EM-COGLOAD: An investigation into age and cognitive load detection using eye tracking and deep learning.

Alzheimer's Disease is the most prevalent neurodegenerative disease, and is a leading cause of disability among the elderly. Eye movement behaviour demonstrates potential as a non-invasive biomarker for Alzheimer's Disease, with changes detectable at an early stage after initial onset. This paper introduces a new publicly available dataset: EM-COGLOAD (available at https://osf.io/zjtdq/, DOI: 10.17605/OSF.IO/ZJTDQ). A dual-task paradigm was used to create effects of declined cognitive performance in 75 healthy adults as they carried out visual tracking tasks. Their eye movement was recorded, and time series classification of the extracted eye movement traces was explored using a range of deep learning techniques. The results of this showed that convolutional neural networks were able to achieve an accuracy of 87.5% when distinguishing between eye movement under low and high cognitive load, and 76% when distinguishing between the oldest and youngest age groups.

Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence.

Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein equilibrium. This disturbance limits nuclear protein availability and hinders polymerase initiation and engagement, reducing gene transcription. Concurrently, it promptly disrupts nucleolar transcription, ribosomal processes, and nuclear exporting, resulting in a translational shutdown. Prolonged exosome depletion induces nuclear structural changes resembling senescent cells, including aberrant chromatin compaction, chromocenter disassembly, and intensified heterochromatic foci. These effects suggest that the dynamic turnover of nuclear RNA orchestrates crosstalk between essential processes to optimize cellular function. Disruptions in nuclear RNA homeostasis result in systemic functional decline, altering the cell state and promoting senescence.

Connexin 43 Prevents Radiation-Induced Intestinal Damage via the Ca2+-Dependent PI3K/Akt Signaling Pathway.

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.

Role of crosstalk between synovial cells and chondrocytes in osteoarthritis (Review).

Osteoarthritis (OA) is a low-grade, nonspecific inflammatory disease that affects the entire joint. This condition is characterized by synovitis, cartilage erosion, subchondral bone defects, and subpatellar fat pad damage. There is mounting evidence demonstrating the significance of crosstalk between synovitis and cartilage destruction in the development of OA. To comprehensively explore the phenotypic alterations of synovitis and cartilage destruction, it is important to elucidate the crosstalk mechanisms between chondrocytes and synovial cells. Furthermore, the updated iteration of single-cell sequencing technology reveals the interaction between chondrocyte and synovial cells. In the present review, the histological and pathological alterations between cartilage and synovium during OA progression are described, and the mode of interaction and molecular mechanisms between synovial cells and chondrocytes in OA, both of which affect the OA process mainly by altering the inflammatory environment and cellular state, are elucidated. Finally, the current OA therapeutic approaches are summarized and emerging therapeutic targets are reviewed in an attempt to provide potential insights into OA treatment.

Genetic Screening of Haploid Neural Stem Cells Reveals that Nfkbia and Atp2b4 are Key Regulators of Oxidative Stress in Neural Precursors.

Neurological diseases are expected to become the leading cause of death in the next decade. Although little is known about it, the interaction between oxidative stress and inflammation is harmful to the nervous system. To find an advanced tool for neural genetics, mouse haploid neural stem cells (haNSCs) from the somite of chimeric mouse embryos at E8.5 is established. The haNSCs present a haploid neural progenitor identity for long-term culture, promising to robustly differentiate into neural subtypes and being able to form cerebral organoids efficiently. Thereafter, haNSC mutants via a high-throughput approach and screened targets of oxidative stress is generated using the specific mutant library. Deletion of Nfkbia (the top hit among the insertion mutants) reduces damage from reactive oxygen species (ROS) in NSCs exposed to H2O2. Transcriptome analysis revealed that Atp2b4 is upregulated significantly in Nfkbia-null NSCs and is probably responsible for the observed resistance. Additionally, overexpression of Atp2b4 itself can increase the survival of NSCs in the presence of H2O2, suggesting that Atp2b4 is closely involved in this resistance. Herein, a powerful haploid system is presented to study functional genetics in neural lineages, shedding light on the screening of critical genes and drugs for neurological diseases.

A von-Neumann-like photonic processor and its application in studying quantum signature of chaos.

