Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration of metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic ...strategies. Here, we integrated the multiomics data of our large TNBC cohort (n = 465) to develop the ferroptosis atlas. We discovered that TNBCs had heterogeneous phenotypes in ferroptosis-related metabolites and metabolic pathways. The luminal androgen receptor (LAR) subtype of TNBC was characterized by the upregulation of oxidized phosphatidylethanolamines and glutathione metabolism (especially GPX4), which allowed the utilization of GPX4 inhibitors to induce ferroptosis. Furthermore, we verified that GPX4 inhibition not only induced tumor ferroptosis but also enhanced antitumor immunity. The combination of GPX4 inhibitors and anti-PD1 possessed greater therapeutic efficacy than monotherapy. Clinically, higher GPX4 expression correlated with lower cytolytic scores and worse prognosis in immunotherapy cohorts. Collectively, this study demonstrated the ferroptosis landscape of TNBC and revealed an innovative immunotherapy combination strategy for refractory LAR tumors.
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•Integrated analysis systematically demonstrates the ferroptosis heterogeneity in TNBC•LAR subtype of TNBC is hypersensitive to ferroptosis inducers, especially GPX4 inhibitors•AR plays a dual role in regulating ferroptosis of LAR tumors•Combination of GPX4 inhibitors and immunotherapy is an option for LAR tumors
Yang et al. systematically demonstrated the ferroptosis heterogeneity in triple-negative breast cancer (TNBC). They found that luminal androgen receptor (LAR) subtype of TNBC was hypersensitive to ferroptosis inducers and revealed that the combination of GPX4 inhibitors and immune checkpoint inhibitors was a novel treatment strategy for LAR TNBCs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
5‐Formylcytidine (f5C) is one of the epigenetic nucleotides in tRNA. Despite the evident importance of f5C in gene expression regulation, little is known about its exact amount and position. To ...capture this information, we developed a modification‐specific functionalization with a semi‐stabilized ylide. The chemical labelling exhibited a high selectivity towards f5C and allowed distinction from similar 5‐formyluridine. We realized a detection strategy based on the fluorescence signal of the cyclization product 4,5‐pyridin‐2‐amine‐cytidine paC, which exhibited a high quantum yield. The results clearly identified f5C with a limit of detection at 0.58 nM. This method altered the hydrogen bonding activities of f5C and modulated its reverse transcription signature in its sequencing profile. We showed that f5C can be detected from tRNA segments with a single‐base resolution. Taken together, this approach is a sensitive, antibody‐free, and applicable detection and sequencing method for f5C‐containing RNA.
The tandem Wittig‐cyclization reaction was initiated with the use of triphenyl phosphonium ylide under light irradiation for the chemical labelling of 5‐formylcytidine f5C RNA, making it possible to detect trace amount of f5C in cell lysates and to develop a new sequencing strategy named paC‐Seq for cytosine in a single‐base resolution.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Pollution by heavy metals limits the area of land available for cultivation of food crops. A potential solution to this problem might lie in the molecular breeding of food crops for phytoremediation ...that accumulate toxic metals in straw while producing safe and nutritious grains. Here, we identify a rice quantitative trait locus we name cadmium (Cd) accumulation in leaf 1 (CAL1), which encodes a defensin-like protein. CAL1 is expressed preferentially in root exodermis and xylem parenchyma cells. We provide evidence that CAL1 acts by chelating Cd in the cytosol and facilitating Cd secretion to extracellular spaces, hence lowering cytosolic Cd concentration while driving long-distance Cd transport via xylem vessels. CAL1 does not appear to affect Cd accumulation in rice grains or the accumulation of other essential metals, thus providing an efficient molecular tool to breed dual-function rice varieties that produce safe grains while remediating paddy soils.
