Flexible scaffold-based cheminformatics approach for polypharmacological drug design.

Effective treatments for complex central nervous system (CNS) disorders require drugs with polypharmacology and multifunctionality, yet designing such drugs remains a challenge. Here, we present a flexible scaffold-based cheminformatics approach (FSCA) for the rational design of polypharmacological drugs. FSCA involves fitting a flexible scaffold to different receptors using different binding poses, as exemplified by IHCH-7179, which adopted a "bending-down" binding pose at 5-HT2AR to act as an antagonist and a "stretching-up" binding pose at 5-HT1AR to function as an agonist. IHCH-7179 demonstrated promising results in alleviating cognitive deficits and psychoactive symptoms in mice by blocking 5-HT2AR for psychoactive symptoms and activating 5-HT1AR to alleviate cognitive deficits. By analyzing aminergic receptor structures, we identified two featured motifs, the "agonist filter" and "conformation shaper," which determine ligand binding pose and predict activity at aminergic receptors. With these motifs, FSCA can be applied to the design of polypharmacological ligands at other receptors.

Nuclear morphology is shaped by loop-extrusion programs.

It is well established that neutrophils adopt malleable polymorphonuclear shapes to migrate through narrow interstitial tissue spaces1-3. However, how polymorphonuclear structures are assembled remains unknown4. Here we show that in neutrophil progenitors, halting loop extrusion-a motor-powered process that generates DNA loops by pulling in chromatin5-leads to the assembly of polymorphonuclear genomes. Specifically, we found that in mononuclear neutrophil progenitors, acute depletion of the loop-extrusion loading factor nipped-B-like protein (NIPBL) induced the assembly of horseshoe, banded, ringed and hypersegmented nuclear structures and led to a reduction in nuclear volume, mirroring what is observed during the differentiation of neutrophils. Depletion of NIPBL also induced cell-cycle arrest, activated a neutrophil-specific gene program and conditioned a loss of interactions across topologically associating domains to generate a chromatin architecture that resembled that of differentiated neutrophils. Removing NIPBL resulted in enrichment for mega-loops and interchromosomal hubs that contain genes associated with neutrophil-specific enhancer repertoires and an inflammatory gene program. On the basis of these observations, we propose that in neutrophil progenitors, loop-extrusion programs produce lineage-specific chromatin architectures that permit the packing of chromosomes into geometrically confined lobular structures. Our data also provide a blueprint for the assembly of polymorphonuclear structures, and point to the possibility of engineering de novo nuclear shapes to facilitate the migration of effector cells in densely populated tumorigenic environments.

Multiple forces facilitate the aquatic acrobatics of grasshopper and bioinspired robot.

Aquatic locomotion is challenging for land-dwelling creatures because of the high degree of fluidity with which the water yields to loads. We surprisingly found that the Chinese rice grasshopper Oxya chinensis, known for its terrestrial acrobatics, could swiftly launch itself off the water's surface in around 25 ms and seamlessly transition into flight. Biological observations showed that jumping grasshoppers use their front and middle legs to tilt up bodies first and then lift off by propelling the water toward the lower back with hind legs at angular speeds of up to 18°/ms, whereas the swimming grasshoppers swing their front and middle legs in nearly horizontal planes and move hind legs less violently (~8°/ms). Force measurement and model analysis indicated that the weight support could be achieved by hydrostatics which are proportionate to the mass of the grasshoppers, while the propulsions for motion are derived from the controlled limb-water interactions (i.e., the hydrodynamics). After learning the structural and behavioral strategies of the grasshoppers, a robot was created and was capable of swimming and jumping on the water surface like the insects, further demonstrating the effectiveness of decoupling the challenges of aquatic locomotion by the combined use of the static and dynamic hydro forces. This work not only uncovered the combined mechanisms responsible for facilitating aquatic acrobatics in this species but also laid a foundation for developing bioinspired robots that can locomote across multiple media.

The ergodicity question when imaging DNA conformation using liquid cell electron microscopy.

Assessing the ergodicity of graphene liquid cell electron microscope measurements, we report that loop states of circular DNA interconvert reversibly and that loop numbers follow the Boltzmann distribution expected for this molecule in bulk solution, provided that the electron dose is low (80-keV electron energy and electron dose rate 1-20 e- Å-2 s-1). This imaging technique appears to act as a "slow motion" camera that reveals equilibrated distributions by imaging the time average of a few molecules without the need to image a spatial ensemble.

