Activation of Rac1-PI3K/Akt is required for epidermal growth factorinduced PAK1 activation and cell migration in MDA-MB-231 breast cancer cells

Epidermal growth factor （EGF） may increase cell motility, an event implicated in cancer cell invasion and metastasis. However, the underlying mechanisms for EGF-induced cell motility remain elusive. In this study, we found that EGF treatment could activate Ras-related C3 botulinum toxin substrate 1 （Racl）, PI3K/Akt and p21- actived kinase （PAK1） along with cell migration. Ectopic expression of PAK1 K299R, a dominant negative PAK1 mutant, could largely abolish EGF-induced cell migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably inhibited both EGF-induced PAK1 activation and cell migration. Furthermore, expression of dominant-negative Racl （T17N） could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration. Interestingly, EGF could induce a significant production of ROS, and N-acetyl-L-cysteine, a scavenger of ROS which abolished the EGF-induced ROS generation, cell migration, as well as activation of PI3K/Akt and PAK, but not Racl. Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Racl, generation of ROS and subsequent activation of PI3K/Akt and PAK1.

Throughput Analysis of Dynamic Spectrum Anti-Jamming Multiple-Access in HF Communication Systems

A multiple-access networking scheme based on the new dynamic spectrum anti-jamming system is proposed in this paper. The network consists of a center node and multiple user nodes. The center node detects spectrum holes in the operation band periodically according to the user performance target. Detected spectrum holes are allocated to users who request communication. Throughput of this networking scheme is analyzed over a high-frequency(HF) interference channel. The effect of error correction coding and spectrum hole information transmission error is discussed. Throughput of this scheme and conventional frequency-hopping multiple-access(FHMA) scheme are compared. Results show that user performance increase leads to throughput decrease, which can be offset by error correction coding. If spectrum hole information transmission is in error, the throughput is not affected much as long as the bit error rate is below 10-2. Furthermore, throughput of this scheme is obviously superior to the throughput of FHMA scheme.

Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade

Background:Immune checkpoint blockade(ICB)has revolutionized the treatment of various cancer types.Despite significant preclinical advancements in understanding mechanisms,identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging.Recent evidence,both preclinical and clinical,underscores the pivotal role of the extracellular matrix(ECM)in modulating immune cell infiltration and behaviors.This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy.Methods:We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy.This analysis led to the identification of three distinct immuno-collagenic subtypes predictive of ICB responses.We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas(TCGA)dataset and 1,084 inhouse samples.Additionally,novel therapeutic targets were identified based on these established immuno-collagenic subtypes.Results:Our categorization divided tumors into three subtypes:“soft&hot”(low collagen activity and high immune infiltration),“armored&cold”(high collagen activity and low immune infiltration),and“quiescent”(low collagen activity and immune infiltration).Notably,“soft&hot”tumors exhibited the most robust response to ICB therapy across various cancer types.Mechanistically,inhibiting collagen augmented the response to ICB in preclinical models.Furthermore,these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types.Additionally,an unbiased approach identified B7 homolog 3(B7-H3),an available drug target,as strongly expressed in“armored&cold”tumors,relating with poor prognosis.Conclusion:This study introduces histopathology-based universal immunocollagenic subtypes capable of predicting ICB responses across diverse cancer types.These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

A General Simulation Method for Complex Deformation of Irregular-Shaped Origami Configurations

Most existing treatments for origami-folding simulations have focused on regular-shaped configurations.This article aims to introduce a general strategy for simulating and analyzing the deformation process of irregular shapes by means of computational capabilities nowadays.To better simulate origami deformation with folding orders,the concept of plane follow-up is introduced to achieve automated computer simulation of complex folding patterns,thereby avoiding intersection and penetration between planes.Based on the evaluation criteria such as the lowest storage energy with tightening and the fastest pace from tightening to unfolding,the optimal crease distribution patterns for four irregular(‘N’-,‘T’-,‘O’-,and‘P’-shaped)origami configurations are then presented under five candidates.When the dimensions of the origami are fixed,it is discovered that simpler folding patterns lead to faster deformation of the origami configuration.When the folding complexity is fixed,higher strain energy results in more rapid origami expansion.

Ultrashort-time liquid phase sintering of high-performance fine-grain tungsten heavy alloys by laser additive manufacturing

Liquid phase sintering(LPS)is a proven technique for preparing large-size tungsten heavy alloys(WHAs).However,for densification,this processing requires that the matrix of WHAs keeps melting for a long time,which simultaneously causes W grain coarsening that degenerates the performance.This work develops a novel ultrashort-time LPS method to form bulk high-performance fine-grain WHAs based on the principle of laser additive manufacturing(LAM).During LAM,the high-entropy alloy matrix(Al_(0.5)Cr_(0.9)FeNi_(2.5)V_(0.2))and W powders were fed simultaneously but only the matrix was melted by laser and most W particles remained solid,and the melted matrix rapidly solidified with laser moving away,producing an ultrashort-time LPS processing in the melt pool,i.e.,laser ultrashort-time liquid phase sintering(LULPS).The extreme short dwell time in liquid(-1/10,000 of conventional LPS)can effectively suppress W grain growth,obtaining a small size of 1/3 of the size in LPS WHAs.Meanwhile,strong convection in the melt pool of LULPS enables a nearly full densification in such a short sintering time.Compared with LPS WHAs,the LULPS fine-grain WHAs present a 42%higher yield strength,as well as an enhanced susceptibility to adiabatic shear banding(ASB)that is important for strong armor-piercing capability,indicating that LULPS can be a promising pathway for forming high-performance WHAs that surpass those prepared by conventional LPS.

Classification of inelastic deformation and material-intrinsic indices about mechanical performance of general solid matter

The present article is aimed to detect material-intrinsic indices that can be used to supervise the mechanical performance of general solid matter.The novelty carried in this article can be summarised as follows.Firstly,an inelastic deformation state of almost any solid matter can be treated as the combination of two fundamental modes due to different microscopic causation:Mode I inelastic distortion due to the movement of sliding types of defects and Mode II inelastic dilation due to the evolution of voids/bubbles.Secondly,each inelastic deformation mode is characterised by a single principal inelastic deformation descriptor(PIDD):Mode I by a newly introduced quantity of maximum distortional angle changeαand Mode II by the logarithm of dilating magnificationω.In particular,the concept of maximum distortional angle change gives rise to a geometrically intuitive yield criterion ofα>α_(c),which in situations of small deformation,is shown to asymptote von Mise's,and to become Tresca's in cases of plane stress.Thirdly,the deformation process of a solid matter under monotonic and ambient loads is formulated by means of trajectories of thermodynamic equilibria with respect to the PIDD pair.Then a pair of physical quantities which measure the stresses needed to change the local PIDD state are singled out.Being termed as inelastic deformation resistances(IDRs),these two quantities are shown to depend only on the onsite atomic configurations.It is also shown that key descriptive properties about the mechanical behaviours of materials,such as ductility,are encoded in IDRs as functions of PIDDs.Hence the IDR pair may serve as material performance indices that may be more intrinsic than conventional stress-strain relationships.