Photonic quantum computation plays an important role and offers unique advantages. Two decades after the milestone work of Knill-Laflamme-Milburn, various architectures of photonic processors have been proposed, and quantum advantage over classical computers has also been demonstrated. It is now the opportune time to apply this technology to real-world applications. However, at current technology level, this aim is restricted by either programmability in bulk optics or loss in integrated optics for the existing architectures of processors, for which the resource cost is also a problem. Here we present a von-Neumann-like architecture based on temporal-mode encoding and looped structure on table, which is capable of multimode-universal programmability, resource-efficiency, phase-stability and software-scalability. In order to illustrate these merits, we execute two different programs with varying resource requirements on the same processor, to investigate quantum signature of chaos from two aspects: the signature behaviors exhibited in phase space (13 modes), and the Fermi golden rule which has not been experimentally studied in quantitative way before (26 modes). The maximal program contains an optical interferometer network with 1694 freely-adjustable phases. Considering current state-of-the-art, our architecture stands as the most promising candidate for real-world applications.

A joint brain extraction and image quality assessment framework for fetal brain MRI slices.

Brain extraction and image quality assessment are two fundamental steps in fetal brain magnetic resonance imaging (MRI) 3D reconstruction and quantification. However, the randomness of fetal position and orientation, the variability of fetal brain morphology, maternal organs around the fetus, and the scarcity of data samples, all add excessive noise and impose a great challenge to automated brain extraction and quality assessment of fetal MRI slices. Conventionally, brain extraction and quality assessment are typically performed independently. However, both of them focus on the brain image representation, so they can be jointly optimized to ensure the network learns more effective features and avoid overfitting. To this end, we propose a novel two-stage dual-task deep learning framework with a brain localization stage and a dual-task stage for joint brain extraction and quality assessment of fetal MRI slices. Specifically, the dual-task module compactly contains a feature extraction module, a quality assessment head and a segmentation head with feature fusion for simultaneous brain extraction and quality assessment. Besides, a transformer architecture is introduced into the feature extraction module and the segmentation head. We utilize a multi-step training strategy to guarantee a stable and successful training of all modules. Finally, we validate our method by a 5-fold cross-validation and ablation study on a dataset with fetal brain MRI slices in different qualities, and perform a cross-dataset validation in addition. Experiments show that the proposed framework achieves very promising performance.

Bright and stable monomeric green fluorescent protein derived from StayGold.

The high brightness and photostability of the green fluorescent protein StayGold make it a particularly attractive probe for long-term live-cell imaging; however, its dimeric nature precludes its application as a fluorescent tag for some proteins. Here, we report the development and crystal structures of a monomeric variant of StayGold, named mBaoJin, which preserves the beneficial properties of its precursor, while serving as a tag for structural proteins and membranes. Systematic benchmarking of mBaoJin against popular green fluorescent proteins and other recently introduced monomeric and pseudomonomeric derivatives of StayGold established mBaoJin as a bright and photostable fluorescent protein, exhibiting rapid maturation and high pH/chemical stability. mBaoJin was also demonstrated for super-resolution, long-term live-cell imaging and expansion microscopy. We further showed the applicability of mBaoJin for neuronal labeling in model organisms, including Caenorhabditis elegans and mice.

Charge-density wave mediated quasi-one-dimensional Kondo lattice in stripe-phase monolayer 1T-NbSe2.

The heavy fermion physics is dictated by subtle competing exchange interactions, posing a challenge to their understanding. One-dimensional (1D) Kondo lattice model has attracted special attention in theory, because of its exact solvability and expected unusual quantum criticality. However, such experimental material systems are extremely rare. Here, we demonstrate the realization of quasi-1D Kondo lattice behavior in a monolayer van der Waals crystal NbSe2, that is driven into a stripe phase via Se-deficient line defects. Spectroscopic imaging scanning tunneling microscopy measurements and first-principles calculations indicate that the stripe-phase NbSe2 undergoes a novel charge-density wave transition, creating a matrix of local magnetic moments. The Kondo lattice behavior is manifested as a Fano resonance at the Fermi energy that prevails the entire film with a high Kondo temperature. Importantly, coherent Kondo screening occurs only in the direction of the stripes. Upon approaching defects, the Fano resonance exhibits prominent spatial 1D oscillations along the stripe direction, reminiscent of Kondo holes in a quasi-1D Kondo lattice. Our findings provide a platform for exploring anisotropic Kondo lattice behavior in the monolayer limit.

Rapid and large-scale synthesis of MoS2via ultraviolet laser-assisted technology for photodetector applications.

