USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.

Ferroptosis is an iron-dependent type of regulated cell death resulting from extensive lipid peroxidation and plays a critical role in various physiological and pathological processes. However, the regulatory mechanisms for ferroptosis sensitivity remain incompletely understood. Here, we report that homozygous deletion of Usp8 (ubiquitin-specific protease 8) in intestinal epithelial cells (IECs) leads to architectural changes in the colonic epithelium and shortens mouse lifespan accompanied by increased IEC death and signs of lipid peroxidation. However, mice with heterozygous deletion of Usp8 in IECs display normal phenotype and become resistant to azoxymethane/dextran sodium sulfate-induced colorectal tumorigenesis. Mechanistically, USP8 interacts with and deubiquitinates glutathione peroxidase 4 (GPX4), leading to GPX4 stabilization. Thus, USP8 inhibition destabilizes GPX4 and sensitizes cancer cells to ferroptosis in vitro. Notably, USP8 inhibition in combination with ferroptosis inducers retards tumor growth and enhances CD8+ T cell infiltration, which potentiates tumor response to anti-PD-1 immunotherapy in vivo. These findings uncover that USP8 counteracts ferroptosis by stabilizing GPX4 and highlight targeting USP8 as a potential therapeutic strategy to boost ferroptosis for enhancing cancer immunotherapy.

Highly Tunable 2D Silicon Quantum Dot Array with Coupling beyond Nearest Neighbors.

Scaling up quantum dots to two-dimensional (2D) arrays is a crucial step for advancing semiconductor quantum computation. However, maintaining excellent tunability of quantum dot parameters, including both nearest-neighbor and next-nearest-neighbor couplings, during 2D scaling is challenging, particularly for silicon quantum dots due to their relatively small size. Here, we present a highly controllable and interconnected 2D quantum dot array in planar silicon, demonstrating independent control over electron fillings and the tunnel couplings of nearest-neighbor dots. More importantly, we also demonstrate the wide tuning of tunnel couplings between next-nearest-neighbor dots, which play a crucial role in 2D quantum dot arrays. This excellent tunability enables us to alter the coupling configuration of the array as needed. These results open up the possibility of utilizing silicon quantum dot arrays as versatile platforms for quantum computing and quantum simulation.

Quantum Interference and Coherent Population Trapping in a Double Quantum Dot.

Quantum interference is a natural consequence of wave-particle duality in quantum mechanics, and is widely observed at the atomic scale. One interesting manifestation of quantum interference is coherent population trapping (CPT), first proposed in three-level driven atomic systems and observed in quantum optical experiments. Here, we demonstrate CPT in a gate-defined semiconductor double quantum dot (DQD), with some unique twists as compared to the atomic systems. Specifically, we observe CPT in both driven and nondriven situations. We further show that CPT in a driven DQD could be used to generate adiabatic state transfer. Moreover, our experiment reveals a nontrivial modulation to the CPT caused by the longitudinal driving field, yielding an odd-even effect and a tunable CPT. Our results broaden the field of CPT, and open up the possibility of quantum simulation and quantum computation based on adiabatic passage in quantum dot systems.

A machine learning-based workflow for predicting transplant outcomes in patients with sickle cell disease.

Allogeneic haematopoietic cell transplantation (HCT) with HLA-matched sibling donor remains the most established curative therapeutic option for patients with sickle cell disease (SCD). However, it is not without risks, highlighting the need for a risk stratification system. Utilizing a machine learning (ML) approach that combines clinical and imaging variables, we identified red cell distribution width and renal organ damage as important risk factors for patients undergoing HCT. This ML-based algorithm, similar to an approach previously reported for predicting mortality in patients with SCD, should be applicable to risk factor discovery in similar studies.

Magnetic detection under high pressures using designed silicon vacancy centres in silicon carbide.

Pressure-induced magnetic phase transitions are attracting interest as a means to detect superconducting behaviour at high pressures in diamond anvil cells, but determining the local magnetic properties of samples is a challenge due to the small volumes of sample chambers. Optically detected magnetic resonance of nitrogen vacancy centres in diamond has recently been used for the in situ detection of pressure-induced phase transitions. However, owing to their four orientation axes and temperature-dependent zero-field splitting, interpreting these optically detected magnetic resonance spectra remains challenging. Here we study the optical and spin properties of implanted silicon vacancy defects in 4H-silicon carbide that exhibit single-axis and temperature-independent zero-field splitting. Using this technique, we observe the magnetic phase transition of Nd2Fe14B at about 7 GPa and map the critical temperature-pressure phase diagram of the superconductor YBa2Cu3O6.6. These results highlight the potential of silicon vacancy-based quantum sensors for in situ magnetic detection at high pressures.

