Supercurrent in the Presence of Direct Transmission and a Resonant Localized State.

We study the current-phase relation (CPR) of an InSb-Al nanowire Josephson junction in parallel magnetic fields up to 700 mT. At high magnetic fields and in narrow voltage intervals of a gate under the junction, the CPR exhibits π shifts. The supercurrent declines within these gate intervals and shows asymmetric gate voltage dependence above and below them. We detect these features sometimes also at zero magnetic field. The observed CPR properties are reproduced by a theoretical model of supercurrent transport via interference between direct transmission and a resonant localized state.

Gate-defined quantum point contacts in a germanium quantum well.

We report an experimental study of quantum point contacts defined in a high-quality strained germanium quantum well with layered electric gates. At a zero magnetic field, we observed quantized conductance plateaus in units of 2e2/h. Bias-spectroscopy measurements reveal that the energy spacing between successive one-dimensional subbands ranges from 1.5 to 5 meV as a consequence of the small effective mass of the holes and the narrow gate constrictions. At finite magnetic fields perpendicular to the device plane, the edges of the conductance plateaus get split due to the Zeeman effect and Landé g factors were estimated to be ∼6.6 for the holes in the germanium quantum well. We demonstrate that all quantum point contacts in the same device have comparable performances, indicating a reliable and reproducible device fabrication process. Thus, our work lays a foundation for investigating multiple forefronts of physics in germanium-based quantum devices that require quantum point contacts as building blocks.

Subgap spectroscopy along hybrid nanowires by nm-thick tunnel barriers.

Tunneling spectroscopy is widely used to examine the subgap spectra in semiconductor-superconductor nanostructures when searching for Majorana zero modes (MZMs). Typically, semiconductor sections controlled by local gates at the ends of hybrids serve as tunnel barriers. Besides detecting states only at the hybrid ends, such gate-defined tunnel probes can cause the formation of non-topological subgap states that mimic MZMs. Here, we develop an alternative type of tunnel probes to overcome these limitations. After the growth of an InSb-Al hybrid nanowire, a precisely controlled in-situ oxidation of the Al shell is performed to yield a nm-thick AlOx layer. In such thin isolating layer, tunnel probes can be arbitrarily defined at any position along the hybrid nanowire by shadow-wall angle-deposition of metallic leads. In this work, we make multiple tunnel probes along single nanowire hybrids and successfully identify Andreev bound states (ABSs) of various spatial extension residing along the hybrids.

Supercurrent, Multiple Andreev Reflections and Shapiro Steps in InAs Nanosheet Josephson Junctions.

We report an experimental study of proximity induced superconductivity in planar Josephson junction devices made from free-standing InAs nanosheets. The nanosheets are grown by molecular beam epitaxy, and the Josephson junction devices are fabricated by directly contacting the nanosheets with superconductor Al electrodes. The fabricated devices are explored by low-temperature carrier transport measurements. The measurements show that the devices exhibit a gate-tunable supercurrent, multiple Andreev reflections, and a good quality superconductor-semiconductor interface. The superconducting characteristics of the Josephson junctions are investigated at different magnetic fields and temperatures and are analyzed based on the Bardeen-Cooper-Schrieffer (BCS) theory. The measurements of the ac Josephson effect are also conducted under microwave radiations with different radiation powers and frequencies, and integer Shapiro steps are observed. Our work demonstrates that InAs nanosheet based hybrid devices are desired systems for investigating the forefront of physics, such as two-dimensional topological superconductivity.

The transcription factor HBP1 promotes ferroptosis in tumor cells by regulating the UHRF1-CDO1 axis.

The induction of ferroptosis in tumor cells is one of the most important mechanisms by which tumor progression can be inhibited; however, the specific regulatory mechanism underlying ferroptosis remains unclear. In this study, we found that transcription factor HBP1 has a novel function of reducing the antioxidant capacity of tumor cells. We investigated the important role of HBP1 in ferroptosis. HBP1 down-regulates the protein levels of UHRF1 by inhibiting the expression of the UHRF1 gene at the transcriptional level. Reduced levels of UHRF1 have been shown to regulate the ferroptosis-related gene CDO1 by epigenetic mechanisms, thus up-regulating the level of CDO1 and increasing the sensitivity of hepatocellular carcinoma and cervical cancer cells to ferroptosis. On this basis, we constructed metal-polyphenol-network coated HBP1 nanoparticles by combining biological and nanotechnological. MPN-HBP1 nanoparticles entered tumor cells efficiently and innocuously, induced ferroptosis, and inhibited the malignant proliferation of tumors by regulating the HBP1-UHRF1-CDO1 axis. This study provides a new perspective for further research on the regulatory mechanism underlying ferroptosis and its potential role in tumor therapy.

