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Single cell proteomic analysis defines discrete neutrophil functional states in human glioblastoma
Abstract Neutrophils are vital innate immune cells shown to infiltrate glioblastomas, however we currently lack the molecular understanding of their functional states within the tumour niche. Given that neutrophils are known to display a prominent discordance between mRNA and protein abundance, we developed ultra-sensitive mini-bulk and single cell proteomic (SCP) workflows to study the heterogeneity of peripheral blood and tumour associated neutrophils (TAN) from patients with glioblastoma. Mini-bulk analysis enabled a deeper protein coverage of circulating immature, mature and TAN populations, defining signatures of maturity and demonstrating that TANs resemble mature circulating neutrophils. Analysis of the SCP data results in the detection of >1100 proteins from a single TAN providing a detailed characterization of neutrophil subsets in glioblastoma. Our approach shows evidence of pathogenic and anti-tumorigenic clusters and discovers cell states invisible to scRNAseq, opening new opportunities to selectively target pro-tumoural neutrophil states.
Xiao‐Hui Yang
Dynamic correlation between surface states and exciton in perovskite nanocrystals growth and ligand binding
Colloidal lead halide perovskite (LHP) nanocrystals have attracted considerable interest in optoelectronics due to their exceptional photoelectric properties, yet quantifying the effect of nanocrystal surface states on exciton state alterations remains elusive, hindering understanding and modulation of exciton behavior. Here, we present a room-temperature synthesis strategy that decouples the supply pathways of ionized cesium and coordinated lead, enabling controlled nanocrystal growth over ∼20 min. Employing this methodology, we develop an in situ absorption-emission spectroscopy system to unveil dynamic association between nanocrystal growth kinetics and excitonic energy states, establishing a quantitative model for exciton physical characteristics. Further leveraging this dynamic correlation model, we probe the physical origin of the anomalous blue shifted absorption/emission spectra induced by benzenesulfonamide ligands. Our analysis reveals that ligand-mediated reduction of exciton binding energy constitutes the primary physical mechanism underlying the blue shifts. Urbach tail analysis confirms band edge disorder as the underlying mechanism. In situ spectroscopic monitoring and exciton state quantification enable the study of the dynamic photophysical properties of LHP nanocrystals.
Author Correction: PPIA dictates NRF2 stability to promote lung cancer progression
Persistent incommensurate charge density wave in chalcogen-disordered 1 <i>T</i> -TaSeTe
Charge density waves (CDWs) are a canonical interaction-driven electronic phenomenon with potential technological applications, such as collective electronic switching and local information storage. Here, we investigate the properties of the CDW in the mixed-chalcogen compound 1T-TaSeTe using bulk- and surface-sensitive diffraction and spectroscopy techniques and transport measurements. Compared to the pristine parent compound 1T-TaSe2, we find that the incommensurate CDW appears to remain incommensurate down to low temperatures. The CDW-induced gapping of the Fermi surface is pronounced and may explain the observed semiconductor-like electrical resistivity behavior in combination with chalcogen disorder. Our results demonstrate that disordered chalcogen substitution doping can modify, yet preserve, the characteristic emergent electronic properties of a transition metal dichalcogenide.
PD-1/ PD-L1 bispecific antibody IBI318 combined with lenvatinib in advanced non-small cell lung cancer with acquired resistance to immune checkpoint inhibitors: a phase II trial
High-performance long-wavelength infrared photodetector based on M-structure InAs/GaSb type-II superlattices
A high-performance long-wavelength infrared photodetector based on M-structure type-II superlattices was developed by optimizing the device structure and operating conditions. The detector exhibits a spectral response range of 3–12.5 μm, with a peak response of 4.73 A/W observed at 5.2 μm and 3.06 A/W at 8.1 μm. The quantum efficiency at 8 μm reaches approximately 50%. Notably, the response remains relatively constant under no bias or reverse bias. At an applied bias voltage of 10 mV, the detector's specific detectivity reached 3.62 × 1010 and 3.63 × 1010 cm·Hz0.5/W at 8 and 10 μm, respectively, demonstrating excellent detection capability in the long-wavelength range. Furthermore, D* remains above 1 × 1010 cm·Hz0.5/W for a bias voltage below 50 mV, demonstrating the detector's stability under low-bias conditions.
Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma
Abstract Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screen, we identify that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy-induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, results in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings demonstrate a role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.