Ultrafast and Electrically Tunable Rabi Frequency in a Germanium Hut Wire Hole Spin Qubit.

Hole spin qubits based on germanium (Ge) have strong tunable spin-orbit interaction (SOI) and ultrafast qubit operation speed. Here we report that the Rabi frequency (fRabi) of a hole spin qubit in a Ge hut wire (HW) double quantum dot (DQD) is electrically tuned through the detuning energy (ϵ) and middle gate voltage (VM). fRabi gradually decreases with increasing ϵ; on the contrary, fRabi is positively correlated with VM. We attribute our results to the change of electric field on SOI and the contribution of the excited state in quantum dots to fRabi. We further demonstrate an ultrafast fRabi exceeding 1.2 GHz, which indicates the strong SOI in our device. The discovery of an ultrafast and electrically tunable fRabi in a hole spin qubit has potential applications in semiconductor quantum computing.

Collective Microwave Response for Multiple Gate-Defined Double Quantum Dots.

We fabricate and characterize a hybrid quantum device that consists of five gate-defined double quantum dots (DQDs) and a high-impedance NbTiN transmission resonator. The controllable interactions between DQDs and the resonator are spectroscopically explored by measuring the microwave transmission through the resonator in the detuning parameter space. Utilizing the high tunability of the system parameters and the high cooperativity (Ctotal > 17.6) interaction between the qubit ensemble and the resonator, we tune the charge-photon coupling and observe the collective microwave response changing from linear to nonlinear. Our results present the maximum number of DQDs coupled to a resonator and manifest a potential platform for scaling up qubits and studying collective quantum effects in semiconductor-superconductor hybrid cavity quantum electrodynamics systems.

The AtMINPP Gene, Encoding a Multiple Inositol Polyphosphate Phosphatase, Coordinates a Novel Crosstalk between Phytic Acid Metabolism and Ethylene Signal Transduction in Leaf Senescence.

Plant senescence is a highly coordinated process that is intricately regulated by numerous endogenous and environmental signals. The involvement of phytic acid in various cell signaling and plant processes has been recognized, but the specific roles of phytic acid metabolism in Arabidopsis leaf senescence remain unclear. Here, we demonstrate that in Arabidopsis thaliana the multiple inositol phosphate phosphatase (AtMINPP) gene, encoding an enzyme with phytase activity, plays a crucial role in regulating leaf senescence by coordinating the ethylene signal transduction pathway. Through overexpressing AtMINPP (AtMINPP-OE), we observed early leaf senescence and reduced chlorophyll contents. Conversely, a loss-of-function heterozygous mutant (atminpp/+) exhibited the opposite phenotype. Correspondingly, the expression of senescence-associated genes (SAGs) was significantly upregulated in AtMINPP-OE but markedly decreased in atminpp/+. Yeast one-hybrid and chromatin immunoprecipitation assays indicated that the EIN3 transcription factor directly binds to the promoter of AtMINPP. Genetic analysis further revealed that AtMINPP-OE could accelerate the senescence of ein3-1eil1-3 mutants. These findings elucidate the mechanism by which AtMINPP regulates ethylene-induced leaf senescence in Arabidopsis, providing insights into the genetic manipulation of leaf senescence and plant growth.

All layers patterned conical nanostructured thin-film silicon solar cells for light-trapping efficiency improvement.

Thin-film silicon solar cells (TSSC) has received great attention due to its advantages of low cost and eco-friendly. However, traditional single-layer patterned solar cells (SPSC) still fall short in light-trapping efficiency. This article presents an all layers patterned (ALP) conical nanostructured TSSC to enhance the low absorption caused by the thin absorption layers. The Finite-Difference Time-Domain result shows that a photocurrent density up to 41.27 mA/cm2 can be obtained for the structure, which is 31.39% higher than that of the SPSC. An electrical optimization simulation of doping concentration was carried out on the parameters of the optically optimal structure of the model. The power conversion efficiency is 17.15%, which is 1.72 times higher than that of the planar structure. These results demonstrate a success for the potential and prospect of the fully patterned nanostructures in thin-film photovoltaic devices.

Probing Two Driven Double Quantum Dots Strongly Coupled to a Cavity.

We experimentally and theoretically study a driven hybrid circuit quantum electrodynamics (cQED) system beyond the dispersive coupling regime. Treating the cavity as part of the driven system, we develop a theory applicable to such strongly coupled and to multiqubit systems. The fringes measured for a single driven double quantum dot (DQD)-cavity setting and the enlarged splittings of the hybrid Floquet states in the presence of a second DQD are well reproduced with our model. This opens a path to study Floquet states of multiqubit systems with arbitrarily strong coupling and reveals a new perspective for understanding strongly driven hybrid systems.

