Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated ...cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the cholesterol-biosynthesis program and an attractive target for TNBC.
The first enantioselective aza‐Darzens reaction of cyclic imines with α‐halogenated ketones was realized under mild reaction conditions by using amino‐acid‐derived bifunctional phosphonium salts as ...phase‐transfer promoters. A variety of structurally dense tri‐ and tetrasubstituted aziridine derivatives, containing benzofused heterocycles as well as spiro‐structures, were readily synthesized in high yields with excellent diastereo‐ and enantioselectivities (up to >20:1 d.r. and >99.9 % ee). The highly functionalized aziridine products could be easily transformed into different classes of biologically active compounds.
Pinch of salt: A highly enantioselective aza‐Darzens cyclization between cyclic imines and α‐halogenated ketones catalyzed by amino‐acid‐derived bifunctional phosphonium salts has been developed. A wide range of enantioenriched fused tri‐ and tetrasubstituted aziridines were synthesized with high yields and excellent diastereo‐ and enantioselectivities. Scale‐up synthesis and valuable transformations are also demonstrated.
Based on the synergy between MoP and N-doped carbon, MoP nanoparticles encapsulated in N-doped carbon hollow spheres were synthesized using inorganic-organic hybrids as precursors, which shows an ...excellent stability and activity with an overpotential 96 mV at 10 mA cm−2 and a small Tafel slope of 53 mV dec−1 in alkaline solution.
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•A template-free approach was developed to fabricate MoP@NC hollow microsphere.•Inorganic-organic hybrids were used as precursors.•Remarkable electrocatalytic hydrogen evolution performance could be achieved.•The synergy between MoP and the pyridinic N could optimize the electronic structure.
Encapsulating transition metal phosphides into nitrogen-doped carbon (NC) materials is an effective strategy to enhance the electrocatalytic performance. Herein, we develop a novel template-free approach to rationally fabricate molybdenum phosphide (MoP) nanoparticles encapsulated in N-doped carbon (MoP@NC) hollow microspheres for alkaline hydrogen evolution reaction (HER) by employing inorganic-organic hybrids as precursors, in which phosphorus source of the MoP@NC derives from tetra (hydroxymethyl) phosphorus chloride for the first time. The optimized MoP@NC sample shows a low overpotential of 96 mV at 10 mA cm−2, a small Tafel slope of 53 mV dec−1, and excellent stability. The enhanced HER performance is mainly attributed to the integrated effects of a distinctive hollow structure, high pyridinic N-doping level, and the extremely intimate synergy between MoP and NC. Theoretical calculations indicate that the active sites of the catalyst are mainly located at Mo atoms adjacent to the pyridinic N-doped carbon layer (pyridinic-N-MoP); the synergistic interaction between MoP and pyridinic N (rather than pyrrolic or graphitic N) atoms can lower the d band center of Mo, weaken the Mo-Hads bond and thereby enhance HER performance. In addition, the pyridinic N atoms at the interactive sites play a key role in adsorbing H2O and preventing the adsorption of OH*, resulting in accelerating the water splitting. This work provides a new method to rationally synthesize high-efficient and stable MoP-based hollow sphere electrocatalysts for alkaline HER through designing inorganic-organic hybrid precursors.
Reported herein is an asymmetric 3+2 cycloaddition reaction of azomethine ylides with β‐trifluoromethyl β,β‐disubstituted enones, a reaction which is enabled by a Ming‐Phos‐derived copper(I) catalyst ...(Ming‐Phos=chiral sulfinamide monophosphines, Figure ). This method provides scalable and efficient access to the highly substituted pyrrolidines with a trifluoromethylated, all‐carbon quaternary stereocenter in good yields with up to greater than 20:1 d.r. and 98 % ee. The reaction has a broad substrate scope and tolerates a wide range of functional groups.
Out on pyrrol(idine): An asymmetric 3+2 cycloaddition reaction of azomethine ylides with β‐trifluoromethyl β,β‐disubstituted enones is enabled by the copper(I) catalyst with Ming‐Phos ligand. The highly substituted product pyrrolidines, having a trifluoromethylated, all‐carbon quaternary stereocenter, are isolated in good yields with up to greater than 20:1 d.r. and 98 % ee.
An improved understanding of the origin of the electrocatalytic activity is of importance to the rational design of highly efficient electrocatalysts for the hydrogen evolution reaction. Here, an ...ambipolar single‐crystal tungsten diselenide (WSe2) semiconductor is employed as a model system where the conductance and carrier of WSe2 can be individually tuned by external electric fields. The field‐tuned electrochemical microcell is fabricated based on the single‐crystal WSe2 and the catalytic activity of the WSe2 microcell is measured versus the external electric field. Results show that WSe2 with electrons serving as the dominant carrier yields much higher activity than WSe2 with holes serving as the dominant carrier even both systems exhibit similar conductance. The catalytic activity enhancement can be characterized by the Tafel slope decrease from 138 to 104 mV per decade, while the electron area concentration increases from 0.64 × 1012 to 1.72 × 1012 cm−2. To further understand the underlying mechanism, the Gibbs free energy and charge distribution for adsorbed hydrogen on WSe2 versus the area charge concentration is systematically computed, which is in line with experiments. This comprehensive study not only sheds light on the mechanism underlying the electrocatalysis processes, but also offers a strategy to achieve higher electrocatalytic activity.
