Absence of near-ambient superconductivity in LuH2±xNy.

A recent study demonstrated near-ambient superconductivity in nitrogen-doped lutetium hydride1. This stimulated a worldwide interest in exploring room-temperature superconductivity at low pressures. Here, by using a high-pressure and high-temperature synthesis technique, we have obtained nitrogen-doped lutetium hydride (LuH2±xNy), which has a dark-blue colour and a structure with the space group [Formula: see text] as evidenced by X-ray diffraction. This structure is the same as that reported in ref. 1, with a slight difference in lattice constant. Raman spectroscopy of our samples also showed patterns similar to those observed in ref. 1. Energy-dispersive X-ray spectroscopy confirmed the presence of nitrogen in the samples. We observed a metallic behaviour from 350 K to 2 K at ambient pressure. On applying pressures from 2.1 GPa to 41 GPa, we observed a gradual colour change from dark blue to violet to pink-red. By measuring the resistance at pressures ranging from 0.4 GPa to 40.1 GPa, we observed a progressively improved metallic behaviour; however, superconductivity was not observed above 2 K. Temperature dependence of magnetization at high pressure shows a very weak positive signal between 100 K and 320 K, and the magnetization increases with an increase in magnetic field at 100 K. All of these are not expected for superconductivity above 100 K. Thus, we conclude the absence of near-ambient superconductivity in this nitrogen-doped lutetium hydride at pressures below 40.1 GPa.

Accurate Cancer Screening and Prediction of PD-L1-Guided Immunotherapy Efficacy Using Quantum Dot Nanosphere Self-Assembly and Machine Learning.

Accurate quantification of exosomal PD-L1 protein in tumors is closely linked to the response to immunotherapy, but robust methods to achieve high-precision quantitative detection of PD-L1 expression on the surface of circulating exosomes are still lacking. In this work, we developed a signal amplification approach based on aptamer recognition and DNA scaffold hybridization-triggered assembly of quantum dot nanospheres, which enables bicolor phenotyping of exosomes to accurately screen for cancers and predict PD-L1-guided immunotherapeutic effects through machine learning. Through DNA-mediated assembly, we utilized two aptamers for simultaneous ultrasensitive detection of exosomal antigens, which have synergistic roles in tumor diagnosis and treatment prediction, and thus, we achieved better sample classification and prediction through machine-learning algorithms. With a drop of blood, we can distinguish between different cancer patients and healthy individuals and predict the outcome of immunotherapy. This approach provides valuable insights into the development of personalized diagnostics and precision medicine.

Electrochemiluminescence-Based Single-Particle Tracking of the Biomolecules Moving along Intercellular Membrane Nanotubes between Live Cells.

Electrochemiluminescence (ECL) imaging, a rapidly evolving technology, has attracted significant attention in the field of cellular imaging. However, its primary limitation lies in its inability to analyze the motion behaviors of individual particles in live cellular environments. In this study, we leveraged the exceptional ECL properties of quantum dots (QDs) and the excellent electrochemical properties of carbon dots (CDs) to develop a high-brightness ECL nanoprobe (CDs-QDs) for real-time ECL imaging between living cells. This nanoprobe has excellent signal-to-noise ratio imaging capabilities for the single-particle tracking (SPT) of biomolecules. Our finding elucidated the enhanced ECL mechanism of CDs-QDs in the presence of reactive oxygen species through photoluminescence, electrochemistry, and ECL techniques. We further tracked the movement of single particles on membrane nanotubes between live cells and confirmed that the ECL-based SPT technique using CD-QD nanoparticles is an effective approach for monitoring the transport behaviors of biomolecules on membrane nanotubes between live cells. This opens a promising avenue for the advancement of ECL-based single-particle detection and the dynamic quantitative imaging of biomolecules.

In Situ Quantitative Imaging of Plasma Membrane Stiffness in Live Cells Using a Genetically Encoded FRET Sensor.

