A series of undrained cyclic triaxial tests were carried out to study the nonplastic fines on the cyclic behaviour of saturated sand-fines mixtures. The influences of the fines content (FC), global ...void ratio (e), and relative density (Dr) were considered. The results show that the cyclic resistance ratio (CRR) of the mixtures firstly decreases and then increases, finally stabilizing with increasing FC when the samples are prepared at a constant Dr. The CRR reaches its minimum when the FC is 20%. However, the CRR decreases and then increases with increasing FC when the samples are prepared at a constant e. The CRR reaches its minimum when the FC is at 30%. The CRR of the mixtures increases with increasing Dr when the FC is given. A single Dr or e cannot describe the dense state of the mixture effectively. A new index, Dr/e, is proposed in this study to describe the dense state of the mixtures. A semiempirical model is proposed to evaluate the CRR of the mixtures using the parameters of Dr/e and FC of the mixture based on the back analysis method. The applicability of the model is verified by the test data from this study and other scholars. In addition, the parameters of Dr/e and FC of the mixture can be obtained from basic geotechnical tests, which is convenient for the application of the model.
Metastasis is a multistep process that accounts for the majority of cancer-related death. By the end of metastasize dissemination, circulating tumor cells (CTC) need to extravasate the blood vessels ...at metastatic sites to form new colonization. Although cancer cell extravasation is a crucial step in cancer metastasis, it has not been successfully targeted by current anti-metastasis strategies due to the lack of a thorough understanding of the molecular mechanisms that regulate this process. This review focuses on recent progress in cancer extravasation visualization techniques, including the development of both
in vitro
and
in vivo
cancer extravasation models, that shed light on the underlying mechanisms. Specifically, multiple cancer extravasation stages, such as the adhesion to the endothelium and transendothelial migration, are successfully probed using these technologies. Moreover, the roles of different cell adhesive molecules, chemokines, and growth factors, as well as the mechanical factors in these stages are well illustrated. Deeper understandings of cancer extravasation mechanisms offer us new opportunities to escalate the discovery of anti-extravasation drugs and therapies and improve the prognosis of cancer patients.
Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the ...pericardial cavity as a natural "mold" for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.
With the rapidly growing demand for low‐cost and safe energy storage, the advanced battery concepts have triggered strong interests beyond the state‐of‐the‐art Li‐ion batteries (LIBs). Herein, a ...novel hybrid Li/Na‐ion full battery (HLNIB) composed of the high‐energy and lithium‐free Na3V2(PO4)2O2F (NVPOF) cathode and commercial graphite anode mesophase carbon micro beads is for the first time designed. The assembled HLNIBs exhibit two high working voltage at about 4.05 and 3.69 V with a specific capacity of 112.7 mA h g−1. Its energy density can reach up to 328 W h kg−1 calculated from the total mass of both cathode and anode materials. Moreover, the HLNIBs show outstanding high‐rate capability, long‐term cycle life, and excellent low‐temperature performance. In addition, the reaction kinetics and Li/Na‐insertion/extraction mechanism into/out NVPOF is preliminarily investigated by the galvanostatic intermittent titration technique and ex situ X‐ray diffraction. This work provides a new and profound direction to develop advanced hybrid batteries.
A novel Li/Na‐ion hybrid battery with high working voltage and superior electrochemical and low‐temperature properties is designed and assembled by using lithium‐free Na3V2(PO4)2O2F (NVPOF) and commercial graphite as cathode and anode, respectively. The electrode kinetics and Li/Na‐insertion/extraction processes into/out the NVPOF cathode are preliminarily studied by the galvanostatic intermittent titration technique and ex situ X‐ray diffraction.
Single‐crystalline Ni‐rich cathode (SC‐NCM) has attracted increasing interest owing to its greater capacity retention in advanced solid‐state lithium batteries (SSLBs), while suffers from severe ...interfacial instability during cycling. Here, via atomic layer deposition, Li3PO4 is introduced to coat SC‐NCM (L‐NCM), to suppress undesired side reaction and enhance interfacial stability. The dynamic degradation and surface regulation of SC‐NCM are investigated inside a working SSLB by in situ atomic force microscopy (AFM). We directly observe the uneven cathode electrolyte interphase (CEI) and surface defects on pristine SC‐NCM particle. Remarkably, the formed amorphous LiF‐rich CEI on L‐NCM maintains its initial structure upon cycling, and thus endows the battery with improved cycling stability and excellent rate capability. Such on‐site tracking provides deep insights into surface mechanism and structure–reactivity correlation of SC‐NCM, and thus benefits the optimizations of SSLBs.
