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Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple‐negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti‐cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the ubiquitin E3 ligase βTRCP in the form of molecular glue. C1 significantly inhibits the proliferation and metastasis of TNBC cells both in vitro and in vivo and in TNBC patient‐derived organoids, and these antitumor effects are attributed to the degradation of eEF2K by C1. Additionally, combination treatment of C1 with paclitaxel, a commonly used chemotherapeutic drug, exhibits synergistic anti‐tumor effects against TNBC. This study not only generates a powerful research tool to investigate the therapeutic potential of targeting eEF2K, but also provides a promising lead compound for developing novel drugs for the treatment of TNBC and other cancers. [ABSTRACT FROM AUTHOR]

The comparison and analysis of piezoelectric properties for [001]-oriented PMN-0.30PT by different polarization conditions were investigated. It should be noticed that the average piezoelectric coefficients d33 of PMN-0.30PT crystals were 1860 pC/N by alternating current (AC) polarization and 1380 pC/N by direct current (DC) polarization, which indicates a promotion of 35.3%. The domain patterns in the [001] surface of PMN-0.30PT single crystals under different polarization conditions are obtained by piezo-response force microscopy. The enhancement of piezoelectric performance by AC polarization is attributed to the regular stripe domains with high domain wall density. With the temperature increased to TR-T, both the values of dielectric constant ε r T and piezoelectric coefficients d33 under AC polarization condition maintain higher compared to traditional DC poled samples. In addition, both the values of e 33 and ε 33 S under AC polarization retain higher than that of DC polarization, suggesting that the special domain structure with high domain wall density by AC polarization keeps a stable state as the temperature increased to TR-T. When the temperature increased from TR-T to TT-C, the piezoelectric properties of crystals (ε r T and d33) under different polarization conditions become the same status, which indicates that the domain structure under the different conditions of polarization may tend to the similar state and the extrinsic contribution from the domain wall motion by AC polarization is disappeared. [ABSTRACT FROM AUTHOR]

High-Curie temperature (TC) piezoelectric ceramics 0.15Pb(Mg1/3Nb2/3)O3-0.38PbHfO3-0.47PbTiO3 (0.15PMN-0.38PH-0.47PT) were fabricated via the citrate method, which shows pure perovskite structure. The ceramics have composition locating at the rhombohedral side around the morphotropic phase boundary (MPB), and present enhanced electrical properties as compared with those prepared by the solid-state reaction method via the columbite precursor technique. Temperature-dependent Raman spectroscopy not only proves the occurrence of the ferroelectric to paraelectric phase transition around TC, but also detects the successive phase symmetry transitions, which correlate with the polar nanoregions (PNRs) or the coexistence of multiple ferroelectric phases. Large quantities of fine stripe nanoscale ferroelectric domains are observed by piezoresponse force microscopy (PFM) in the 0.15PMN-0.38PH-0.47PT ceramics, which form the larger micron island domains. Temperature-dependent Raman spectra and PFM results indicate that the excellent dielectric, ferroelectric and piezoelectric properties of the 0.15PMN-0.38PH-0.47PT ceramics can be attributed to either the existence of the PNRs with low symmetry or the multiple-ferroelectric-phases coexistence around room temperature and the fine stripe ferroelectric domains. [ABSTRACT FROM AUTHOR]