Electrostatic control of the proximity effect in the bulk of semiconductor-superconductor hybrids.

The proximity effect in semiconductor-superconductor nanowires is expected to generate an induced gap in the semiconductor. The magnitude of this induced gap, together with the semiconductor properties like spin-orbit coupling and g-factor, depends on the coupling between the materials. It is predicted that this coupling can be adjusted through the use of electric fields. We study this phenomenon in InSb/Al/Pt hybrids using nonlocal spectroscopy. We show that these hybrids can be tuned such that the semiconductor and superconductor are strongly coupled. In this case, the induced gap is similar to the superconducting gap in the Al/Pt shell and closes only at high magnetic fields. In contrast, the coupling can be suppressed which leads to a strong reduction of the induced gap and critical magnetic field. At the crossover between the strong-coupling and weak-coupling regimes, we observe the closing and reopening of the induced gap in the bulk of a nanowire. Contrary to expectations, it is not accompanied by the formation of zero-bias peaks in the local conductance spectra. As a result, this cannot be attributed conclusively to the anticipated topological phase transition and we discuss possible alternative explanations.

PD-L1: expression regulation.

Programmed death-ligand 1 (PD-L1), expressed on the surface of tumor cells, can bind to programmed cell death-1 (PD-1) on T cells. The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis. Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity, and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects; however, not all tumor patients benefit from these therapies. Therefore, study of the mechanisms regulating PD-L1 expression are imperative. In this review, we explore regulation of PD-L1 expression in the contexts of gene transcription, signaling pathways, histone modification and remodeling, microRNAs, long noncoding RNAs, and post-translational modification. Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized. Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.

Impact of Junction Length on Supercurrent Resilience against Magnetic Field in InSb-Al Nanowire Josephson Junctions.

Semiconducting nanowire Josephson junctions represent an attractive platform to investigate the anomalous Josephson effect and detect topological superconductivity. However, an external magnetic field generally suppresses the supercurrent through hybrid nanowire junctions and significantly limits the field range in which the supercurrent phenomena can be studied. In this work, we investigate the impact of the length of InSb-Al nanowire Josephson junctions on the supercurrent resilience against magnetic fields. We find that the critical parallel field of the supercurrent can be considerably enhanced by reducing the junction length. Particularly, in 30 nm long junctions supercurrent can persist up to 1.3 T parallel field─approaching the critical field of the superconducting film. Furthermore, we embed such short junctions into a superconducting loop and obtain the supercurrent interference at a parallel field of 1 T. Our findings are highly relevant for multiple experiments on hybrid nanowires requiring a magnetic-field-resilient supercurrent.

Realization of a minimal Kitaev chain in coupled quantum dots.

Majorana bound states constitute one of the simplest examples of emergent non-Abelian excitations in condensed matter physics. A toy model proposed by Kitaev shows that such states can arise at the ends of a spinless p-wave superconducting chain1. Practical proposals for its realization2,3 require coupling neighbouring quantum dots (QDs) in a chain through both electron tunnelling and crossed Andreev reflection4. Although both processes have been observed in semiconducting nanowires and carbon nanotubes5-8, crossed-Andreev interaction was neither easily tunable nor strong enough to induce coherent hybridization of dot states. Here we demonstrate the simultaneous presence of all necessary ingredients for an artificial Kitaev chain: two spin-polarized QDs in an InSb nanowire strongly coupled by both elastic co-tunnelling (ECT) and crossed Andreev reflection (CAR). We fine-tune this system to a sweet spot where a pair of poor man's Majorana states is predicted to appear. At this sweet spot, the transport characteristics satisfy the theoretical predictions for such a system, including pairwise correlation, zero charge and stability against local perturbations. Although the simple system presented here can be scaled to simulate a full Kitaev chain with an emergent topological order, it can also be used imminently to explore relevant physics related to non-Abelian anyons.

HBP1 inhibits the development of type 2 diabetes mellitus through transcriptional activation of the IGFBP1 gene.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is highly prevalent worldwide and characterized by glucose and lipid metabolism disorders. However, the pathogenic mechanisms have not been fully established. Here, we found that HMG-box transcription factor 1 (HBP1) is involved in T2DM and that its deficiency in mice aggravates the features of diabetes. In addition, we undertook screening by RNA sequencing and found that HBP1 activates the transcription of the insulin-like growth factor binding protein 1 (IGFBP1) gene. Moreover, Insulin and palmitic acid reduced HBP1 protein expression and inhibited its binding to the IGFBP1 promoter. Furthermore, HBP1 reduced the serum free insulin-like growth factor 1 (IGF-1) concentration through IGFBP1 and inhibited the PI3K/AKT signaling pathway. This forms an insulin/HBP1/IGFBP1 negative feedback regulatory loop to dynamically regulate blood glucose and insulin concentrations. These findings have elucidated a mechanism whereby HBP1 and its negative feedback regulatory loop influence the development of T2DM, thereby providing a new theoretical basis and potential therapeutic target for T2DM.