Two-dimensional transition metal dichalcogenide (TMDC) thin films have been extensively employed in microelectronics research. Molybdenum disulfide (MoS2), as one of prominent candidates of this class, has been applied in photodetectors, integrated electronic devices, gas sensing, and electrochemical catalysis, owing to its extraordinary optoelectronic, chemical, and mechanical properties. Synthesis of MoS2crystal film is the key to its application. However, the reported technology revealed several drawbacks, containing limited surface area, prolonged high-temperature environment, and unsatisfying crystallinity. In order to enhance the convenience of MoS2applications, there is a pressing need for optimized fabrication technology, which could be quicker, with a large area, with adequate crystallinity and heat-saving. In this work, we presented an ultraviolet laser-assisted synthesis technology, accomplishing rapid growth (with the growth rate of about 40 um s-1) of centimeter-scale MoS2films at room temperature. To achieve this, we self-assembled a displaceable reaction chamber system, coupled with krypton fluoride ultraviolet pulse laser. The laser motion speed and trajectory could be customized in the software, allowing the maskless patterning of crystal films. As application, we exhibited a photodetector with the integration of synthesized MoS2and lead sulfide colloidal quantum dots (PbS CQDs), displaying broadband photodetection from ultraviolet, visible to near-infrared spectrum (365 ~ 1550 nm), with the detectivity of 109~ 1010Jones, and the rising time of 0.2 ~ 0.3 s. This work not only demonstrated a high-process-efficiency synthesis of TMDC materials, but also has opened up new opportunities for ultraviolet laser used in optoelectronics.

Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer.

Cell-free RNA (cfRNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cfRNA isolation technologies due to the low abundance and instability of cfRNA. Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids (containing cfRNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework (MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cfRNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cfRNA in serum from patients with liver cancer was described and a cfRNA signature with six cfRNAs was identified to diagnose liver cancer with high diagnostic efficiency (area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

Haplotype-phased genome unveils the butylphthalide biosynthesis and homoploid hybrid origin of Ligusticum chuanxiong.

Butylphthalide is one of the first-line drugs for ischemic stroke therapy, while no biosynthetic enzyme for butylphthalide has been reported. Here, we present a haplotype-resolved genome of Ligusticum chuanxiong, a long-cultivated and phthalide-rich medicinal plant in Apiaceae. On the basis of comprehensive screening, four Fe(II)- and 2-oxoglutarate-dependent dioxygenases and two CYPs were mined and further biochemically verified as phthalide C-4/C-5 desaturases (P4,5Ds) that effectively promoted the forming of (S)-3-n-butylphthalide and butylidenephthalide. The substrate promiscuity and functional redundancy featured for P4,5Ds may contribute to the high phthalide diversity in L. chuanxiong. Notably, comparative genomic evidence supported L. chuanxiong as a homoploid hybrid with Ligusticum sinense as a potential parent. The two haplotypes demonstrated exceptional structure variance and diverged around 3.42 million years ago. Our study is an icebreaker for the dissection of phthalide biosynthetic pathway and reveals the hybrid origin of L. chuanxiong, which will facilitate the metabolic engineering for (S)-3-n-butylphthalide production and breeding for L. chuanxiong.

Connexin 43 Prevents Radiation-Induced Intestinal Damage via the Ca2+-Dependent PI3K/Akt Signaling Pathway.

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.

Nutrients recovery by coupled bioreactor of heterotrophic ammonia assimilation and microbial fuel cell in saline wastewater.

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.

Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27-Driven Itch Pathway.

Chronic itch is a common and complex symptom often associated with skin diseases such as atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undefined. We sought to investigate IL-27 function in itch using tissue-specific transgenic mice, various itch models, behavior scoring, RNA sequencing, and cytokine/kinase array. Our findings show that IL-27 receptors were overexpressed in human AD skin. Intradermal IL-27 injection failed to directly induce itch in mice but upregulated skin protease-activated receptor 2 (PAR2) transcripts, a key factor in itch and AD. IL-27 activated human keratinocytes, increasing PAR2 transcription and activity. Coinjection of SLIGRL (PAR2 agonist) and IL-27 in mice heightened PAR2-mediated itch. In addition, IL-27 boosted BST2 transcription in sensory neurons and keratinocytes. BST2 was upregulated in AD skin, and its injection in mice induced itch-like response. BST2 colocalized with sensory nerve branches in AD skin from both human and murine models. Sensory neurons released BST2, and mice with sensory neuron-specific BST2 knockout displayed reduced itch responses. Overall, this study provides evidence that skin IL-27/PAR2 and neuronal IL-27/BST2 axes are implicated in cutaneous inflammation and pruritus. The discovery of neuronal BST2 in pruritus shed light on BST2 in the itch cascade.

Bubble Unidirectional Transportation on Multipath Aerophilic Surfaces by Adjusting the Surface Microstructure.