A kind of carbon-based composites with both high heat conductivity and absorption capacity
With the rapid increase in power density of electronics, the demands for high-performance thermal management materials have become more and more urgent. The good performance of both heat transfer and adsorption is simultaneously required to control the temperature of electronic at a reasonable level. Herein, intermediate phase asphalt-based short carbon fibers (SCFs) and paraffin (Pa) are incorporated into polyolefin elastomer (POE) matrix to construct highly thermally conductive phase change composites (PCCs). Through a series of steps such as melt blending, hot-pressing, and cutting, the obtained L1-30 wt. % (600 μm)/P1E1 PCC exhibits a through-plane thermal conductivity of 10.43 W m−1 K−1 and good heat absorption capacity. Moreover, the molecular network of POE matrix and SCFs skeleton are proved to be effectively prevent the phase change materials from leakage. In a thermal management test, the prepared PCC presents a temperature decline of 17.8 °C than that of the naked heater. This work gives a perspective to fabricate thermally conductive PCCs with oriented fillers as well as to find potential application in the thermal management of electronics.
Single-neuron correlates of visual consciousness in human lateral occipital complex
Abstract Conscious perception, a critical aspect of human cognition, is assumed to emerge from a complex network of interacting brain regions that transmit information via feedforward and recurrent pathways. This study presents single- and multiunit recordings from the human lateral occipital complex (LO), a key region for shape and object recognition, during three distinct perceptual paradigms: backward masking, flash suppression and binocular rivalry. Stimulus awareness increased decoding accuracy and decoders assigned higher probabilities to the consciously perceived stimulus during periods of dichoptic stimulus presentation. These findings highlight the intricate neural mechanisms underlying visual awareness and show that LO responses predominantly align with subjective phenomenology, offering new insights into the neural correlates of visual consciousness.
The study of thermal fluctuations in microwave and mechanical resonators
We report high-resolution measurements of thermal fluctuations in microwave and mechanical resonators using a dual-channel readout system. The latter comprises a low-noise amplifier, an I/Q-mixer, and a cross-correlator. We discovered that, under certain conditions, the intrinsic fluctuations of the low-noise amplifier, which are common to both channels of the readout system, are averaged out when computing the voltage noise cross-spectrum between the mixer's outputs. The suppression of the amplifier's technical fluctuations significantly improves the contrast of the thermal noise peaks exhibited by the resonators. Thus, for the room-temperature-stabilized 9 GHz sapphire-loaded cavity resonator, we observed more than 16 dB improvement in the thermal noise peak contrast relative to the single-channel measurements. The ability of the dual-channel readout system to discriminate between the broad- and narrow-band fluctuations may benefit the search for dark matter, which relies on the use of cryogenic microwave resonators.
FL7 is an ancient ABA-independent inhibitor of PP2C-As regulating plant stress responses
Strain engineering of intrinsic multiferroic coupling in bilayer ScI2
Two-dimensional (2D) sliding ferroelectrics have emerged as promising candidates for next-generation nonvolatile memory technologies. However, integrating magnetic, ferroelectric, and ferrovalley properties within a single material system remains a significant challenge. Here, we propose a strategy combining interlayer sliding and strain engineering to synergistically control magnetism, ferroelectric polarization, magnetic anisotropy energy (MAE), and valley polarization in bilayer ScI2 through first-principles calculations. By altering the stacking order from AA to AB/BA configurations, the magnetic ground state transitions from antiferromagnetic (AFM) to ferromagnetic (FM) ordering, accompanied by the modulation of ferroelectric polarization and valley splitting. External strain further enables precise tuning of these properties: A compressive strain of −2% induces an AFM–FM transition in AB stacked ScI2, while a −6% strain enhances MAE beyond 1 meV. Notably, a tensile strain of 5.71% triggers a semiconductor-to-semimetal transition, transforming the ferrovalley state into a half-valley metal. These findings establish bilayer ScI2 as a versatile platform for the multifunctional device design, offering promising pathways to integrate charge, spin, and valley degrees of freedom in 2D multiferroics.
Structure and mechanism of the broad spectrum CRISPR-associated ring nuclease Crn4
Abstract Type III CRISPR systems detect the presence of RNA from mobile genetic elements (MGE) in prokaryotes, providing antiviral immunity. On activation, the catalytic Cas10 subunit conjugates ATP to form cyclic oligoadenylate (cOA) signalling molecules that activate ancillary effectors, providing an immune response. Cellular ring nucleases degrade cOA to reset the system. Here, we describe the structure and mechanism of a new family of ring nucleases, Crn4, associated with type III-D CRISPR systems. The crystal structure of Crn4 reveals a small homodimeric protein with a fold unrelated to any known ring nuclease or, indeed, any known protein structure. Crn4 degrades a wide range of cOA species to linear oligoadenylates in vitro and ameliorates type III CRISPR immunity in vivo. Phage and plasmids also encode Crn4 orthologues that may function as anti-CRISPRs. These observations expand our understanding of ring nucleases and reveal a new protein fold for cyclic nucleotide recognition.