An ambipolar single‐crystal tungsten diselenide (WSe2) semiconductor electrocatalyst is employed as a benchmark system for interfacial model catalysis. By tuning the external electric field, the conductance and carrier of ambipolar WSe2 can be individually modulated. Combining the experimental and theoretical study, it is demonstrated that the electron carrier plays a key role in the hydrogen evolution reaction.
Comprehensive phenotypic profiling of heterogeneous circulating tumor cells (CTCs) at single‐cell resolution has great importance for cancer management. Herein, a novel spectrally combined encoding ...(SCE) strategy was proposed for multiplex biomarker profiling of single CTCs using a multifunctional nanosphere‐mediated microfluidic platform. Different cellular biomarkers uniquely labeled by multifunctional nanosphere barcodes, possessing identical magnetic tags and distinct optical signatures, enabled isolation of heterogeneous CTCs with over 91.6 % efficiency and in situ SCE of phenotypes. By further trapping individual CTCs in ordered microstructures on chip, composite single‐cell spectral signatures were conveniently and efficiently obtained, allowing reliable spectral‐readout for multiplex biomarker profiling. This SCE strategy exhibited great potential in multiplex profiling of heterogeneous CTC phenotypes, offering new avenues for cancer study and precise medicine.
A spectrally combined encoding strategy was proposed for multiplex biomarker profiling of heterogeneous circulating tumor cells (CTCs) using a multifunctional nanosphere‐mediated microfluidic platform. Different cellular biomarkers simultaneously encoded with both magnetic tags and distinct optical signatures, enabled efficient isolation and in situ on‐chip spectrally combined encoding of heterogeneous CTCs at single‐cell resolution.
: Head and neck squamous cell carcinoma (HNSCC) are head and neck cancers. On the other hand, ferroptosis is a novel iron-dependent and ROS reliant type of cell death observed various disease ...conditions.
: We constructed a prognostic multilncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HNSCC.
: We identified 25 differently expressed lncRNAs associated with prognosis of HNSCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HNSCC. Moreover, the AUC of the lncRNAs signature was 0.782, underscoring their utility in prediction HNSCC prognosis. Indeed, our risk assessment model was superior to traditional clinicopathological features in predicting HNSCC prognosis. GSEA revealed the immune and tumor-related pathways in the low risk group individuals. Moreover, TCGA revealed T cell functions including cytolytic activity, HLA, regulation of inflammationp, co-stimulation, co-inhibition and coordination of type II INF response were significantly different between the low-risk and high-risk groups. Immune checkpoints such as PDCD-1 (PD-1), CTLA4 and LAG3, were also expressed differently between the two risk groups.
A novel ferroptosis-related lncRNAs signature impacts on the prognosis of HNSCC.
2D materials hold great potential for designing novel electronic and optoelectronic devices. However, 2D material can only absorb limited incident light. As a representative 2D semiconductor, ...monolayer MoS2 can only absorb up to 10% of the incident light in the visible, which is not sufficient to achieve a high optical‐to‐electrical conversion efficiency. To overcome this shortcoming, a “gap‐mode” plasmon‐enhanced monolayer MoS2 fluorescent emitter and photodetector is designed by squeezing the light‐field into Ag shell‐isolated nanoparticles–Au film gap, where the confined electromagnetic field can interact with monolayer MoS2. With this gap‐mode plasmon‐enhanced configuration, a 110‐fold enhancement of photoluminescence intensity is achieved, exceeding values reached by other plasmon‐enhanced MoS2 fluorescent emitters. In addition, a gap‐mode plasmon‐enhanced monolayer MoS2 photodetector with an 880% enhancement in photocurrent and a responsivity of 287.5 A W−1 is demonstrated, exceeding previously reported plasmon‐enhanced monolayer MoS2 photodetectors.
By dropping Ag shell‐isolated nanoparticles onto Al2O3‐covered Au film, the gap‐mode plasmonic structure with a gap thickness of 7 nm can form naturally. By integrating monolayer MoS2 into this plasmonic structure, 110‐fold photoluminescence and 880% photocurrent enhancement are achieved. This work shows that the gap‐mode plasmonic structures have huge potential for realizing high‐performance 2D‐material‐based optoelectronic devices.
Lithium (Li) metal with high theoretical capacity and low electrochemical potential is the most ideal anode for next-generation high-energy batteries. However, the practical implementation of Li ...anode has been hindered by dendritic growth and volume expansion during cycling, which results in low Coulombic efficiency (CE), short lifespan, and safety hazards. Here, we report a highly stable and dendrite-free Li metal anode by utilizing N-doped hollow porous bowl-like hard carbon/reduced graphene nanosheets (CB@rGO) hybrids as three-dimensional (3D) conductive and lithiophilic scaffold host. The lithiophilic carbon bowl (CB) mainly works as excellent guides during the Li plating process, whereas the rGO layer with high conductivity and mechanical stability maintains the integrity of the composite by confining the volume change in long-range order during cycling. Moreover, the local current density can be reduced due to the 3D conductive framework. Therefore, CB@rGO presents a low lithium metal nucleation overpotential of 18 mV, high CE of 98%, and stable cycling without obvious voltage fluctuation for over 600 cycles at a current density of 1 mA·cm
−2
. Our study not only provides a good CB@rGO host and pre-Lithiated CB@rGO composite anode electrode, but also brings a new strategy of designing 3D electrodes for those active materials suffering from severe volume expansion.
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