Highly efficient electrocatalysts with high intrinsic activity for oxygen and sulfur redox reactions are strongly required for sustainable energy systems. Generally, cations serve as the real active ...sites in transition metal compound electrocatalysts, whose electrocatalytic activity is regulated by the surrounding anionic structure. Herein, an electrochemical reaction assisted by an anionic regulation strategy is proposed for precise construction of advanced electrocatalysts with extraordinary electrocatalytic activity. The electrochemical anionic regulation process ensures general release of the regulation reagents for precise substitution of sulfur anions in pristine hydroxide. The as-obtained hydroxysulfide electrocatalyst exhibits a desired electronic structure to afford superb electrocatalytic activity regarding reduced overpotential of 286 mV at 10 mA cm
−2
for electrocatalytic oxygen evolution and improved polysulfide redox electrocatalytic activity. This contribution not only renders an emerging strategy for precise regulation of the anionic structure for improved electrocatalytic activity, but also provides information for the rational design of advanced electrocatalysts for sustainable energy applications.
An electrochemical reaction assisted by an anionic regulation strategy was proposed for precise construction of hetero-anionic electrocatalysts for oxygen evolution and polysulfide redox reactions.
We model the newly synthesized magic-angle-twisted bilayer graphene superconductor with two p_{x,y}-like Wannier orbitals on the superstructure honeycomb lattice, where the hopping integrals are ...constructed via the Slater-Koster formulism by symmetry analysis. The characteristics exhibited in this simple model are well consistent with both the rigorous calculations and experiment observations. A van Hove singularity and Fermi-surface (FS) nesting are found in the doping levels relevant to the correlated insulator and unconventional superconductivity revealed experimentally, based on which we identify the two phases as weak-coupling FS instabilities. Then, with repulsive Hubbard interactions turned on, we performed random-phase-approximation based calculations to identify the electron instabilities. As a result, we find chiral d+id topological superconductivity bordering the correlated insulating state near half-filling, identified as noncoplanar chiral spin-density wave ordered state, featuring the quantum anomalous Hall effect. The phase diagram obtained in our approach is qualitatively consistent with experiments.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Kiwifruit (Actinidia spp.) is a climacteric fruit with high sensitivity to ethylene, influenced by multiple ethylene-responsive structural genes and transcription factors. However, the roles of other ...post-transcriptional regulators (e.g. miRNAs) necessary for ripening remain elusive.
High-throughput sequencing sRNAome, degradome and transcriptome methods were used to identify further contributors to ripening control in the kiwifruit (A. deliciosa cv ‘Hayward’).
Two NAM/ATAF/CUC domain transcription factors (AdNAC6 and AdNAC7), both predicted targets for miR164, showed significant upregulation by exogenous ethylene. Gene expression analysis and luciferase reporter assays indicated that Ade-miR164 and one of its precursor miRNAs (Ade-MIR164b) were repressed by ethylene treatment and negatively correlated with AdNAC6/7 expression. Subsequent analysis indicated that both AdNAC6 and AdNAC7 proteins are transcriptional activators and physically bind the promoters of AdACS1 (1-aminocyclopropane-1-carboxylate synthase), AdACO1 (1-aminocyclopropane-1-carboxylic acid oxidase), AdMAN1 (endo-β-mannanase) and AaTPS1 (terpene synthase). Moreover, subcellular analysis indicated that the location of the AdNAC6/7 proteins was influenced by Ade-miR164.
Multiple omics-based approaches revealed a novel regulatory link for fruit ripening that involved ethylene-miR164-NAC. The regulatory pathway for miR164-NAC is present in various fruit (e.g. Rosaceae fruit, citrus, grape), with implications for fruit ripening regulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Business process management (BPM) aims to optimize business processes to achieve better system performance such as higher profit, quicker response, and better services. BPM systems in Industry 4.0 ...are required to digitize and automate business process workflows and support the transparent interoperations of service vendors. The critical bottleneck to advance BPM systems is the evaluation, verification, and transformation of trustworthiness and digitized assets. Most of BPM systems rely heavily on domain experts or third parties to deal with trustworthiness. In this paper, an automated BPM solution is investigated to select and compose services in open business environment, Blockchain technology (BCT) is explored and proposed to transfer and verify the trustiness of businesses and partners, and a BPM framework is developed to illustrate how BCT can be integrated to support prompt, reliable, and cost-effective evaluation and transferring of Quality of Services in the workflow composition and management.
