Naringenin enhances the efficacy of ferroptosis inducers by attenuating aerobic glycolysis by activating the AMPK-PGC1α signalling axis in liver cancer.

Liver cancer is a heterogeneous disease characterized by poor responses to standard therapies and therefore unfavourable clinical outcomes. Understanding the characteristics of liver cancer and developing novel therapeutic strategies are imperative. Ferroptosis, a type of programmed cell death induced by lipid peroxidation, has emerged as a potential target for treatment. Naringenin, a natural compound that modulates lipid metabolism by targeting AMPK, shows promise in enhancing the efficacy of ferroptosis inducers. In this study, we utilized liver cancer cell lines and xenograft mice to explore the synergistic effects of naringenin in combination with ferroptosis inducers, examining both phenotypic outcomes and molecular mechanisms. Our study results indicate that the use of naringenin at non-toxic doses to hepatocytes can significantly enhance the anticancer effects of ferroptosis inducers (erastin, RSL3, and sorafenib). The combination index method confirmed a synergistic effect between naringenin and ferroptosis inducers. In comparison to naringenin or ferroptosis inducers alone, the combined therapy caused more robust lipid peroxidation and hence more severe ferroptotic damage to cancer cells. The inhibition of aerobic glycolysis mediated by the AMPK-PGC1α signalling axis is the key to naringenin's effect on reducing ferroptosis resistance in liver cancer, and the synergistic cytotoxic effect of naringenin and ferroptosis inducers on cancer cells was reversed after pretreatment with an AMPK inhibitor or a PGC1α inhibitor. Taken together, these findings suggest that naringenin could boost cancer cell sensitivity to ferroptosis inducers, which has potential clinical translational value.

Extreme Thermal Insulation and Tradeoff of Thermal Transport Mechanisms between Graphene and WS2 Monolayers.

Controlling and understanding the heat flow at a nanometer scale are challenging, but important for fundamental science and applications. Two-dimensional (2D) layered materials provide perhaps the ultimate solution for meeting these challenges. While there have been reports of low thermal conductivities (several mW m-1 K-1) across the 2D heterostructures, phonon-dominant thermal transport remains strong due to the nearly-ideal contact between the layers. Here, this work experimentally explores the heat transport mechanisms by increasing the interlayer distance from perfect contact to a few nanometers and demonstrates that the phonon-dominated thermal conductivity across the WS2/graphene interface decreases further with the increasing interlayer distance until the air-dominated thermal conductivity increases again. This work finds that the resulting tradeoff of the two heat conduction mechanisms leads to the existence of a minimum thermal conductivity at 2.11 nm of 1.41 × 10-5 W m-1 K-1, which is two thousandths of the smallest value reported previously. This work provides an effective methodology for engineering thermal insulation structures and understanding heat transport at the ultimate small scales.

Large-Scale, High-Yield Laser Fabrication of Bright and Pure Single-Photon Emitters at Room Temperature in Hexagonal Boron Nitride.

Single-photon emitters (SPEs) play an important role in many optical quantum technologies. However, an efficient large-scale approach to the generation of high-quality SPE arrays remains an elusive goal at room temperature. Here, we demonstrate a scalable method of generating SPE arrays in hexagonal boron nitride (hBN) with high yield, brightness, and purity using single-pulse irradiation by a femtosecond laser. Our use of a single pulse per defect pattern minimized heat-related damages and improved the purity of SPEs compared with the previous laser-based approaches. Under the optimized fabrication and post-treatment conditions, SPE arrays were successfully generated from the 3.0 µm defect patterns with 43% yield, the highest among the 2D-based top-down approaches. Importantly, we found that 100% of the bright defect patterns are SPEs with g2(0) < 0.5 under such conditions, with the lowest g2(0) = 0.06 ± 0.03. Our SPEs also exhibit the highest brightness with the saturation SPE rate at 7.15 million counts per second. We believe that our overall high-quality and large-scale approach will help a wide range of applications of SPEs in on-chip quantum technologies.

Injection-free multiwavelength electroluminescence devices based on monolayer semiconductors driven by an alternating field.

Two-dimensional (2D) semiconductors have emerged as promising candidates for various optoelectronic devices especially electroluminescent (EL) devices. However, progress has been hampered by many challenges including metal contacts and injection, transport, and confinement of carriers due to small sizes of materials and the lack of proper double heterostructures. Here, we propose and demonstrate an alternative approach to conventional current injection devices. We take advantage of large exciton binding energies in 2D materials using impact generation of excitons through an alternating electric field, without requiring metal contacts to 2D materials. The conversion efficiency, defined as the ratio of the emitted photons to the preexisting carriers, can reach 16% at room temperature. In addition, we demonstrate the first multiwavelength 2D EL device, simultaneously operating at three wavelengths from red to near-infrared. Our approach provides an alternative to conventional current-based devices and could unleash the great potential of 2D materials for EL devices.

Nonvolatile electrical switching of optical and valleytronic properties of interlayer excitons.

Long-lived interlayer excitons (IXs) in van der Waals heterostructures (HSs) stacked by monolayer transition metal dichalcogenides (TMDs) carry valley-polarized information and thus could find promising applications in valleytronic devices. Current manipulation approaches for valley polarization of IXs are mainly limited in electrical field/doping, magnetic field or twist-angle engineering. Here, we demonstrate an electrochemical-doping method, which is efficient, in-situ and nonvolatile. We find the emission characteristics of IXs in WS2/WSe2 HSs exhibit a large excitonic/valley-polarized hysteresis upon cyclic-voltage sweeping, which is ascribed to the chemical-doping of O2/H2O redox couple trapped between WSe2 and substrate. Taking advantage of the large hysteresis, a nonvolatile valley-addressable memory is successfully demonstrated. The valley-polarized information can be non-volatilely switched by electrical gating with retention time exceeding 60 min. These findings open up an avenue for nonvolatile valley-addressable memory and could stimulate more investigations on valleytronic devices.

