Challenges of EGFR-TKIs in NSCLC and the potential role of herbs and active compounds: From mechanism to clinical practice

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used in the treatment of lung cancer, especially in the first-line treatment of advanced NSCLC, and EGFR-TKIs monotherapy has achieved better efficacy and tolerability compared with standard chemotherapy. However, acquired resistance to EGFR-TKIs and associated adverse events pose a significant obstacle to targeted lung cancer therapy. Therefore, there is an urgent need to seek effective interventions to overcome these limitations. Natural medicines have shown potential therapeutic advantages in reversing acquired resistance to EGFR-TKIs and reducing adverse events, bringing new options and directions for EGFR-TKIs combination therapy. In this paper, we systematically demonstrated the resistance mechanism of EGFR-TKIs, the clinical strategy of each generation of EGFR-TKIs in the synergistic treatment of NSCLC, the treatment-related adverse events of EGFR-TKIs, and the potential role of traditional Chinese medicine in overcoming the resistance and adverse reactions of EGFR-TKIs. Herbs and active compounds have the potential to act synergistically through multiple pathways and multiple mechanisms of overall regulation, combined with targeted therapy, and are expected to be an innovative model for NSCLC treatment

Genome-Wide Association Studies Reveal the Genetic Basis of Ionomic Variation in Rice

Rice (Oryza sativa) is an important dietary source of both essential micronutrients and toxic trace elements for humans. The genetic basis underlying the variations in the mineral composition, the ionome, in rice remains largely unknown. Here, we describe a comprehensive study of the genetic architecture of the variation in the rice ionome performed using genome-wide association studies (GWAS) of the concentrations of 17 mineral elements in rice grain from a diverse panel of 529 accessions, each genotyped at ∼6.4 million single nucleotide polymorphism loci. We identified 72 loci associated with natural ionomic variations, 32 that are common across locations and 40 that are common within a single location. We identified candidate genes for 42 loci and provide evidence for the causal nature of three genes, the sodium transporter gene Os-HKT1;5 for sodium, Os-MOLYBDATE TRANSPORTER1;1 for molybdenum, and Grain number, plant height, and heading date7 for nitrogen. Comparison of GWAS data from rice versus Arabidopsis (Arabidopsis thaliana) also identified well-known as well as new candidates with potential for further characterization. Our study provides crucial insights into the genetic basis of ionomic variations in rice and serves as an important foundation for further studies on the genetic and molecular mechanisms controlling the rice ionome

Distance between various discretized fermion actions

We present the leading order mixed-action effect $\Delta_{\rm mix}\equiv m_{\pi,{\rm vs}}^2-\frac{m_{\pi,{\rm vv}}^2+m_{\pi,{\rm ss}}^2}{2}$ using HISQ, clover or overlap valence fermion actions on the gauge ensembles with kinds of sea fermion actions among a widely used lattice spacing range $a\in [0.04,0.19]$~fm. The results suggest that $\Delta_{\rm mix}$ decreases on the forth order of the lattice spacing on the gauge ensembles with the dynamical chiral sea fermion, likes the Domain wall or HISQ fermion. When the clover sea fermion action which has explicit chiral symmetry breaking is used in the ensemble, $\Delta_{\rm mix}$ can be much larger regardless of the valence fermion action used

Distance between various discretized fermion actions

We present the leading order mixed-action effect $\Delta_{\rm mix}\equiv m_{\pi,{\rm vs}}^2-\frac{m_{\pi,{\rm vv}}^2+m_{\pi,{\rm ss}}^2}{2}$ using HISQ, clover or overlap valence fermion actions on the gauge ensembles with kinds of sea fermion actions among a widely used lattice spacing range $a\in [0.04,0.19]$~fm. The results suggest that $\Delta_{\rm mix}$ decreases on the forth order of the lattice spacing on the gauge ensembles with the dynamical chiral sea fermion, likes the Domain wall or HISQ fermion. When the clover sea fermion action which has explicit chiral symmetry breaking is used in the ensemble, $\Delta_{\rm mix}$ can be much larger regardless of the valence fermion action used