Nanopipette dynamic microscopy unveils nano coffee ring.

Liquid-phase electron microscopy (LP-EM) imaging has revolutionized our understanding of nanosynthesis and assembly. However, the current closed geometry limits its application for open systems. The ubiquitous physical process of the coffee-ring phenomenon that underpins materials and engineering science remains elusive at the nanoscale due to the lack of experimental tools. We introduce a quartz nanopipette liquid cell with a tunable dimension that requires only standard microscopes. Depending on the imaging condition, the open geometry of the nanopipette allows the imaging of evaporation-induced pattern formation, but it can also function as an ordinary closed-geometry liquid cell where evaporation is negligible despite the nano opening. The nano coffee-ring phenomenon was observed by tracking individual nanoparticles in an evaporating nanodroplet created from a thin liquid film by interfacial instability. Nanoflows drive the assembly and disruption of a ring pattern with the absence of particle-particle correlations. With surface effects, nanoflows override thermal fluctuations at tens of nanometers, in which nanoparticles displayed a "drunken man trajectory" and performed work at a value much smaller than kBT.

Suppressing Zn pulverization with three-dimensional inert-cation diversion dam for long-life Zn metal batteries.

Tremendous attention has been paid to the water-associated side reactions and zinc (Zn) dendrite growth on the electrode-electrolyte interface. However, the Zn pulverization that can cause continuous depletion of active Zn metal and exacerbate hydrogen evolution is severely neglected. Here, we disclose that the excessive Zn feeding that causes incomplete crystallization is responsible for Zn pulverization formation through analyzing the thermodynamic and kinetics process of Zn deposition. On the basis, we introduce 1-ethyl-3-methylimidazolium cations (EMIm+) into the electrolyte to form a Galton-board-like three-dimensional inert-cation (3DIC) region. Modeling test shows that the 3DIC EMIm+ can induce the Zn2+ flux to follow in a Gauss distribution, thus acting as elastic sites to buffer the perpendicular diffusion of Zn2+ and direct the lateral diffusion, thus effectively avoiding the local Zn2+ accumulation and irreversible crystal formation. Consequently, anti-pulverized Zn metal deposition behavior is achieved with an average Coulombic efficiency of 99.6% at 5 mA cm-2 over 2,000 cycles and superb stability in symmetric cell over 1,200 h at -30 °C. Furthermore, the Zn||KVOH pouch cell can stably cycle over 1,200 cycles at 2 A g-1 and maintain a capacity of up to 12 mAh.

Whole-genome sequencing of allotetraploid bermudagrass reveals the origin of Cynodon and candidate genes for salt tolerance.

Bermudagrass (Cynodon dactylon) is a globally distributed, extensively used warm-season turf and forage grass with high tolerance to salinity and drought stress in alkaline environments. However, the origin of the species and genetic mechanisms for salinity tolerance in the species are basically unknown. Accordingly, we set out to study evolution divergence events in the Cynodon genome and to identify genes for salinity tolerance. We developed a 604.0 Mb chromosome-level polyploid genome sequence for bermudagrass 'A12359' (n = 18). The C. dactylon genome comprises 2 complete sets of homoeologous chromosomes, each with approximately 30 000 genes, and most genes are conserved as syntenic pairs. Phylogenetic study showed that the initial Cynodon species diverged from Oropetium thomaeum approximately 19.7-25.4 million years ago (Mya), the A and B subgenomes of C. dactylon diverged approximately 6.3-9.1 Mya, and the bermudagrass polyploidization event occurred 1.5 Mya on the African continent. Moreover, we identified 82 candidate genes associated with seven agronomic traits using a genome-wide association study, and three single-nucleotide polymorphisms were strongly associated with three salt resistance genes: RAP2-2, CNG channels, and F14D7.1. These genes may be associated with enhanced bermudagrass salt tolerance. These bermudagrass genomic resources, when integrated, may provide fundamental insights into evolution of diploid and tetraploid genomes and enhance the efficacy of comparative genomics in studying salt tolerance in Cynodon.