Cell membrane stiffness is critical for cellular function, with cholesterol and sphingomyelin as pivot contributors. Current methods for measuring membrane stiffness are often invasive, ex situ, and slow in process, prompting the need for innovative techniques. Here, we present a fluorescence resonance energy transfer (FRET)-based protein sensor designed to address these challenges. The sensor consists of two fluorescent units targeting sphingomyelin and cholesterol, connected by a linker that responds to the proximity of these lipids. In rigid membranes, cholesterol and sphingomyelin are in close proximity, leading to an increased FRET signal. We utilized this sensor in combination with confocal microscopy to explore changes in plasma membrane stiffness under various conditions, including differences in osmotic pressure, the presence of reactive oxygen species (ROS) and variations in substrate stiffness. Furthermore, we explored the impact of SARS-CoV-2 on membrane stiffness and the distribution of ACE2 after attachment to the cell membrane. This tool offers substantial potential for future investigations in the field of mechanobiology.

Aromatic and magnetic properties in a series of heavy rare earth-doped Ge6 cluster anions.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe 6 - (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2-TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti-aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth-doped semiconductor materials.

Tailored Polypyrrole Nanofibers as Ion-to-Electron Transduction Membranes for Wearable K+ Sensors.

Conductive polymers are recognized as ideal candidates for the development of noninvasive and wearable sensors for real-time monitoring of potassium ions (K+) in sweat to ensure the health of life. However, the low ion-to-electron transduction efficiency and limited active surface area hamper the development of high-performance sensors for low-concentration K+ detection in the sweat. Herein, a wearable K+ sensor is developed by tailoring the nanostructure of polypyrrole (PPy), serving as an ion-to-electron transduction layer, for accurately and stably tracing the K+ fluctuation in human sweat. The PPy nanostructures can be tailored from nanospheres to nanofibers by controlling the supramolecular assembly process during PPy polymerization. Resultantly, the ion-to-electron transduction efficiency (17-fold increase in conductivity) and active surface area (1.3-fold enhancement) are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofibers-based K+ sensor achieved a high sensitivity of 62 mV decade-1, good selectivity, and solid stability. After being integrated with a temperature sensor, the manufactured wearable sensor realized accurate monitoring of K+ fluctuation in the human sweat.

Ratiometric Fluorescence Probes for In Situ Imaging of Membrane Tension in Live Cells.

Membrane tension is an important physical parameter of describing cellular homeostasis, and it is widely used in the study of cellular processes involving membrane deformation and reorganization, such as cell migration, cell spreading, and cell division. Despite the importance of membrane tension, direct measurement remains difficult. In this work, we developed a ratiometric fluorescent probe sensitive to membrane tension by adjusting the carbon chain structure based on polarity-sensitive fluorophores. The probe is sensitive to changes in membrane tension after cells were subjected to physical or chemical stimuli, such as osmotic shock, lipid peroxidation, and mechanical stress. When the polarity of the plasma membrane increases (the green/red ratio decreases) and the membrane tension increases, the relative magnitude of the membrane tension can be quantitatively calculated by fluorescence ratio imaging. Thus, the probe proved to be an efficient and sensitive membrane tension probe.

Probing the Structural and Electronic Properties of the Anionic and Neutral Tellurium-Doped Boron Clusters TeBnq (n = 3-16, q = 0, -1).

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

Measurements of the gravitational constant using two independent methods.

The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.05 per cent in recent determinations of G suggests that there may be undiscovered systematic errors in the various existing methods. One way to resolve this issue is to measure G using a number of methods that are unlikely to involve the same systematic effects. Here we report two independent determinations of G using torsion pendulum experiments with the time-of-swing method and the angular-acceleration-feedback method. We obtain G values of 6.674184 × 10-11 and 6.674484 × 10-11 cubic metres per kilogram per second squared, with relative standard uncertainties of 11.64 and 11.61 parts per million, respectively. These values have the smallest uncertainties reported until now, and both agree with the latest recommended value within two standard deviations.

Direct visualization of a static incommensurate antiferromagnetic order in Fe-doped Bi2Sr2CaCu2O8+δ.

In cuprate superconductors, due to strong electronic correlations, there are multiple intertwined orders which either coexist or compete with superconductivity. Among them, the antiferromagnetic (AF) order is the most prominent one. In the region where superconductivity sets in, the long-range AF order is destroyed. Yet the residual short-range AF spin fluctuations are present up to a much higher doping, and their role in the emergence of the superconducting phase is still highly debated. Here, by using a spin-polarized scanning tunneling microscope, we directly visualize an emergent incommensurate AF order in the nearby region of Fe impurities embedded in the optimally doped Bi2Sr2CaCu2O8+δ (Bi2212). Remarkably, the Fe impurities suppress the superconducting coherence peaks with the gapped feature intact, but pin down the ubiquitous short-range incommensurate AF order. Our work shows an intimate relation between antiferromagnetism and superconductivity.

Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy.

Systemic lupus erythematosus (SLE) is a prototype inflammatory autoimmune disease, characterized by breakdown of immunotolerance to self-antigens. Renal involvement, known as lupus nephritis (LN), is one of the leading causes of morbidity and a significant contributor to mortality in SLE. Despite current pathophysiological advances, further studies are needed to fully understand complex mechanisms underlying the development and progression of LN. Transcription factors (TFs) are proteins that regulate the expression of genes and play a crucial role in the development and progression of LN. The mechanisms of TF promoting or inhibiting gene expression are complex, and studies have just begun to reveal the pathological roles of TFs in LN. Understanding TFs in the pathogenesis of LN can provide valuable insights into this disease's mechanisms and potentially lead to the development of targeted therapies for its management. This review will focus on recent findings on TFs in the pathogenesis of LN and newly developed TF-targeted therapy in renal inflammation.

Fabrication of Coffee-Ring Nanostructured Membranes for Organic Solvent Nanofiltration.

Organic solvent nanofiltration (OSN) plays important roles in pharmaceutical ingredients purification and solvent recovery. However, the low organic solvent permeance under cross-flow operation of OSN membrane hampers their industrial applications. Herein, we report the construction of coffee-ring structured membrane featuring high OSN permeance. A water-insoluble crystal monomer that dissolved in EtOH/H2O mixed solvent was designed to react with trimesoyl chloride via interfacial polymerization. Owing to the diffusion of EtOH to n-hexane, coffee-ring nanostructure on the support membrane appeared, which served as the template for construction of coffee-ring structured membrane. The optimal nanostructured membrane demonstrated 2.6-fold enhancement in the effective surface area with reduced membrane thickness. Resultantly, the membrane afforded a 2.7-fold enhancement in organic solvent permeance, e.g., ~13 LMH/bar for MeOH, without sacrificing the rejection ability. Moreover, due to the rigid monomer structure, the fabricated membrane shows distinctive running stability in active pharmaceutical ingredients purification and the ability for concentration of medicines.

Micro/Nano-Fabrication of Flexible Poly(3,4-Ethylenedioxythiophene)-Based Conductive Films for High-Performance Microdevices.

With the increasing demands for novel flexible organic electronic devices, conductive polymers are now becoming the rising star for reaching such targets, which has witnessed significant breakthroughs in the fields of thermoelectric devices, solar cells, sensors, and hydrogels during the past decade due to their outstanding conductivity, solution-processing ability, as well as tailorability. However, the commercialization of those devices still lags markedly behind the corresponding research advances, arising from the not high enough performance and limited manufacturing techniques. The conductivity and micro/nano-structure of conductive polymer films are two critical factors for achieving high-performance microdevices. In this review, the state-of-the-art technologies for developing organic devices by using conductive polymers are comprehensively summarized, which will begin with a description of the commonly used synthesis methods and mechanisms for conductive polymers. Next, the current techniques for the fabrication of conductive polymer films will be proffered and discussed. Subsequently, approaches for tailoring the nanostructures and microstructures of conductive polymer films are summarized and discussed. Then, the applications of micro/nano-fabricated conductive films-based devices in various fields are given and the role of the micro/nano-structures on the device performances is highlighted. Finally, the perspectives on future directions in this exciting field are presented.

Artificial Cells for Cellular Behavior Mimicry Induced by Sphingomyelin Degradation.

Sphingomyelinase (SMase), a hydrolase of sphingomyelin (SM) enriched in the outer leaflet of the plasma membrane of mammalian cells, is closely associated with the onset and development of many diseases, but the specific mechanisms of SMase on the cell structure, function, and behavior are not yet fully understood due to the complexity of the cell structure. Artificial cells are minimal biological systems constructed from various molecular components designed to mimic cellular processes, behaviors, and structures, which are excellent models for studying biochemical reactions and dynamic changes in cell membranes. In this work, we presented an artificial cell model that mimics the lipid composition and content of the outer leaflet of mammalian plasma membranes for studying the effect of SMase on cell behavior. The results confirmed that the artificial cells can respond to SM degradation by producing ceramides that enrich and alter the membrane charge and permeability, thus inducing the budding and fission of the artificial cells. Thus, the artificial cells developed here provide a powerful tool to study the mechanism of action of cell membrane lipids on cell biological behavior, paving the way for further molecular mechanism studies.