Revisiting the epitaxial Si3N4 crystalline cap on AlGaN/GaN via evolutionary structure search
In our recent experimental work [Luo et al., Appl. Phys. Lett. 125, 122109 (2024)], we observed that crystalline Si3N4 cap layers, a few nanometers thick, can form in situ on GaN surfaces. Compared with amorphous SiO2 and Al2O3 caps, these crystalline caps yield cleaner GaN/Si3N4 interfaces with fewer defects and improved device metrics. These observations motivate two questions: why does Si3N4 farther from the interface become amorphous as the cap thickens, and what is the actual crystal structure of the interfacial Si3N4? Prior work proposed a defect-wurtzite (DW) model constructed heuristically from β-Si3N4 and the AlGaN lattice constants, but it is significantly higher in energy than β-Si3N4 and disagrees with experiment in both interlayer spacings and electronic bandgap. Using a systematic structure search approach under in-plane lattice constraints commensurate with AlGaN, we identify a lower-energy configuration, denoted Lam-Si3N4, with quasi-two-dimensional (laminar) stacking normal to the interface. Under AlGaN-matched metrics, Lam-Si3N4 is about 60 meV/atom more stable than DW-Si3N4 and reproduces the experimentally observed interlayer spacings more closely. The substantial lattice mismatch explains amorphization when the crystalline cap grows far from the interface. Upon full relaxation, both DW- and Lam-Si3N4 exhibit wide ∼4 eV bandgaps. Under AlGaN constraints, the DW gap collapses to ∼1.88 eV, whereas Lam-Si3N4 maintains a larger ∼2.70 eV gap (for reference, PBE gaps: GaN 1.73 eV, AlN 4.05 eV). The wider gap and improved structural match of Lam-Si3N4 rationalize the superior capping performance and provide guidance for optimizing AlGaN/GaN device encapsulation.
70 km long-range Raman distributed optical fibre sensing through enhanced anti-distortion coding and waveform reconstruction
Abstract The practical implementation of Raman distributed optical fibre sensing has been fundamentally constrained by the inherent low signal-to-noise ratio (SNR), particularly for sensing distance exceeding 30 km. We propose a paradigm that combines enhanced anti-distortion coding processing, advanced Raman scattering waveform reconstruction preprocessing, and Haar wavelet denoising to transcend this physical limitation. The proposed pre-processing framework simultaneously optimises complementary sequences correlation, effectively mitigates disturbances of transient effects and improves sensing performance. The experimental demonstration achieves performance metrics: 70.0 km sensing distance with 1.58 m spatial resolution, while maintaining 0.91 °C measurement accuracy and 5.39 °C temperature resolution. The tripartite synergistic mechanism, consisting of the waveform reconstruction pre-processing framework compensating for and suppressing transient effects, coding gain improving the baseline SNR, and the Haar wavelet transform removing residual noise, breaks through the theoretical trade-off constraint between SNR and sensing distance in traditional schemes. The proposed approach demonstrates a potential for application in the fields of long-range infrastructure monitoring and environmental sensing.
High gain Ga2O3/GaN avalanche photodetector with separated absorption and multiplication structure
The β-Ga2O3/p-GaN heterojunction avalanche photodetector (APD) with separated absorption and multiplication (SAM) structure was fabricated by metal–organic chemical vapor deposition. Through x-ray diffraction and scanning electron microscopy characterization, the Ga2O3 films exhibit relatively high crystalline quality. Through reasonable design of the electron concentration and thickness of the Ga2O3 layers, the device achieves an ultrahigh avalanche gain (Gain) of 1.75 × 107, an external quantum efficiency (EQE) of 4.53 × 107%, and a high responsivity (R) of 9.28 × 104 A/W under 254 nm solar-blind ultraviolet illumination (5 μW/cm2). The working mechanism of SAM-APD was further validated through TCAD simulations. Compared to conventional APDs, the SAM structure can significantly enhance avalanche gain and EQE, thereby improving the weak signal detection level of the APD effectively.
An open-source screening platform accelerates discovery of drug combinations
Switching dynamics of oxygen-vacancy memristors based on cuprate superconductors
Resistive switching phenomena have attracted increased attention over the years because of their technological relevance, particularly for applications like nonvolatile memories and memristors, which are of much interest for emerging neuromorphic computation schemes. Devices based on complex oxides are especially appealing, since these materials present a plethora of functionalities (magnetism, superconductivity, photoconductivity…) and resistive switching mechanisms. Determining their characteristic timescales is crucial, both for fundamental understanding and regarding the potential applications. Here, we analyze the resistive switching dynamics of tunnel junctions between a cuprate superconductor and a metallic counter-electrode, in which memristive behavior stems from an electrochemical redox reaction across their interface. We compare these junctions with similar ones in which a thin oxide ferroelectric layer is placed in between both electrodes, expected to promote faster ferroelectric switching effects. We find that all the junctions show similar dynamics, pointing to oxygen ion exchange as the dominant mechanism in all cases. Interestingly, very strong resistance switching effects are observed down to the 100 ns timescale, thus allowing for applications where fast switching is required, even at cryogenic temperatures at which superconducting effects can be exploited.