The generic mitogen-activated protein kinases (MAPK) signaling pathway is shared by four distinct cascades, including the extracellular signal-related kinases (ERK1/2), Jun amino-terminal kinases ...(JNK1/2/3), p38-MAPK and ERK5. Mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) pathway is reported to be associated with the cell proliferation, differentiation, migration, senescence and apoptosis. The literatures were searched extensively and this review was performed to review the role of MAPK/ERK signaling pathway in cell proliferation, differentiation, migration, senescence and apoptosis.
A simple and efficient protocol to generate amidyl radicals from amine functionalities through a manganese‐mediated atom‐transfer reaction has been developed. This approach employs an earth‐abundant ...and inexpensive manganese complex, Mn2(CO)10, as the catalyst and visible light as the energy input. Using this strategy, site‐selective chlorination of unactivated C(sp3)−H bonds of aliphatic amines and intramolecular/intermolecular chloroaminations of unactivated alkenes were readily realized under mild reaction conditions, thus providing efficient access to a range of synthetically valuable alkyl chlorides, chlorinated pyrrolidines, and vicinal chloroamine derivatives. These practical reactions exhibit a broad substrate scope and tolerate a wide array of functional groups, and complex molecules including various marketed drug derivatives.
Out of the blue: A visible‐light‐driven manganese‐mediated procedure for the generation of amidyl radicals from amines is described. This novel strategy enables site‐selective chlorination of unactivated C(sp3)−H bonds of aliphatic amines and intra/intermolecular chloroaminations of unactivated alkenes. These reactions feature a broad substrate scope, good functional‐group tolerance, and scalability.
Frictional Characteristics of Atomically Thin Sheets Lee, Changgu; Li, Qunyang; Kalb, William ...
Science (American Association for the Advancement of Science),
04/2010, Letnik:
328, Številka:
5974
Journal Article
Recenzirano
Using friction force microscopy, we compared the nanoscale frictional characteristics of atomically thin sheets of graphene, molybdenum disulfide (MoS₂), niobium diselenide, and hexagonal boron ...nitride exfoliated onto a weakly adherent substrate (silicon oxide) to those of their bulk counterparts. Measurements down to single atomic sheets revealed that friction monotonically increased as the number of layers decreased for all four materials. Suspended graphene membranes showed the same trend, but binding the graphene strongly to a mica surface suppressed the trend. Tip-sample adhesion forces were indistinguishable for all thicknesses and substrate arrangements. Both graphene and MoS₂ exhibited atomic lattice stick-slip friction, with the thinnest sheets possessing a sliding-length-dependent increase in static friction. These observations, coupled with finite element modeling, suggest that the trend arises from the thinner sheets' increased susceptibility to out-of-plane elastic deformation. The generality of the results indicates that this may be a universal characteristic of nanoscale friction for atomically thin materials weakly bound to substrates.
To explore the variation in rock acoustic emission (AE) characteristics with strain rate, uniaxial compression tests at different loading rates and impact loading tests were conducted on granite ...using a MTS322 rock mechanical test system and split Hopkinson pressure bar (SHPB) system, respectively. The effect of the strain rate on the AE characteristic parameters, rock fracture properties, and destruction evolution were systematically analyzed. The results demonstrated that with increasing strain rate, the cumulative AE count decreases as a power function, and the variation between the cumulative AE count and strain rate can be fitted log-linearly with a slope of 0.48. The peak frequencies of the AE signals are mostly distributed in the zones of 0–100 kHz, 175–250 kHz, and 400–550 kHz. The signal proportion in the 0–100 kHz zone gradually increases with strain rate, while the signal proportions in the 175–250 kHz and 400–550 kHz zone exhibit decreasing trends. A transition of a sudden increase in the RA-value and decrease in the AF-value occurs when the stress reaches a certain level, and the stress level corresponding to this transition will increase with strain rate. Meanwhile, the RA–AF distribution is mostly concentrated on the abscissa in the low strain rate tests, but gradually concentrates on the longitudinal axis as the strain rate increases. This indicates that tensile cracking becomes the dominant fracture mode with increasing strain rate. The b-value decreases with increasing strain rate in the uniaxial compression tests; however, the b-value in the impact loading tests is higher than that in the uniaxial compression tests. Furthermore, to distinguish the signals generated by stress wave propagation from the signals generated by rock fracturing in the impact loading tests, a four-parameter k-means algorithm is used to conduct a clustering analysis. The results indicate that the signals can be classified into four clusters: tensile fracturing signals (cluster A), mixed stress wave and shear fracture signals (cluster B), mixed stress wave and tensile fracture signals (cluster C), and stress wave signals (cluster D).