Transcriptome analysis of liver, gill and intestine in rainbow trout (Oncorhynchus mykiss) symptomatically or asymptomatically infected with Vibrio anguillarum.

Rainbow trout (Oncorhynchus mykiss), an important economic cold-water fish worldwide, is severely threatened by viruses and bacteria in the farming industry. The vibriosis outbreak has caused a significant setback to aquaculture. Vibrio anguillarum, one of the common disease-causing vibriosis associated with severe lethal vibriosis in aquaculture, infects fish mainly by adsorption and invasion of the skin, gills, lateral line and intestine. To investigate the defense mechanism of rainbow trout against the pathogen after infection with Vibrio anguillarum, trout were intraperitoneally injected by Vibrio anguillarum and divided into symptomatic group (SG) and asymptomatic group (AG) according to the phenotype. RNA-Seq technology was used to evaluate the transcriptional signatures of liver, gill and intestine of trout injected with Vibrio anguillarum (SG and AG) and corresponding control groups (CG(A) and CG(B)). The GO and KEGG enrichment analyses were used to investigate the mechanisms underlying the differences in susceptibility to Vibrio anguillarum. Results showed that in SG, immunomodulatory genes in the cytokine network were activated and tissue function-related genes were down-regulated, while apoptosis mechanisms were activated. However, AG responded to Vibrio anguillarum infection by activating complement related immune defenses, while metabolism and function related genes were up-regulated. Conclusively, a rapid and effective immune and inflammatory response can successfully defend Vibrio anguillarum infection. However, a sustained inflammatory response can lead to tissue and organ damage and cause death. Our results may provide a theoretical basis for breeding rainbow trout for disease resistance.

Bamboo-like Vortex Chains Confined in Canals with Suppressed Superconductivity and Standing Waves of Quasiparticles.

The vortex core can be regarded as a nanoscale confined system for quasiparticles in a type-II superconductor. It is very interesting to investigate the interplay between the vortex core and other microscopic quantum confined systems. We observe band-like canals with the width of about 15 nm on the surface of KCa2(Fe1-xNix)4As4F2 (x = 0.05) by scanning tunneling microscopy. Some canals suppress superconductivity and confine parallel standing waves due to the quasiparticle interference. Upon magnetic fields being applied, some elongated vortices are formed within canals showing bamboo-like one-dimensional vortex chains. Interestingly, the confined vortex cores are elongated roughly along the perpendicular direction of canals, and the local density of states at positive and negative energies shows an in-phase oscillation at zero field; but, it becomes out-of-phase crossing the vortex cores. Our work reveals a new type of vortex patterns in confined canals and its interplay with the quasiparticle interference.

DUSP6 Deficiency Attenuates Neurodegeneration after Global Cerebral Ischemia.

Transient global cerebral ischemia (tGCI) resulting from cardiac arrest causes selective neurodegeneration in hippocampal CA1 neurons. Although the effect is clear, the underlying mechanisms directing this process remain unclear. Previous studies have shown that phosphorylation of Erk1/2 promotes cell survival in response to tGCI. DUSP6 (also named MKP3) serves as a cytosolic phosphatase that dephosphorylates Erk1/2, but the role of DUSP6 in tGCI has not been characterized. We found that DUSP6 was specifically induced in the cytoplasm of hippocampal CA1 neurons 4 to 24 h after tGCI. DUSP6-deficient mice showed normal spatial memory acquisition and retention in the Barnes maze. Impairment of spatial memory acquisition and retention after tGCI was attenuated in DUSP6-deficient mice. Neurodegeneration after tGCI, revealed by Fluoro-Jade C and H&E staining, was reduced in the hippocampus of DUSP6-deficient mice and DUSP6 deficiency enhanced the phosphorylation and nuclear translocation of Erk1/2 in the hippocampal CA1 region. These data support the role of DUSP6 as a negative regulator of Erk1/2 signaling and indicate the potential of DUSP6 inhibition as a novel therapeutic strategy to treat neurodegeneration after tGCI.