Estimated sdLDL-C for predicting high-risk coronary plaque features in psoriasis: a prospective observational study.

BACKGROUND: Psoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive. METHODS: A recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C. RESULTS: Estimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (ß = 0.37; P = 0.050) and LDL-C adjustment for FFB (ß = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C. CONCLUSIONS: Estimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifiers: NCT01778569.

Coherent phonon dynamics in spatially separated graphene mechanical resonators.

Vibrational modes in mechanical resonators provide a promising candidate to interface and manipulate classical and quantum information. The observation of coherent dynamics between distant mechanical resonators can be a key step toward scalable phonon-based applications. Here we report tunable coherent phonon dynamics with an architecture comprising three graphene mechanical resonators coupled in series, where all resonators can be manipulated by electrical signals on control gates. We demonstrate coherent Rabi oscillations between spatially separated resonators indirectly coupled via an intermediate resonator serving as a phonon cavity. The Rabi frequency fits well with the microwave burst power on the control gate. We also observe Ramsey interference, where the oscillation frequency corresponds to the indirect coupling strength between these resonators. Such coherent processes indicate that information encoded in vibrational modes can be transferred and stored between spatially separated resonators, which can open the venue of on-demand phonon-based information processing.

Coherent Control and Magnetic Detection of Divacancy Spins in Silicon Carbide at High Pressures.

Spin defects in silicon carbide appear to be a promising tool for various quantum technologies, especially for quantum sensing. However, this technique has been used only at ambient pressure until now. Here, by combining this technique with diamond anvil cell, we systematically study the optical and spin properties of divacancy defects created at the surface of SiC at pressures up to 40 GPa. The zero-field-splitting of the divacancy spins increases linearly with pressure with a slope of 25.1 MHz/GPa, which is almost two-times larger than that of nitrogen-vacancy centers in diamond. The corresponding pressure sensing sensitivity is about 0.28 MPa/Hz-1/2. The coherent control of divacancy demonstrates that coherence time decreases as pressure increases. Based on these, the pressure-induced magnetic phase transition of Nd2Fe14B sample at high pressures was detected. These experiments pave the way to use divacancy in quantum technologies such as pressure sensing and magnetic detection at high pressures.

YUCCA2 (YUC2)-Mediated 3-Indoleacetic Acid (IAA) Biosynthesis Regulates Chloroplast RNA Editing by Relieving the Auxin Response Factor 1 (ARF1)-Dependent Inhibition of Editing Factors in Arabidopsis thaliana.

Although recent research progress on the abundant C-to-U RNA editing events in plant chloroplasts and mitochondria has uncovered many recognition factors and their molecular mechanisms, the intrinsic regulation of RNA editing within plants remains largely unknown. This study aimed to establish a regulatory relationship in Arabidopsis between the plant hormone auxin and chloroplast RNA editing. We first analyzed auxin response elements (AuxREs) present within promoters of chloroplast editing factors reported to date. We found that each has more than one AuxRE, suggesting a potential regulatory role of auxin in their expression. Further investigation unveiled that the depletion of auxin synthesis gene YUC2 reduces the expression of several editing factors. However, in yuc2 mutants, only the expression of CRR4, DYW1, ISE2, and ECD1 editing factors and the editing efficiency of their corresponding editing sites, ndhD-2 and rps14-149, were simultaneously suppressed. In addition, exogenous IAA and the overexpression of YUC2 enhanced the expression of these editing factors and the editing efficiency at the ndhD-2 and rps14-149 sites. These results suggested a direct effect of auxin upon the editing of the ndhD-2 and rps14-149 sites through the modulation of the expression of the editing factors. We further demonstrated that ARF1, a downstream transcription factor in the auxin-signaling pathway, could directly bind to and inactivate the promoters of CRR4, DYW1, and ISE2 in a dual-luciferase reporter system, thereby inhibiting their expression. Moreover, the overexpression of ARF1 in Arabidopsis significantly reduced the expression of the three editing factors and the editing efficiency at the ndhD-2 and rps14-149 sites. These data suggest that YUC2-mediated auxin biosynthesis governs the RNA-editing process through the ARF1-dependent signal transduction pathway.

Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development.

Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14-SMXL7 and AtD14-MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants.

Tunable and anisotropic perfect absorber using graphene-black phosphorus nanoblock.