Diclofenac impairs the proliferation and glucose metabolism of triple-negative breast cancer cells by targeting the c-Myc pathway.

Triple-negative breast cancer (TNBC) cells obtain energy mainly through aerobic glycolysis, and their glycolytic rate is significantly higher compared with that of non-TNBC cells. Glucose transporter 1 (GLUT1) is a transmembrane transporter necessary for the entry of glucose into tumor cells, hexokinase (HK) is a key enzyme in the glycolytic pathway, and both are targets of the transcription factor c-Myc. c-Myc can promote aerobic glycolysis by upregulating GLUT1 expression and enhancing HK activity. c-Myc and GLUT1 are highly expressed in TNBC. The non-steroidal anti-inflammatory drug diclofenac can inhibit glycolysis in melanoma cells and thereby promote apoptosis by downregulating c-Myc and GLUT1. To explore the effect of diclofenac on the energy metabolism of TNBC cells and determine the underlying mechanism, a comparative study in two TNBC cell lines (MDA-MB-231 and HCC1937) and one non-TNBC cell line (MCF-7) was conducted. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) and flow cytometric assays; GLUT1 and c-Myc expression was measured by western blotting. Diclofenac significantly inhibited cell proliferation, downregulated GLUT1 and c-Myc expression, and decreased HK activity in TNBC cells compared with non-TNBC cells. In conclusion, the studies suggested that diclofenac inhibited cell glycolysis and suppressed TNBC cell growth by decreasing GLUT1 protein expression and HK activity through the c-Myc pathway.

Room-Temperature Exciton-Based Optoelectronic Switch.

Excitons, bound pairs of electrons and holes, could act as an intermediary between electronic signal processing and optical transmission, thus speeding up the interconnection of photoelectric communication. However, up to date, exciton-based logic devices such as switches that work at room temperature are still lacking. This work presents a prototype of a room-temperature optoelectronic switch based on excitons in WSe2 monolayer. The emission intensity of WSe2 stacked on Au and SiO2 substrates exhibits completely opposite behaviors upon applying gate voltages. Such observation can be ascribed to different doping behaviors of WSe2 caused by charge-transfer and chemical-doping effect at WSe2 /Au and WSe2 /SiO2 interfaces, respectively, together with the charge-drift effect. These interesting features can be utilized for optoelectronic switching, confirmed by the cyclic PL switching test for a long time exceeding 4000 s. This study offers a universal and reliable approach for the fabrication of exciton-based optoelectronic switches, which would be essential in integrated nanophotonics.

Excitonic complexes and optical gain in two-dimensional molybdenum ditelluride well below the Mott transition.

Semiconductors that can provide optical gain at extremely low carrier density levels are critically important for applications such as energy efficient nanolasers. However, all current semiconductor lasers are based on traditional semiconductor materials that require extremely high density levels above the so-called Mott transition to realize optical gain. The new emerging 2D materials provide unprecedented opportunities for studying new excitonic physics and exploring new optical gain mechanisms at much lower density levels due to the strong Coulomb interaction and co-existence and mutual conversion of excitonic complexes. Here, we report a new gain mechanism involving charged excitons or trions in electrically gated 2D molybdenum ditelluride well below the Mott density. Our combined experimental and modelling study not only reveals the complex interplay of excitonic complexes well below the Mott transition but also establishes 2D materials as a new class of gain materials at densities 4-5 orders of magnitude lower than those of conventional semiconductors and provides a foundation for lasing at ultralow injection levels for future energy efficient photonic devices. Additionally, our study could help reconcile recent conflicting results on 2D materials: While 2D material-based lasers have been demonstrated at extremely low densities with spectral features dominated by various excitonic complexes, optical gain was only observed in experiments at densities several orders of magnitude higher, beyond the Mott density. We believe that our results could lead to more systematic studies on the relationship between the mutual conversion of excitonic species and the existence of optical gain well below the Mott transition.

Room-temperature continuous-wave lasing from monolayer molybdenum ditelluride integrated with a silicon nanobeam cavity.

Monolayer transition-metal dichalcogenides (TMDs) have the potential to become efficient optical-gain materials for low-energy-consumption nanolasers with the smallest gain media because of strong excitonic emission. However, until now TMD-based lasing has been realized only at low temperatures. Here we demonstrate for the first time a room-temperature laser operation in the infrared region from a monolayer of molybdenum ditelluride on a silicon photonic-crystal cavity. The observation is enabled by the unique combination of a TMD monolayer with an emission wavelength transparent to silicon, and a high-Q cavity of the silicon nanobeam. The laser is pumped by a continuous-wave excitation, with a threshold density of 6.6 W cm-2. Its linewidth is as narrow as 0.202 nm with a corresponding Q of 5,603, the largest value reported for a TMD laser. This demonstration establishes TMDs as practical materials for integrated TMD-silicon nanolasers suitable for silicon-based nanophotonic applications in silicon-transparent wavelengths.

Strong Optomechanical Coupling in Nanobeam Cavities based on Hetero Optomechanical Crystals.

Nanobeam cavities based on hetero optomechanical crystals are proposed. With optical and mechanical modes separately confined by two types of periodic structures, the mechanical frequency is designed as high as 5.88 GHz. Due to the optical field and the strain field concentrated in the optomechanical cavity and resembling each other with an enhanced overlap, a high optomechanical coupling rate of 1.31 MHz is predicted.