The [111]‐oriented rhombohedral Mn‐doped 0.15Pb(In1/2Nb1/2)‐0.55Pb(Mg1/3Nb2/3)O3‐0.30PbTiO3 (Mn:PIMNT(15/55/30)) crystal and the [001]‐oriented tetragonal Mn‐doped 0.29Pb(In1/2Nb1/2)‐0.29Pb(Mg1/3Nb2/3)O3‐0.42PbTiO3 (Mn:PIMNT(29/29/42)) crystal were poled under different conditions. The pyroelectric performance of the two crystals as a function of poling temperature, as well as the relationship with ferroelectric domain configuration and phase structure was investigated systematically. The pyroelectric properties of the two crystals enhance with rising the poling temperature, which can be attributed to the improvement of the single state. And for the rhombohedral Mn:PIMNT(15/55/30) crystal locating near morphotropic phase boundary (MPB), the increase of tetragonal phase induces the deterioration of pyroelectric properties. Due to more residual tetragonal phase, the pyroelectric coefficient of the Mn:PIMNT(15/55/30) crystal poled at 150°C is lower than that poled at 100°C. In general, both the crystals poled above TC achieve nearly single state, exhibiting the best pyroelectric properties with relatively high Curie temperature (TC), where P = 9.71 × 10−4 C m−2 K−1, Fi = 3.88 × 10−10 m V−1, Fv = 0.068 m2 C−1 and Fd = 29.7 × 10−5 Pa−1/2 for the rhombohedral Mn:PIMNT(15/55/30) crystal (TC = 171°C) and P = 6.78 × 10−4 C m−2 K−1, Fi = 2.71 ×10−10 mV−1, Fv = 0.1 m2 C−1, Fd = 23.54 × 10−5 Pa−1/2 for the tetragonal Mn:PIMNT(29/29/42) single crystal (TC = 251°C), meeting the stable operation of infrared detector at relatively high environmental temperatures. [ABSTRACT FROM AUTHOR]

The defects of the [001]-oriented grown 0.73Pb(Mg 1/3 Nb 2/3)O 3 -0.27PbTiO 3 (PMN-0.27PT) single crystals, as well as their influence on electrical properties, were studied by comparing the as-grown and annealed samples. Apart from the anomalies induced by the successive ferroelectric phase transitions, four relaxation processes of the as-grown PMN-0.27PT single crystals grown along [001] direction were discussed and determined by the dielectric spectroscopy, complex impedance spectroscopy, AC conductivity, suggesting the existence of many oxygen vacancies and lead vacancies in the as-grown samples. High-angle annular dark-field imaging of scanning transmission electron microscope (HAADF-STEM) was applied to observe the defects in atomic-scale. The point defects generated more easily when growing the PMNT crystals along [001] direction than along [111] direction can be attributed to the difference of growth mechanism and necessary growth environment induced by different growth directions, which results in the special coloration phenomenon of the [001]-oriented grown PMNT crystals. [ABSTRACT FROM AUTHOR]

The dielectric, ferroelectric and piezoelectric properties of the high-Curie temperature (high-T C ) 0.15Pb(Mg 1/3 Nb 2/3 )O 3 -0.38PbHfO 3 -0.47PbTiO 3 (0.15PMN-0.38PH-0.47PT) ceramics synthesized by three different methods were investigated. The 0.15PMN-0.38PH-0.47PT ceramics prepared by the partial oxalate route present the best electrical properties (T C = 291 °C, ε m = 28,937, P r = 32.89 μC/cm 2 , E c = 9.35 kV/cm, d 33 = 456.2 pC/N and K p = 67.2%) and excellent thermal stability of the piezoactivity properties under T C . Piezoresponse force microscopy (PFM) and confocal Raman microscopy (CRM) were employed to probe the nanoscale mechanism responsible for the performance difference of the 0.15PMN-0.38PH-0.47PT ceramics prepared by three different methods, disclosing the existence of the fine stripe domains, which make up the big island domains. The interplay between the macroscopic properties and nanoscopic domain structures of the 0.15PMN-0.38PH-0.47PT ceramics has been revealed. The better ferroelectric and piezoelectric response arise from the smaller domain size, which reduces the domain wall energy; whereas the higher coercive field E c detected by the polarization-electric field (P-E) loops results from the harder domain switching for the 0.15PMN-0.38PH-0.47PT ceramics prepared by the wet chemical synthesis techniques. [ABSTRACT FROM AUTHOR]

Great progress has been made in expanding the repertoire of genetically encoded fluorescent sensors for monitoring intracellular transition metals (TMs). This powerful toolkit permits dynamic and non-invasive detection of TMs with high spatial-temporal resolution, which enables us to better understand the roles of TM homeostasis in both physiological and pathological settings. Here we summarize the recent development of genetically encoded fluorescent sensors for intracellular detection of TMs such as zinc and copper, as well as heavy metals including lead, cadmium, mercury, and arsenic. [ABSTRACT FROM AUTHOR]