A nonsymmetric salamo-like ligand (H2L, 5-(N,N′-diethylamino)-2,2′-ethylenedioxybis(nitrilomethylidyne)phenolnaphthol) has been synthesized, and its two homotrinuclear complexes ...{Zn3(L)2(μ-OAc)2}2·5EtOH and Ni3(L)2(μ-OAc)2(MeOH)2·2MeOH and single crystals of the ligand have been successfully synthesized and characterized structurally. Molecular electrostatic potential analysis, interaction region indicator analysis, Hirshfeld surfaces analyses, DFT calculations and fluorescent properties of the Zn(Ⅱ) and Ni(Ⅱ) complexes were also studied.
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•Single crystals of H2L and its Zn(II) and Ni(II) complexes have been determined.•The Zn(II) complex possesses two crystallographically and chemically identical trinuclear clusters.•Experimental and theoretical investigation of the Zn(II) and Ni(II) complexes were performed.
Neutral homotrinuclear complexes {Zn3(L)2(μ-OAc)2}2·5EtOH and Ni3(L)2(μ-OAc)2(MeOH)2·2MeOH were obtained in the reactions of a new non-symmetric salamo-like ligand H2L (5-(N,N′-diethylamino)-2,2′-ethylenedioxybis(nitrilomethylidyne)phenolnaphthol) with the respective salts of M(OAc)2·2H2O (M = Zn(II) and Ni(II)), respectively. Single crystals of the ligand were also obtained. All the Zn(Ⅱ) and Ni(Ⅱ) complexes were structurally characterized by single crystal X-ray diffraction. Both Zn(Ⅱ) and Ni(Ⅱ) complexes are composed of two (L)2− units combined with three metal(Ⅱ) ions, where a pair of μ-OAc− ions bridging Zn1⋯Zn2 and Zn2⋯Zn3 or Ni1⋯Ni2 and Ni2⋯Ni1#1 neutralize the charge of the Zn(II) and Ni(II) complexes and stabilize the trinuclear structure. The two μ-OAc− ions are located on the same side of the Zn(Ⅱ) complex, while on different sides of the Ni(Ⅱ) complex. In addition, there are two methanol molecules in the Ni(Ⅱ) complex involved in the coordination. UV–vis absorption spectral analyses showed that the ligand (L)2− units have coordinated with Zn(Ⅱ) and Ni(Ⅱ) atoms. DFT calculations exhibited that the Zn(II) and Ni(II) complexes have higher kinetic stability and lower chemical reactivity. Fluorescence spectrum analyses indicated that the electrons of the ligand have transferred to the empty orbitals (LMCT) of the Zn(Ⅱ) and Ni(Ⅱ) atoms. Furthermore, to discern the interactions in the crystal structures, Hirshfeld surfaces analyses were evaluated. Molecular electrostatic potentials were calculated in order to find electrophilic and nucleophilic sites favorable for hydrogen bonds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The survival of allogeneic fetuses during pregnancy is a rather paradoxical phenomenon with a complex mechanism. Chemokine ligand12 (CXCL12) and its receptors CXC chemokine receptor (CXCR)4 and 7 are ...extensively found in placenta tissues and cells, including trophoblast cells, vascular endothelial cells, and decidual stromal and decidual immune cells (eg, NK cells and regulatory T cells). Evidence has illustrated that the CXClL12/CXCR4/CXCR7 axis could enhance the cross talk at the maternal‐fetal interface through multiple processes, such as invasion and placental angiogenesis, which appears to be critical signaling components in placentation and fetal outcome. In addition, an increasing number of studies have demonstrated that the CXCL12/CXCR4/CXCR7 axis also stands out for its pleiotropic roles in several pregnancy‐associated diseases (eg, recurrent spontaneous abortion (RSA), pre‐eclampsia (PE), and preterm labor). In the present review, the different biological properties and signaling in physiological and pathological pregnancy conditions of CXCL12/CXCR4/CXCR7 axis were discussed, with the aim of obtaining a further understanding of the regulatory mechanisms and highlighting their potential as a target for therapeutic approaches.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
As one of emerging technologies, Internet of Things (IoT) has become popular. This article reviews the literature regarding resource allocation (RA) of the Internet of Things systematically. It ...identifies the key techniques, state-of-the-art, challenges, and trend associated with the IoT resource allocation, and its impact on the enterprise architecture.
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