Charge detection of a quantum dot under different tunneling barrier symmetries and bias voltages.

We report the realization of a coupled quantum dot (QD) system containing two single QDs made in two adjacent InAs nanowires. One QD (sensor QD) was used as a charge sensor to detect the charge state transitions in the other QD (target QD). We investigated the effect of the tunneling barrier asymmetry of the target QD on the detection visibility of the charge state transitions in the target QD. The charge stability diagrams of the target QD under different configurations of barrier-gate voltages were simultaneously measured via the direct signals of electron transport through the target QD and via the detection signals of the charge state transitions in the target QD revealed by the sensor QD. We find that the complete Coulomb diamond boundaries of the target QD and the transport processes involving the excited states in the target QD can be observed in the transconductance signals of the sensor QD only when the tunneling barriers of the target QD are nearly symmetric. These observations were explained by analyzing the effect of the ratio of the two tunneling rates on the electron transport processes through the target QD. Our results imply that it is important to consider the symmetry of the tunnel couplings when constructing a charge sensor integrated QD device.

Methylation of HBP1 by PRMT1 promotes tumor progression by regulating actin cytoskeleton remodeling.

HBP1 is a sequence-specific transcription factor which generally considered as a crucial growth inhibitor. Posttranslational modification of HBP1 is vital for its function. In this study, we demonstrate that HBP1 is methylated at R378 by PRMT1, which decreases HBP1 protein stability by promoting its ubiquitination and proteasome-mediated degradation. PRMT1-mediated methylation of HBP1 alleviates the repressive effects of HBP1 on tumor metastasis and growth. GSN is identified as a novel target gene of HBP1. Methylation of HBP1 promotes actin cytoskeleton remodeling, glycolysis and tumor progression by downregulating GSN (a vital actin-binding protein) levels. The methylated HBP1-GSN axis is associated with the clinical outcomes of cancer patients. This investigation elucidates the mechanism of how methylated HBP1 facilitates actin cytoskeleton remodeling, thus attenuates its tumor-suppressive function and promotes tumor progression. Targeting methylated HBP1-GSN axis may provide a therapeutic strategy for cancer.

Spin-Mixing Enhanced Proximity Effect in Aluminum-Based Superconductor-Semiconductor Hybrids.

In superconducting quantum circuits, aluminum is one of the most widely used materials. It is currently also the superconductor of choice for the development of topological qubits. However, aluminum-based devices suffer from poor magnetic field compatibility. Herein, this limitation is resolved by showing that adatoms of heavy elements (e.g., platinum) increase the critical field of thin aluminum films by more than a factor of two. Using tunnel junctions, it is shown that the increased field resilience originates from spin-orbit scattering introduced by Pt. This property is exploited in the context of the superconducting proximity effect in semiconductor-superconductor hybrids, where it is shown that InSb nanowires strongly coupled to Al/Pt films can maintain superconductivity up to 7 T. The two-electron charging effect is shown to be robust against the presence of heavy adatoms. Additionally, non-local spectroscopy is used in a three-terminal geometry to probe the bulk of hybrid devices, showing that it remains free of sub-gap states. Finally, it is demonstrated that proximitized semiconductor states maintain their ability to Zeeman-split in an applied magnetic field. Combined with the chemical stability and well-known fabrication routes of aluminum, Al/Pt emerges as the natural successor to Al-based systems and is a compelling alternative to other superconductors, whenever high-field resilience is required.

Supercurrent parity meter in a nanowire Cooper pair transistor.

We study a Cooper pair transistor realized by two Josephson weak links that enclose a superconducting island in an InSb-Al hybrid nanowire. When the nanowire is subject to a magnetic field, isolated subgap levels arise in the superconducting island and, because of the Coulomb blockade, mediate a supercurrent by coherent cotunneling of Cooper pairs. We show that the supercurrent resulting from such cotunneling events exhibits, for low to moderate magnetic fields, a phase offset that discriminates even and odd charge ground states on the superconducting island. Notably, this phase offset persists when a subgap state approaches zero energy and, based on theoretical considerations, permits parity measurements of subgap states by supercurrent interferometry. Such supercurrent parity measurements could, in a series of experiments, provide an alternative approach for manipulating and protecting quantum information stored in the isolated subgap levels of superconducting islands.

GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells.