Acetylation-Mimic Mutation of TRIM28-Lys304 to Gln Attenuates the Interaction with KRAB-Zinc-Finger Proteins and Affects Gene Expression in Leukemic K562 Cells.

TRIM28/KAP1/TIF1ß is a crucial epigenetic modifier. Genetic ablation of trim28 is embryonic lethal, although RNAi-mediated knockdown in somatic cells yields viable cells. Reduction in TRIM28 abundance at the cellular or organismal level results in polyphenism. Posttranslational modifications such as phosphorylation and sumoylation have been shown to regulate TRIM28 activity. Moreover, several lysine residues of TRIM28 are subject to acetylation, but how acetylation of TRIM28 affects its functions remains poorly understood. Here, we report that, compared with wild-type TRIM28, the acetylation-mimic mutant TRIM28-K304Q has an altered interaction with Krüppel-associated box zinc-finger proteins (KRAB-ZNFs). The TRIM28-K304Q knock-in cells were created in K562 erythroleukemia cells by CRISPR-Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein nuclease 9) gene editing method. Transcriptome analysis revealed that TRIM28-K304Q and TRIM28 knockout K562 cells had similar global gene expression profiles, yet the profiles differed considerably from wild-type K562 cells. The expression levels of embryonic-related globin gene and a platelet cell marker integrin-beta 3 were increased in TRIM28-K304Q mutant cells, indicating the induction of differentiation. In addition to the differentiation-related genes, many zinc-finger-proteins genes and imprinting genes were activated in TRIM28-K304Q cells; they were inhibited by wild-type TRIM28 via binding with KRAB-ZNFs. These results suggest that acetylation/deacetylation of K304 in TRIM28 constitutes a switch for regulating its interaction with KRAB-ZNFs and alters the gene regulation as demonstrated by the acetylation mimic TRIM28-K304Q.

Engineered Lipidic Nanomaterials Inspired by Sphingomyelin Metabolism for Cancer Therapy.

Sphingomyelin (SM) and its metabolites are crucial regulators of tumor cell growth, differentiation, senescence, and programmed cell death. With the rise in lipid-based nanomaterials, engineered lipidic nanomaterials inspired by SM metabolism, corresponding lipid targeting, and signaling activation have made fascinating advances in cancer therapeutic processes. In this review, we first described the specific pathways of SM metabolism and the roles of their associated bioactive molecules in mediating cell survival or death. We next summarized the advantages and specific applications of SM metabolism-based lipidic nanomaterials in specific cancer therapies. Finally, we discussed the challenges and perspectives of this emerging and promising SM metabolism-based nanomaterials research area.

Lipocalin-2 mediates the rejection of neural transplants.

Lipocalin-2 (LCN2) has been implicated in promoting apoptosis and neuroinflammation in neurological disorders; however, its role in neural transplantation remains unknown. In this study, we cultured and differentiated Lund human mesencephalic (LUHMES) cells into human dopaminergic-like neurons and found that LCN2 mRNA was progressively induced in mouse brain after the intrastriatal transplantation of human dopaminergic-like neurons. The induction of LCN2 protein was detected in a subset of astrocytes and neutrophils infiltrating the core of the engrafted sites, but not in neurons and microglia. LCN2-immunoreactive astrocytes within the engrafted sites expressed lower levels of A1 and A2 astrocytic markers. Recruitment of microglia, neutrophils, and monocytes after transplantation was attenuated in LCN2 deficiency mice. The expression of M2 microglial markers was significantly elevated and survival of engrafted neurons was markedly improved after transplantation in LCN2 deficiency mice. Brain type organic cation transporter (BOCT), the cell surface receptor for LCN2, was induced in dopaminergic-like neurons after differentiation, and treatment with recombinant LCN2 protein directly induced apoptosis in dopaminergic-like neurons in a dose-dependent manner. Our results, therefore, suggested that LCN2 is a neurotoxic factor for the engrafted neurons and a modulator of neuroinflammation. LCN2 inhibition may be useful in reducing rejection after neural transplantation.