Domain configuration evolution with temperature of the unpoled [001]-oriented 0.32Pb(InNb)O-0.345Pb(MgNb)O-0.335PbTiO (0.32PIN-0.345PMN-0.335PT) single crystals was studied by the polarized light microscopy (PLM). The optical observation of the domain structures reveals the coexistence of polymorphic ferroelectric phases with mainly ferroelectric monoclinic phase at room temperature and the irreversible domain evolution upon thermal cycling, which induce the high piezoelectric response in such relaxor-based ferroelectric single crystals with the morphotropic phase boundary compositions combined with polarization rotation. The temperature dependent domain evolution and dielectric behavior demonstrate the successive temperature-induced second-order ferroelectric M phase to ferroelectric tetragonal (T) phase (FE-FE) and first-order ferroelectric T phase to paraelectric cubic (C) phase (FE-P) ferroelectric phase transitions in the unpoled 0.32PIN-0.345PMN-0.335PT single crystals. Two dielectric loss anomalies were detected around the dielectric anomaly below 100 °C in the poled 0.32PIN-0.345PMN-0.335PT single crystals, indicating that the FE-FE phase transition can be correlated with two different ferroelectric phase transitions, one is M-M, and the other is M-T phase transition. The FE-FE phase transition was confirmed further by the energy density measurement. The temperature dependent piezoelectric properties proved that the working temperature of the 0.32PIN-0.345PMN-0.335PT single crystals can reach 130 °C, higher around 50 °C than the Pb(MgNb)O-PbTiO single crystals, indicating their promising applications in transducers used at elevated temperatures. [ABSTRACT FROM AUTHOR]

Ferroelectric phase transition characteristic and electrical conduction mechanism of the high Curie-point (T C ) 0.15Pb(Mg 1/3 Nb 2/3 )O 3 −0.4PbHfO 3 −0.45PbTiO 3 (PMN-PHT) piezoelectric ceramics were studied by the temperature dependent Raman spectra and electrical properties. Sole first-order ferroelectric phase transition is demonstrated by the thermal hysteresis behavior of the temperature dependent dielectric constant and the dramatic drop of the derivative of inverse dielectric constant ξ= d(1/ε r )/dT around T C in the PMN-PHT ceramics. The temperature dependent Raman spectroscopy not only provides further evidence for the ferroelectric to paraelectric phase transition appearing around T C in the PMN-PHT ceramics, but also reveals the successive phase symmetry changes of the polar nanoregions (PNRs), in which apparent anomalies appear in the Raman peaks' wavenumber, wavenumber distance, intensity, intensity ratio, and line width of some selected Raman modes upon heating. Typical sole cole-cole circle is obtained for the PMN-PHT ceramics in the temperature range of 440–560 °C, based on which the activation energy (E a ) of the electrical conduction is calculated being ~1.2 eV. Such low value of E a indicates that the oxygen vacancies formed in the PHT-PMN ceramics induced by the evaporation of Pb during the sintering process dominate the high-temperature extrinsic electrical conduction. [ABSTRACT FROM AUTHOR]

The ferroelectric phase transition characteristics of the 0.32Pb(In1/2Nb1/2)O3-0.345Pb(Mg1/3Nb2/3)O3-0.335PbTiO3(0.32PIN-0.345PMN-0.335PT) single crystals were studied by the temperature-dependent Raman spectroscopy and some electrical properties. Ferroelectric monoclinic phase was confirmed at room temperature by the numbers of the Raman modes. Successive ferroelectric phase transitions, i.e. ferroelectric monoclinic phase to ferroelectric tetragonal phase transition (FEM-FET) and ferroelectric tetragonal phase to paraelectric cubic phase transition (FET-PC), are evidenced by the anomalies of Raman modes line width, peaks intensity and their ratios aroundTM-TandTC/Tmtemperatures. The temperature dependent permittivity derivative ξ =dϵ/dTnot only provides further evidence of the successive ferroelectric phase transitions, but also demonstrates the second-order transition characteristic of the FEM-FETphase transition and the first-order transition feature of the FET-PCphase transition. The FEM-FETphase transition is also confirmed by the abnormal narrowing of the P-E loops, decrease of thePrandEcvalues, and extremums of the pyroelectric performance. [ABSTRACT FROM PUBLISHER]