Distance between various discretized fermion actions

We present the leading order mixed-action effect $\Delta_{\rm mix}\equiv m_{\pi,{\rm vs}}^2-\frac{m_{\pi,{\rm vv}}^2+m_{\pi,{\rm ss}}^2}{2}$ using HISQ, clover or overlap valence fermion actions on the gauge ensembles with kinds of sea fermion actions among a widely used lattice spacing range $a\in [0.04,0.19]$~fm. The results suggest that $\Delta_{\rm mix}$ decreases on the forth order of the lattice spacing on the gauge ensembles with the dynamical chiral sea fermion, likes the Domain wall or HISQ fermion. When the clover sea fermion action which has explicit chiral symmetry breaking is used in the ensemble, $\Delta_{\rm mix}$ can be much larger regardless of the valence fermion action used

A Survey of Computing-in-Memory Processor: From Circuit to Application

The computing-in-memory (CIM) technique is emerging with the evolvement of big data and artificial intelligence (AI) application. The manuscript presents a systematic review of existing CIM works in a bottom-up view from circuit to application. Various types of CIM circuits based on different volatile/nonvolatile devices are introduced. The micro CIM architectures are illustrated to support multibit precision computation. After that, several types of processor-level CIM chips are analyzed to reveal the system architecture design considerations. The corresponding CIM tool chains and applications beyond AI applications are also introduced. From circuit to application levels, this manuscript analyzes the design tradeoffs, remained challenges, and possible future design trends at different design hierarchies of CIM processors

Kaon distribution amplitude from lattice QCD and the flavor SU(3) symmetry

We present the first lattice-QCD calculation of the kaon distribution amplitude using the large-momentum effective theory (LaMET) approach. The momentum-smearing technique has been implemented to improve signals at large meson momenta. We subtract the power divergence due to Wilson line to high precision using multiple lattice spacings. The kaon structure clearly shows an asymmetry of the distribution amplitude around x=1/2, a clear sign of its skewness. Our result also prefers a broader distribution than the asymptotic form. We also study the leading SU(3) flavor symmetry breaking relations for the pion, kaon and eta meson distribution amplitudes, and the results are consistent with the prediction from chiral perturbation theory

Unpolarized isovector quark distribution function from lattice QCD: a systematic analysis of renormalization and matching

Lattice Parton Collaboration (Liu, Yu-Sheng, et al.), "Unpolarized isovector quark distribution function from lattice QCD: a systematic analysis of renormalization and matching." Physical Review D 101 (Feb. 2020): no. 034020 doi 10.1103/PhysRevD.101.034020 ©2020 Author(s)We present a detailed lattice QCD study of the unpolarized isovector quark parton distribution function (PDF) using a large-momentum effective theory framework. We choose a quasi-PDF defined by a spatial correlator which is free from mixing with other operators of the same dimension. In the lattice simulation, we use a Gaussian-momentum-smeared source at M[subscript p]=356  MeV and P[subscript z]∈{1.8,2.3}  GeV. To control the systematics associated with the excited states, we explore five different source-sink separations. The nonperturbative renormalization is conducted in a regularization-independent momentum subtraction scheme, and the matching between the renormalized quasi-PDF and [line over MS] PDF is calculated based on perturbative QCD up to one-loop order. Systematic errors due to renormalization and perturbative matching are also analyzed in detail. Our results for light-cone PDF are in reasonable agreement with the latest phenomenological analysis. ©202

Nucleon Transversity Distribution in the Continuum and Physical Mass Limit from Lattice QCD

We report a state-of-the-art lattice QCD calculation of the isovector quark transversity distribution of the proton in the continuum and physical mass limit using large-momentum effective theory. The calculation is done at four lattice spacings a={0.098,0.085,0.064,0.049}  fm and various pion masses ranging between 220 and 350 MeV, with proton momenta up to 2.8 GeV. The result is nonperturbatively renormalized in the hybrid scheme with self-renormalization, which treats the infrared physics at large correlation distance properly, and extrapolated to the continuum, physical mass, and infinite momentum limit. We also compare with recent global analyses for the nucleon isovector quark transversity distribution