface with a micro-nano hierarchical structure. The relationship between surface wettability, micro-nano structure, and surface chemical composition was studied, meanwhile, the droplet impact behavior was experimented and simulated. The study found that with the aging treatment surface C element distribution and content increased significantly, and the wettability changed from superhydrophilic to hydrophobic. As the scan line spacing (50, 40, 30 μm) decreases, the contact angle increased and the hysteresis contact angle decreased. At 50 times and 30 μm line spacing, the contact angle 151.209°>150°, and the hysteresis contact angle 2.619°<10°. The collision experiments reveal that with the increase of the collision velocity (0.44 m/s to 0.98 m/s), the spreading diameter and the rebound height increases. The comparative results of experiments and simulations of collisions present that as the contact angle increases, the spreading diameter decreases, and the rebound height increases. Therefore, the LIPMM is feasible for the fabrication of a superhydrophobic surface and has a wide range of application prospects such as waterproofing, anti-fouling, and anti-icing.
Metal–organic frameworks (MOFs) have emerged as porous solids of a superior type for the fabrication of membranes. However, it is still challenging to prepare a uniformly dispersed robust MOF hybrid ...membrane. Herein, we propose a simple and powerful strategy, namely, coordination‐driven in situ self‐assembly, for the fabrication of MOF hybrid membranes. On the basis of the coordination interactions between metal ions and ligands and/or the functional groups of the organic polymer, this method was confirmed to be feasible for the production of a stable membrane with greatly improved MOF‐particle dispersion in and compatibility with the polymer, thus providing outstanding separation ability. As an experimental proof of concept, a high‐quality ZIF‐8/PSS membrane was fabricated that showed excellent performance in the nanofiltration and separation of dyes from water.
Mopping up the mess: A hybrid membrane composed of the metal–organic framework (MOF) ZIF‐8 and poly(sodium 4‐styrenesulfonate) was prepared by a coordination‐driven in situ self‐assembly method. The MOF particles were well‐dispersed in the polymer in the resulting stable membrane (see picture), which showed excellent performance in the nanofiltration and separation of dyes from water.
► Graphene oxide and polyelectrolyte complex (GO/PEC) nanohybrid membranes. ► Improvement of mechanical and thermal property with low loading of graphene oxide. ► GO membranes improved pervaporation ...selectivity by 6.88%.
Organic–inorganic nanohybrids are believed to be one of the most promising new membrane materials for separation applications. In this study, a new nanohybrid membrane was prepared by incorporating graphene oxide (GO) into polyelectrolyte complexes (PECs). Poly(ethyleneimine)-modified GO and polyacrylic acid were sequentially assembled onto a hydrolyzed polyacrylonitrile ultrafiltration supporting membrane. The nanohybrid membranes were subsequently immersed in polyvinyl alcohol solutions and cross-linked by glutaraldehyde. The assembly process was systematically investigated by scanning electron microscopy, fourier transform infrared analysis, an electrokinetic analyzer, a nano-indenter and thermogravimetric analyzer. The nanoindentation and thermogravimetric experiments in particular indicated that the GO incorporation greatly improved the Young’s modulus, hardness and thermal stability of the membranes. It was found that the resulting membranes had excellent dye removal capacity. The retention of Congo red could reach 99.5% with the permeance of 8.4kg/m2hMPa. In the case of the separation of monovalent and divalent ions, such membranes show good nanofiltration properties. The retention of Mg2+ and Na+ were 92.6% and 43.2%, respectively. Additionally, it was demonstrated that this GO/PECs nanohybrid membrane is also a good candidate for the pervaporation dehydration of different solvent–water mixtures. The water content could be enriched from 5.0wt.% (in the feed) to 95.4wt.% (in the permeate) with the permeate flux of 268g/m2h in the pervaporation of ethanol/water mixture (50°C).
Asthma is a chronic lung inflammatory disease with high incidence. MicroRNA-192-5p (miR-192-5p) was down-regulated in asthmatics. However, the role of miR-192-5p in asthma is still unclear. In ...current study, in vitro, the overexpression of miR-192-5p, matrix metalloproteinase (MMP)-16 and autophagy related 7 (ATG7) was conducted in airway smooth muscle cells (ASMCs). We found that miR-192-5p suppressed cell proliferation, and decreased MMP-16 and ATG7 expression. MMP-16 and ATG7 promoted cell proliferation, and further alleviated the down-regulation of miR-192-5p on proliferation of ASMCs. in vivo, miR-192-5p was down-regulated in asthma mice, and involved in improvement of asthma mice. MiR-192-5p was demonstrated to alleviate inflammation in asthma mice, including decreasing the level of ovalbumin (OVA)-specific IgE, interleukin (IL)-4, IL-5, IL-13, iNOS and COX-2. Moreover, the attenuation of airway remodeling induced by miR-192-5p in asthma mice were expressed by the reduction of fibroblast growth factor-23 (FGF-23) level, decrease in concentrations of MMP-2 and MMP-9 as well as down-regulation of collagen I deposition. Further, miR-192-5p also caused the suppression of autophagy in asthma mice, exhibiting a decrease in LC3II/I, beclin-1 and ATG7, and an increase in p62. Importantly, MMP-16 and ATG7 were confirmed to be targets of miR-192-5p. Therefore, our results indicate that miRNA-192-5p may attenuate airway remodeling and autophagy in asthma via targeting MMP-16 and ATG7.
In this paper, several existing seismic damage models as well as their characteristics were discussed first of all. And then it was figured out that variational history of incremental dissipated ...hysteretic energy of tentative frame columns under different loading cycle levels; the influence of axial compression ratio, type of stirrups, stirrup ratio, reinforcement ratio, strength grade of concrete and shear span ration on the incremental dissipated hysteretic energy was discussed and analysed. The damage index of tentative frame columns was compared and analysed according to the existing seismic damage models, and the seismic damage models adapt to high-strength concrete columns and ordinary-strength concrete columns were offered. The influence of shear span ration, axial compression ratio and stirrup ratio on the damage was discussed and analysed according to the variational history of the damage index under different loading cycle levels. Lastly through analysing all sorts of seismic damage models comparatively, the seismic damage model of high strength concrete frame columns is put forward, which offers good basement for further damage analysis.
We propose a new exact quantization condition for a class of quantum mechanical systems derived from local toric Calabi-Yau threefolds. Our proposal includes all contributions to the energy spectrum ...which are nonperturbative in the Planck constant, and is much simpler than the available quantization condition in the literature. We check that our proposal is consistent with previous works and implies nontrivial relations among the topological Gopakumar-Vafa invariants of the toric Calabi-Yau geometries. Together with the recent developments, our proposal opens a new avenue in the long investigations at the interface of geometry, topology and quantum mechanics.
A
bstract
We find
n
(
n
− 3)
/
2-dimensional regions of the space of kinematic invariants, where all the solutions to the scattering equations (the core of the CHY formulation of amplitudes) for
n
...massless particles are real. On these regions, the scattering equations are equivalent to the problem of finding stationary points of
n
− 3 mutually repelling particles on a finite real interval with appropriate boundary conditions. This identification directly implies that for each of the (
n
− 3)! possible orderings of the
n
− 3 particles on the interval, there exists one stable stationary point. Furthermore, restricting to four dimensions, we find that the separation of the solutions into
k
∈ {2
,
3
, . . . , n
− 2} sectors naturally matches that of permutations of
n
− 3 labels into those with
k
− 2 descents. This leads to a physical realization of the combinatorial meaning of the Eulerian numbers.
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