This paper mainly discusses a novel conceptual framework: fractional Hopfield neural networks (FHNN). As is commonly known, fractional calculus has been incorporated into artificial neural networks, ...mainly because of its long-term memory and nonlocality. Some researchers have made interesting attempts at fractional neural networks and gained competitive advantages over integer-order neural networks. Therefore, it is naturally makes one ponder how to generalize the first-order Hopfield neural networks to the fractional-order ones, and how to implement FHNN by means of fractional calculus. We propose to introduce a novel mathematical method: fractional calculus to implement FHNN. First, we implement fractor in the form of an analog circuit. Second, we implement FHNN by utilizing fractor and the fractional steepest descent approach, construct its Lyapunov function, and further analyze its attractors. Third, we perform experiments to analyze the stability and convergence of FHNN, and further discuss its applications to the defense against chip cloning attacks for anticounterfeiting. The main contribution of our work is to propose FHNN in the form of an analog circuit by utilizing a fractor and the fractional steepest descent approach, construct its Lyapunov function, prove its Lyapunov stability, analyze its attractors, and apply FHNN to the defense against chip cloning attacks for anticounterfeiting. A significant advantage of FHNN is that its attractors essentially relate to the neuron's fractional order. FHNN possesses the fractional-order-stability and fractional-order-sensitivity characteristics.
Biological systems have evolved over billions of years to develop wetting strategies for advantageous structure–property–performance relations that are crucial for their survival. The discovery of ...these intriguing relationships has inspired tremendous efforts to investigate the micro/nanoscale features of naturally occurring structures with superwettability. Researchers have since developed new methods and techniques to construct artificial materials that mimic natural structures and functionalities. Here, a brief review of natural hierarchical architectures with liquid repellent properties is presented, and the critical underlying mechanism is summarized with an emphasis on the micro/nanoscopic architectures. The state‐of‐the‐art micro/nanofabrication techniques for creating bioinspired hierarchical superwettability structures that are categorized by random and exquisite features are also reviewed, followed by an overview of their emerging applications, with special attention to biomedical‐related fields. The development of fabrication techniques enhances capabilities relative to those of living systems, paving the way toward advanced structural materials with superior functions and unprecedented characteristics for potential applications.
Bioinspired superwettability micro/nanoarchitectures including recently developed omniphobic and lubricant‐infused surfaces are reviewed. New developments in fabrication techniques and emerging potential applications of bioinspired hierarchical structural materials are highlighted.
Cyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore ...(mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI.
CsA@PLGA-PEG-SS31 was prepared by nanoprecipitation. CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles. CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern. The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells. CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species. In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart. Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function. Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats.
CsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area. Thus, CsA@PLGA-PEG-SS31 offered a promising therapeutic method for patients with acute myocardial infarction.
Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in ...a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).
The Gut Microbiota and Alzheimer's Disease Jiang, Chunmei; Li, Guangning; Huang, Pengru ...
Journal of Alzheimer's disease,
01/2017, Letnik:
58, Številka:
1
Journal Article
Recenzirano
The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also ...central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.
Grain boundaries in lead halide perovskite films lead to increased recombination losses and decreased device stability under illumination due to defect‐mediated ion migration. The effect of a ...conjugated polymer additive, poly(bithiophene imide) (PBTI), is investigated in the antisolvent treatment step in the perovskite film deposition by comprehensive characterization of perovskite film properties and the performance of inverted planar perovskite solar cells (PSCs). PBTI is found to be incorporated within grain boundaries, which results in an improvement in perovskite film crystallinity and reduced defects. The successful defect passivation by PBTI yields reduces recombination losses and consequently increases power conversion efficiency (PCE). In addition, it gives rise to improved photoluminescence stability and improved PSC stability under illumination which can be attributed to reduced ion migration. The optimal devices exhibit a PCE of 20.67% compared to 18.89% of control devices without PBTI, while they retain over 70% of the initial efficiency after 600 h under 1 sun illumination compared to 56% for the control devices.
A semiconducting conjugated polymer, poly(bithiophene imide), is successfully introduced to perovskite grain boundaries along with augmented grain sizes. This results in effective defect passivation and hence reduced recombination losses and increased efficiency, as well as reduced ion migration and improved stability.
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