Comprehending and controlling the behavior of bubbles on solid surfaces is of significant importance in various fields including catalysis and drag reduction, both industrially and scientifically. Herein, Inspired by the superaerophilic properties of the lotus leaf surface, a series of asymmetrically patterned aerophilic surfaces were prepared by utilizing a facile mask-spraying method for directional transport of underwater bubbles. The ability of bubbles to undergo self-driven transportation in an asymmetric pattern is attributed to the natural tendency of bubbles to move toward regions with lower surface energy. In this work, the microstructure of the aerophilic surface is demonstrated as a critical element that influences the self-driven transport of bubbles toward regions of lower surface energy. The microstructure characteristic affects the energy barrier of forming a continuous gas film on the final regions. We classify three distinct bubble behaviors on the aerophilic surface, which align with three different underwater gas film evolution states: Model I, Model II, and Model III. Furthermore, utilizing the energy difference between the energy barrier that forms a continuous gas film and the gas-gas merging, gas-liquid microreaction in a specific destination on the multiple paths can be easily realized by preinjecting a bubble in the final region. This work provides a new view of the microevolutionary process for the diffusion, transport, and merging behavior of bubbles upon contact with an aerophilic pattern surface.

Altering Spin Distribution of Tb2Pc3 via Molecular Chirality Manipulation.

Manipulating the chirality of the spin-polarized electronic state is pivotal for understanding many unusual quantum spin phenomena, but it has not been achieved at the single-molecule level. Here, using scanning tunneling microscopy and spectroscopy (STM/STS), we successfully manipulate the chirality of spin distribution in a triple-decker single-molecule magnet tris(phthalocyaninato)bis(terbium(III)) (Tb2Pc3), which is evaporated on a Pb(111) substrate via molecular beam epitaxy. The otherwise achiral Tb2Pc3 becomes chiral after being embedded into the self-assembled monolayer films of bis(phthalocyaninato)terbium(III) (TbPc2). The chirality of the spin distribution in Tb2Pc3 is manifested via the spatial mapping of its Kondo resonance state from its ligand orbital. Our first-principles calculations revealed that the spin and molecular chirality are associated with a small rotation followed by a structural distortion of the top Pc, consistent with the experimental observation. By constructing tailored molecular clusters with the STM tip, a single Tb2Pc3 molecule can be manipulated among achiral and differently handed chiral configurations of spin distributions reversibly. This paves the way for designing chiral spin enantiomers for fundamental studies and developing functional spintronic devices.

Preparation of MoS2@PDA-Modified Polyimide Films with High Mechanical Performance and Improved Electrical Insulation.

Polyimide (PI) has been widely used in cable insulation, thermal insulation, wind power protection, and other fields due to its high chemical stability and excellent electrical insulation and mechanical properties. In this research, a modified PI composite film (MoS2@PDA/PI) was obtained by using polydopamine (PDA)-coated molybdenum disulfide (MoS2) as a filler. The low interlayer friction characteristics and high elastic modulus of MoS2 provide a theoretical basis for enhancing the flexible mechanical properties of the PI matrix. The formation of a cross-linking structure between a large number of active sites on the surface of the PDA and the PI molecular chain can effectively enhance the breakdown field strength of the film. Consequently, the tensile strength of the final sample MoS2@PDA/PI film increased by 44.7% in comparison with pure PI film, and the breakdown voltage strength reached 1.23 times that of the original film. It can be seen that the strategy of utilizing two-dimensional (2D) MoS2@PDA nanosheets filled with PI provides a new modification idea to enhance the mechanical and electrical insulation properties of PI films.

Seeds exhibit the most stable elemental composition with nitrogen addition in an Inner Mongolian grassland.

Variation in biomass elemental composition of grassland plants may have important implications for ecosystem functioning in response to global change. However, relevant studies have mostly focused on variation of nitrogen (N) and phosphorus (P) concentrations in plant leaves, while few studies have evaluated other elements and plant organs of grassland species. Here, we examined the effects of N addition on multi-element concentrations, and analyzed their patterns across different organs (leaf, stem, root and seed) of five plant species in a steppe community of the Inner Mongolian grassland. Our results showed that seeds exhibited the most stable elemental composition with N addition, and that manganese (Mn) and iron (Fe) concentrations were substantially more variable than macro-elements in response to N addition. In particular, we identified a set of significant negative relationships between elemental concentrations and their corresponding CVs (coefficients of variation) for all plant organs as a whole and for each individual organ. We further found that changes in soil pH and the availability of soil nutrients contributed mostly to variation in the biomass elemental composition of major plants in this community. These findings are important for accurately assessing the effects of N deposition on the biochemical cycling of nutrient elements in grassland ecosystems, and provide critical clues for developing effective approaches to adaptively managing grassland resources as well as mitigating the impact of global change on the dryland ecosystems in the Mongolia Plateau.