Golgi protein 73 (GP73) and alpha fetoprotein (AFP) serve as biomarkers for the diagnosis of hepatocellular carcinoma (HCC), and their serum levels correlate with patients' outcomes. However, the mechanisms underlying these correlations are unknown. Here we show that GP73 increased the secretion of AFP through direct binding to AFP, thereby promoting the proliferation and metastasis of HCC cells that expressed AFP and its receptor (AFPR). Extracellular GP73 contributed to the proliferation and metastasis of HCC cells independent of AFP and AFPR. Moreover, extracellular AFP and GP73 synergized to enhance the malignant phenotype of HCC cells. Furthermore, extracellular GP73 and AFP inhibited the antitumor effects of sorafenib and synergistically increased the drug resistance of HCC cells. These findings, which reveal the mechanism of GP73-mediated secretion of AFP and its effects on the malignant phenotype of HCC cells, provide a comprehensive theoretical basis for the diagnosis and treatment of HCC and identify potential drug targets.

HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression.

BACKGROUND: Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. METHODS: The expression of transcription factor HBP1 and AFP and clinical significance were further analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, Luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1-/- mice. RESULTS: The relative expressions of HBP1 and AFP correlated with survival and prognosis in hepatoma patients. HBP1 repressed the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promoted malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibited malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuated AFP effect on PTEN, MMP9 and caspase-3, thus inhibited proliferation and migration, and induced apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributed to hepatoma progression in mice. CONCLUSIONS: Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the diagnosis and treatment of hepatoma.

Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma.

BACKGROUND: Icaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway. METHODS: Real-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting. RESULTS: Our results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis. CONCLUSION: Our findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

A highly tunable quadruple quantum dot in a narrow bandgap semiconductor InAs nanowire.

Quantum dots (QDs) made from semiconductors are among the most promising platforms for the development of quantum computing and simulation chips, and they have the advantages of high density integration and compatibility with the standard semiconductor chip fabrication technology compared to other platforms. However, the development of a highly tunable semiconductor multiple QD system still remains a major challenge. Here, we demonstrate the realization of a highly tunable linear quadruple QD (QQD) in a narrow bandgap semiconductor InAs nanowire via a fine finger gate technique. The QQD is studied by electron transport measurements in the linear response regime. Characteristic two-dimensional charge stability diagrams containing four groups of resonant current lines of different slopes are obtained for the QQD. It is shown that these current lines arise from and can be individually assigned to resonant electron transport through the energy levels of different QDs. Benefitting from the excellent gate tunability, we also demonstrate the tuning of the QQD to regimes where the energy levels of two QDs, three QDs and all four QDs are energetically in resonance, respectively, with the Fermi level of the source and drain contacts. A capacitance network model is developed for the linear QQD and the simulated charge stability diagrams based on this model show good agreement with the experiments. Our work provides solid experimental evidence that narrow bandgap semiconductor nanowire multiple QDs could be used as a versatile platform to achieve integrated qubits for quantum computing and to perform quantum simulations of complex many-body systems.

A charge sensor integration to tunable double quantum dots on two neighboring InAs nanowires.

A single quantum dot serving as a charge sensor is integrated to scalable double quantum dots using local top finger-gate techniques on two neighboring pure-phase InAs nanowires. The single dot built on one nanowire capacitively couples one of the double dots constructed on another nanowire via a metal bridge gate. The charge occupation states of double quantum dots can be accurately monitored by the sensor even in a few-electron regime in which transport tunneling current through the double dots vanishes. In the tunneling spectroscopy of double dots, electron inter dot tunneling process is absent; however, it can be illustrated by the sensor in terms of a transconductance line between the two closest triple points. Thus, tunnel coupling strength between the double dots is quantitatively extracted from the detectable charge transition. The highly tunable multiple quantum dots with integrated charge sensors on InAs nanowires could be an essential building block for quantum information processing technology.

Measurements of anisotropic g-factors for electrons in InSb nanowire quantum dots.

We have measured the Zeeman splitting of quantum levels in few-electron quantum dots (QDs) formed in narrow bandgap InSb nanowires via the Schottky barriers at the contacts under application of different spatially orientated magnetic fields. The effective g-factor tensor extracted from the measurements is strongly anisotropic and level-dependent, which can be attributed to the presence of strong spin-orbit interaction (SOI) and asymmetric quantum confinement potentials in the QDs. We have demonstrated a successful determination of the principal values and the principal axis orientations of the g-factor tensors in an InSb nanowire QD by the measurements under rotations of a magnetic field in the three orthogonal planes. We also examine the magnetic field evolution of the excitation spectra in an InSb nanowire QD and extract a SOI strength of [Formula: see text] ∼ 180 µeV from an avoided level crossing between a ground state and its neighboring first excited state in the QD.