The widely conserved multiple antibiotic resistance regulator (MarR) family of transcription factors modulates bacterial detoxification in response to diverse antibiotics, toxic chemicals or both. The natural inducer for Escherichia coli MarR, the prototypical transcription repressor within this family, remains unknown. Here we show that copper signaling potentiates MarR derepression in E. coli. Copper(II) oxidizes a cysteine residue (Cys80) on MarR to generate disulfide bonds between two MarR dimers, thereby inducing tetramer formation and the dissociation of MarR from its cognate promoter DNA. We further discovered that salicylate, a putative MarR inducer, and the clinically important bactericidal antibiotics norfloxacin and ampicillin all stimulate intracellular copper elevation, most likely through oxidative impairment of copper-dependent envelope proteins, including NADH dehydrogenase-2. This membrane-associated copper oxidation and liberation process derepresses MarR, causing increased bacterial antibiotic resistance. Our study reveals that this bacterial transcription regulator senses copper(II) as a natural signal to cope with stress caused by antibiotics or the environment. [ABSTRACT FROM AUTHOR]

Mn:0.15Pb(In1/2Nb1/2)O3-0.55Pb(Mg1/3Nb2/3)O3-0.30PbTiO3 (Mn:PIMNT) pyroelectric chips were prepared by a two-step annealing method. For the two steps, annealing temperatures dependence of microstructure, defects, surface stress, surface roughness, dielectric properties and pyroelectric properties were studied comprehensively. The controlling factors influencing the pyroelectric properties of the Mn:PIMNT crystals were analyzed and the optimum annealing temperature ranges for the two steps were determined: 600–700 °C for the first step and 500–600 °C for the second step. The pyroelectric properties of the thin Mn:PIMNT chips were significantly enhanced by the two-step annealing method via tuning oxygen vacancies and eliminating surface stress. Based on Mn:PIMNT pyroelectric chips annealed at the most favorable conditions (annealed at 600 °C for the first step and 500 °C for the second step), infrared detectors were prepared with specific detectivity D* = 1.63 × 109 cmHz1/2W−1, nearly three times higher than in commercial LiTaO3 detectors. [ABSTRACT FROM AUTHOR]

Dielectric, piezoelectric, and ferroelectric properties of [001]‐oriented Mn‐0.15PIN‐0.55PMN‐0.30PT crystal are studied as functions of temperature. The single crystal exhibits excellent piezoelectric properties (d33 ~ 1330 pC N−1), higher ferroelectric to ferroelectric phase transition temperature (TR‐M ~ 112 °C), and larger coercive field (Ec ≈4.5 kV cm−1) than the binary PMN‐PT with morphotropic phase boundary compositions. Temperature‐induced phase transition characteristics of Mn‐0.15PIN‐0.55PMN‐0.30PT crystal are investigated by the temperature‐dependence Raman spectroscopy, and the temperature‐dependent electrical properties analysis shows that the values of Smax%, Q, and d33* are significantly dependent on the ferroelectric phase transitions. The results are beneficial to deeply understand the relationships between structure and properties in ternary Mn‐0.15PIN‐0.55PMN‐0.30PT single crystals. [ABSTRACT FROM AUTHOR]

The piezoelectric properties of the high-Curie temperature (high-TC) 0.15Pb(Mg1/3Nb2/3)O3-0.38PbHfO3-0.47PbTiO3 (0.15PMN-0.38PH-0.47PT) ceramics prepared by three different methods were compared. The 0.15PMN-0.38PH-0.47PT ceramics synthesized by the partial oxalate route exhibit the optimum properties, in which d33* = 845.3 pm/V, d33 = 456.2 pC/N, Kp = 67.2%, and TC = 291 °C. The nanoscale origin of the high piezoelectric response of the 0.15PMN-0.38PH-0.47PT ceramics was investigated by piezoresponse force microscopy (PFM) using the ceramics synthesized by the partial oxalate route. Large quantities of fine stripe submicron ferroelectric domains are observed, which form large island domains. In order to give further insights into the piezoelectric properties of the 0.15PMN-0.38PH-0.47PT ceramics from a microscopic point of view, the local poling experiments and local switching spectroscopy piezoresponse force microscopy (SS-PFM) were investigated, from which the local converse piezoelectric coefficient d33*(l) is calculated as 220 pm/V. [ABSTRACT FROM AUTHOR]