Two-dimensional (2D) materials, which have attracted attention due to intriguing optical properties, form a promising building block in optical and photonic devices. This paper numerically investigates a tunable and anisotropic perfect absorber in a graphene-black phosphorus (BP) nanoblock array structure. The suggested structure exhibits polarization-dependent anisotropic absorption in the mid-infrared, with maximum absorption of 99.73% for x-polarization and 53.47% for y-polarization, as determined by finite-difference time-domain FDTD analysis. Moreover, geometrical parameters and graphene and BP doping amounts are possibly employed to tailor the absorption spectra of the structures. Hence, our results have the potential in the design of polarization-selective and tunable high-performance devices in the mid-infrared, such as polarizers, modulators, and photodetectors.

Individually tunable array reflector for amplitude and phase modulation.

Based on graphene's phase modulation property and vanadium dioxide's amplitude modulation property, we developed an array reflector for terahertz frequencies that is individually adjustable. Starting with a theoretical analysis, we look into the effects of voltage on the Fermi level of graphene and temperature on the conductivity of vanadium dioxide, analyze the beam focusing characteristics, and finally link the controllable quantities with the reflected beam characteristics to independently regulate each cell in the array. The simulation findings demonstrate that the suggested array structure can precisely manage the focus point's position, intensity, and scattering degree and that, with phase compensation, it can control the wide-angle incident light. The array structure offers a novel concept for adjustable devices and focusing lenses, which has excellent potential for study and application.

Anisotropic g-Factor and Spin-Orbit Field in a Germanium Hut Wire Double Quantum Dot.

Holes in nanowires have drawn significant attention in recent years because of the strong spin-orbit interaction, which plays an important role in constructing Majorana zero modes and manipulating spin-orbit qubits. Here, from the strongly anisotropic leakage current in the spin blockade regime for a double dot, we extract the full g-tensor and find that the spin-orbit field is in plane with an azimuthal angle of 59° to the axis of the nanowire. The direction of the spin-orbit field indicates a strong spin-orbit interaction along the nanowire, which may have originated from the interface inversion asymmetry in Ge hut wires. We also demonstrate two different spin relaxation mechanisms for the holes in the Ge hut wire double dot: spin-flip co-tunneling to the leads, and spin-orbit interaction within the double dot. These results help establish feasibility of a Ge-based quantum processor.

Research on RNA secondary structure predicting via bidirectional recurrent neural network.

BACKGROUND: RNA secondary structure prediction is an important research content in the field of biological information. Predicting RNA secondary structure with pseudoknots has been proved to be an NP-hard problem. Traditional machine learning methods can not effectively apply protein sequence information with different sequence lengths to the prediction process due to the constraint of the self model when predicting the RNA secondary structure. In addition, there is a large difference between the number of paired bases and the number of unpaired bases in the RNA sequences, which means the problem of positive and negative sample imbalance is easy to make the model fall into a local optimum. To solve the above problems, this paper proposes a variable-length dynamic bidirectional Gated Recurrent Unit(VLDB GRU) model. The model can accept sequences with different lengths through the introduction of flag vector. The model can also make full use of the base information before and after the predicted base and can avoid losing part of the information due to truncation. Introducing a weight vector to predict the RNA training set by dynamically adjusting each base loss function solves the problem of balanced sample imbalance. RESULTS: The algorithm proposed in this paper is compared with the existing algorithms on five representative subsets of the data set RNA STRAND. The experimental results show that the accuracy and Matthews correlation coefficient of the method are improved by 4.7% and 11.4%, respectively. CONCLUSIONS: The flag vector introduced allows the model to effectively use the information before and after the protein sequence; the introduced weight vector solves the problem of unbalanced sample balance. Compared with other algorithms, the LVDB GRU algorithm proposed in this paper has the best detection results.

DOC-2/DAB2 interactive protein destabilizes c-Myc to impair the growth and self-renewal of colon tumor-repopulating cells.

Colorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell-like colon tumor-repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c-Myc is essential for maintaining cancer stem-like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c-Myc protein supported formation and growth of TRC spheroids. The tumor suppressor DOC-2/DAB2 interactive protein (DAB2IP) suppressed c-Myc expression to inhibit TRC expansion and self-renewal. Particularly, DAB2IP disrupted c-Myc stability through glycogen synthase kinase 3ß/protein phosphatase 2A-B56α-mediated phosphorylation and dephosphorylation cascade on c-Myc protein, leading to its eventual degradation through the ubiquitin-proteasome pathway. The expression of DAB2IP was negatively correlated with c-Myc in CRC specimens. Overall, our results improved mechanistic insight into how DAB2IP suppressed TRC growth and self-renewal.