Insights into the surface mechanism on the single‐crystalline LiNi0.5Co0.2Mn0.3O2 (SC‐NCM) cathode are disclosed by in situ atomic force microscopy in solid‐state batteries. Via atomic layer deposition, the Li3PO4 is introduced to coat SC‐NCM, leading to the uniform formation of LiF‐rich cathode electrolyte interphase and suppression of undesired side reaction, which endows batteries with enhanced interfacial stability, durability and dynamics.
Injection molding has been widely used in the mass production of high-precision products. The finished products obtained through injection molding must have a high quality. Machine parameters do not ...accurately reflect the molding conditions of the polymer melt; thus, the use of machine parameters leads to erroneous quality judgments. Moreover, the cost of mass inspections of finished products has led to strict restrictions on comprehensive quality testing. Therefore, an automatic quality inspection that provides effective and accurate quality judgment for each injection-molded part is required. This study proposes a multilayer perceptron (MLP) neural network model combined with quality indices for performing fast and automatic prediction of the geometry of finished products. The pressure curves detected by the in-mold pressure sensor, which reflect the flow state of the melt, changes in various indicators and molding quality, were considered in this study. Furthermore, the quality indices extracted from pressure curves with a strong correlation with the part quality were input into the MLP model for learning and prediction. The results indicate that the training and testing of the first-stage holding pressure index, pressure integral index, residual pressure drop index and peak pressure index with respect to the geometric widths were accurate (accuracy rate exceeded 92%), which demonstrates the feasibility of the proposed method.
Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) ...derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.
The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.
Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.
The estimated spending on online advertising worldwide will reach $520 billion during 2023, almost double compared with that in 2019. Due to the conjunction of huge expenditure and latent ...inefficiencies, competitive advertising has always been occupying a front-and-center place in marketing, among which research modeled as bilinear differential game is one of the most important. However, by the intrinsic difficulties of mathematics, there is no extant research to augment the analysis with Markov jump process, which is of particular significance to abrupt product-harm crisis or promotion interactions. Motivated by this requirement, iterative algorithm with convergence proof is developed to approximate bilinearity. Kalman filter and nonlinear separation theorem, which enable noise-contaminated sales data for analysis in the partial observation, are also introduce to hone in more actionable and focused in real business. The Simulink modeling in this paper provides a straightforward tool for rapid prototyping of these complex, time-varying, multilayer systems. The simulation model proposed allows automatically exploring competitions and finding the most efficient strategies. Moreover, six application examples, resulting from the permutations of four encounters with different time durations and abrupt impacts, have discovered eight implications. They not only complement the existing work on crisis, but also generalize to promotion, which imply that managers should anticipate the sales bump and optimally increase ad spending ex ante. Most importantly, they have revealed a number of new legal, advertising, competition and partly counterintuitive insights for those struggling to develop successful advertising strategies.
•Bilinear differential game with Markov jump for competitive advertising strategy.•Better interpretation of promotion interactions and product-crisis management.•Analysis system including sales lost due to forgetting and customer switch.•An approximation algorithm for solution with convergence proof.•An iterative simulator is built-in for an automatic solution with high efficiency.
The long‐term outcome of gastric cancer (GC) patients remains unsatisfactory despite some recent improvements. Leukemia inhibitory factor (LIF) is a prognostic biomarker for some solid tumors, ...however its role in GC remains unknown. In this study, we demonstrated that LIF and LIF receptor (LIFR) are overexpressed in GC tissues and established that a correlation exists between them. LIF and LIFR expression are associated with tumor differentiation, lymphovascular invasion, tumor stage, lymph node metastasis, and pTNM stage, indicating that they may be useful prognostic factors. LIF promoted GC cell proliferation, colony formation, invasion, migration, and tumor growth; it also promoted cell cycle progression and inhibited apoptosis; and knocking out the LIFR gene reversed the effects of LIF. LIF inhibited the activity of the Hippo pathway, resulting in reduced phosphorylation of YAP, increased YAP nuclear translocation, and increased cell proliferation. Finally, silencing YAP mRNA expression suppressed cell proliferation. Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR–Hippo–YAP signaling. LIF may therefore be a useful biomarker for GC.
Our results establish a new LIF–LIFR–Hippo–YAP pathway that promotes gastric cancer (GC) proliferation, progression, migration, and invasion. Leukemia inhibitory factor (LIF) plays a crucial role in GC tumorigenesis and the development of an effective LIF or YAP antibody may represent a novel strategy to treat GC.
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