In this paper, the 0.15Pb(Mg 1/3 Nb 2/3)O 3 -0.38PbHfO 3 -0.47PbTiO 3 ternary piezoelectric ceramic fabricated by the partial oxalate method that exhibits superior electrical properties (d 33 = 447 pC/N and k t = 56.9%) and excellent thermal stability of the piezoelectric properties below T C was studied. The newly discovered piezoelectric ceramic had a high Curie temperature (T m = 297 °C), this feature was used to fabricate a novel single-element ultrasonic transducer whose center frequency was 2.15 MHz, with a −6 dB bandwidth of up to 79.07%, and a sensitivity that reached −31.75 dB. The result of the experiment agreed well with that of PiezoCAD software based on the KLM model. This transducer's outstanding thermal stability below T C can be widely used in non-destructive evaluation. At the same time, we measured the sound field distribution of the ultrasonic transducer. The focal length was measured approximately 47 mm. An obvious main lobe was clearly seen from the z–x scan. The power was measured as 17.98 mW; the beam width of –3dB was 3.5 × 3.6 mm; and the area was 9.83 mm2 according to the FDA and IEC standards. [ABSTRACT FROM AUTHOR]

A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and β -hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr′s gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the "metabolites-modification-regulation" axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones. [Display omitted] • SiTomics uses genetic code expansion combined with proteomic and genomic profiling • In situ and multi-dimensional identification of chromatinized interactome • Linkage between the interacting proteome and genome via dynamic H3K56 acylations • A role of super-enhancers along the "metabolites-modification-regulation" axis A genetic code expansion approach enables functional characterization of site-specific changes and interactome of histone lysine modifications in response to short chain fatty acid stimulations, linking the location of the modified nucleosomes with associated proteins on the physiological chromatin. [ABSTRACT FROM AUTHOR]

Necroptosis induction in vitro often requires caspase-8 (Casp8) inhibition by zVAD because pro-Casp8 cleaves RIP1 to disintegrate the necrosome. It has been unclear how the Casp8 blockade of necroptosis is eliminated naturally. Here, we show that pro-Casp8 within the necrosome can be inactivated by phosphorylation at Thr265 (pC8T265). pC8T265 occurs in vitro in various necroptotic cells and in the cecum of TNF-treated mice. p90 RSK is the kinase of pro-Casp8. It is activated by a mechanism that does not need ERK but PDK1, which is recruited to the RIP1-RIP3-MLKL-containing necrosome. Phosphorylation of pro-Casp8 at Thr265 can substitute for zVAD to permit necroptosis in vitro. pC8T265 mimic T265E knockin mice are embryonic lethal due to unconstrained necroptosis, and the pharmaceutical inhibition of RSK-mediated pC8T265 diminishes TNF-induced cecum damage and lethality in mice by halting necroptosis. Thus, phosphorylation of pro-Casp8 at Thr265 by RSK is an intrinsic mechanism for passing the Casp8 checkpoint of necroptosis. • Phosphorylation of pro-caspase-8 at Thr265 releases the blockade of necroptosis • RSK phosphorylates pro-caspase-8 at Thr265 in the necrosome • PDK1 activates RSK by an ERK-independent mechanism to promote necroptosis • RSK inhibition protects mice from TNF-induced cecum injury and lethality An intrinsic mechanism—RSK, activated by TNF via PDK1—for overcoming necroptosis blockade is revealed by Yang et al. that phosphorylates pro-caspase-8 at Thr265 within the necrosome to inactivate pro-caspase-8. [ABSTRACT FROM AUTHOR]

eEF2K, an atypical alpha-kinase, is responsible for regulating protein synthesis and energy homeostasis. Aberrant eEF2K function has been linked to various human cancers, including triple-negative breast cancer (TNBC). However, limited cellular activity of current eEF2K modulators impedes their clinical application. Based on the 2-phenyl-1,2,4-triazine-3,5(2 H ,4 H )-dione scaffold of our hits I4 and C1 , structure-activity relationship analysis led to the discovery of several more active derivatives (e.g., 19 , 34 , and 36 ) in inhibiting the viability of TNBC cell line MDA-MB-231. Moreover, the most potent compound 36 significantly suppresses the viability, proliferation, and migration of both MDA-MB-231 and HCC1806 cell lines. Mechanistically, compound 36 has a high binding affinity for the eEF2K protein and effectively induces its degradation. Additionally, 36 exerts a comparable tumor-suppressive effect to paclitaxel in an MDA-MB-231 cell xenograft mouse model with no obvious toxicity, demonstrating that compound 36 could be developed as a potential novel therapeutic for TNBC treatment.

The 1 wt % Li-doped (Ba 0.85 Ca 0.15 )(Zr 0.1 Ti 0.9 )O₃ (BCZT-Li) ceramics prepared by the citrate method exhibit improved phase purity, densification and electrical properties, which provide prospective possibility to develop high-performance electrocaloric materials. The electrocaloric effect was evaluated by phenomenological method, and the BCZT-Li ceramics present large electrocaloric temperature change ∆ T , especially large electrocaloric responsibility ξ = ∆ T max /∆ E max , which can be comparable to the largest values reported in the lead-free piezoelectric ceramics. The excellent electrocaloric effect is considered as correlating with the coexistence of polymorphic ferroelectric phases, which are detected by the Raman spectroscopy. The large ξ value accompanied by decreased Curie temperature (around 73 °C) of the BCZT-Li ceramics prepared by the citrate method presents potential applications as the next-generation solid-state cooling devices., Competing Interests: The authors declare no conflict of interest.

Posttranslational modifications (PTMs) of lysine are crucial histone marks that regulate diverse biological processes. The functional roles and regulation mechanism of many newly identified lysine PTMs, however, remain yet to be understood. Here we report a photoaffinity crotonyl lysine (Kcr) analogue that can be genetically and site-specifically incorporated into histone proteins. This, in conjunction with the genetically encoded photo-lysine as a "control probe", enables the capture and identification of enzymatic machinery and/or effector proteins for histone lysine crotonylation.

Astragaloside IV is a monomer isolated from Astragalus membranaceus (Fisch.) Bunge, which is one of the most widely used plant-derived drugs in traditional Chinese medicine for diabetes therapy. In the present study, we aimed to examine the effects of astragaloside IV on glucose in C2C12 myotubes and the underlying molecular mechanisms responsible for these effects. Four-day differentiated C2C12 myotubes were exposed to palmitate for 16 h in order to establish a model of insulin resistance and 3H glucose uptake, using 2-Deoxy‑D‑[1,2-3H(N)]-glucose (radiolabeled 2-DG), was detected. Astragaloside IV was added 2 h prior to palmitate exposure. The translocation of glucose transporter 4 (GLUT4) was evaluated by subcellular fractionation, and the expression of insulin signaling molecules such as insulin receptor β (IRβ), insulin receptor substrate (IRS)1/protein kinase B (AKT) and inhibitory κB kinase (IKK)/inhibitor-κBα (IκBα), which are associated with insulin signal transduction, were assessed in the basal or the insulin‑stimulated state using western blot analysis or RT-PCR. We also examined the mRNA expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and Toll‑like receptor 4 (TLR4). Taken together, these findings demonstrated that astragaloside IV facilitates glucose transport in C2C12 myotubes through a mechanism involving the IRS1/AKT pathway, and suppresses the palmitate-induced activation of the IKK/IκBα pathway.

Heme plays pivotal roles in various cellular processes as well as in iron homeostasis in living systems. Here, we report a genetically encoded fluorescence resonance energy transfer (FRET) sensor for selective heme imaging by employing a pair of bacterial heme transfer chaperones as the sensory components. This heme-specific probe allows spatial-temporal visualization of intracellular heme distribution within living cells.