Landscape Heterogeneity Explains the Genetic Differentiation of a Forest Bird across the Sino-Himalayan Mountains.

Mountains are the world's most important centers of biodiversity. The Sino-Himalayan Mountains are global biodiversity hotspot due to their extremely high species richness and endemicity. Ample research investigated the impact of the Qinghai-Tibet Plateau uplift and Quaternary glaciations in driving species diversification in plants and animals across the Sino-Himalayan Mountains. However, little is known about the role of landscape heterogeneity and other environmental features in driving diversification in this region. We utilized whole genomes and phenotypic data in combination with landscape genetic approaches to investigate population structure, demography, and genetic diversity in a forest songbird species native to the Sino-Himalayan Mountains, the red-billed leiothrix (Leiothrix lutea). We identified 5 phylogeographic clades, including 1 in the East of China, 1 in Yunnan, and 3 in Tibet, roughly consistent with differences in song and plumage coloration but incongruent with traditional subspecies boundaries. Isolation-by-resistance model best explained population differentiation within L. lutea, with extensive secondary contact after allopatric isolation leading to admixture among clades. Ecological niche modeling indicated relative stability in the extent of suitable distribution areas of the species across Quaternary glacial cycles. Our results underscore the importance of mountains in the diversification of this species, given that most of the distinct genetic clades are concentrated in a relatively small area in the Sino-Himalayan Mountain region, while a single shallow clade populates vast lower-lying areas to the east. This study highlights the crucial role of landscape heterogeneity in promoting differentiation and provides a deep genomic perspective on the mechanisms through which diversity hotspots form.

Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for Antitumor Therapy.

The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.

The Efficacy and Safety of an Intra-articular Dual-Acting Antibacterial Agent (TNP-2092) for Implant Infection-Associated Methicillin-Resistant Staphylococcus aureus.

Owing to the presence of microbial biofilm on the implant, the eradication of biofilm-associated infections poses a challenge for antibiotic therapies. The study aimed to investigate the efficacy and safety of the novel antibiotic agent TNP-2092 in the context of implant infections. In vivo, rats with periprosthetic joint infection (PJI) treated with antibiotics showed an increase in body weight and decrease in swelling, temperature, and width of knee, compared with the control group. Meanwhile, inflammatory markers in synovium and serum were decreased in the TNP-2092 group, consistent with the pathological results. Moreover, TNP-2092 was effective in eliminating bacteria and disruption biofilm formation, and further alleviated the abnormal bone absorption and reactive bone changes around the prosthesis. In conclusion, intra-articular injection of TNP-2092 is safe and effective in treating knee PJI in a rat model. The study provides a foundation for the future utilization of TNP-2092 in the management of implant-related infections.

High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT.

OBJECTIVE: Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC. DESIGN: Metabolite library screening disclosed that palmitic acid (PA) could activate AKT. In vivo and in vitro palmitoylation assay were employed to detect AKT palmitoylation. Diverse cell and mouse models, including generation of AKT1C77S and AKT1C224S knock-in cells, Zdhhc17 and Zdhhc24 knockout mice and Akt1C224S knock-in mice were employed. Human liver tissues from patients with NASH and HCC, hydrodynamic transfection mouse model, high-fat/high-cholesterol diet (HFHCD)-induced NASH/HCC mouse model and high-fat and methionine/choline-deficient diet (HFMCD)-induced NASH mouse model were also further explored for our mechanism studies. RESULTS: By screening a metabolite library, PA has been defined to activate AKT by promoting its palmitoyl modification, an essential step for growth factor-induced AKT activation. Biologically, a high-fat diet could promote AKT kinase activity, thereby promoting NASH and liver cancer. Mechanistically, palmitoyl binding anchors AKT to the cell membrane in a PIP3-independent manner, in part by preventing AKT from assembling into an inactive polymer. The palmitoyltransferases ZDHHC17/24 were characterised to palmitoylate AKT to exert oncogenic effects. Interestingly, the anti-obesity drug orlistat or specific penetrating peptides can effectively attenuate AKT palmitoylation and activation by restricting PA synthesis or repressing AKT modification, respectively, thereby antagonising liver tumorigenesis. CONCLUSIONS: Our findings elucidate a novel fine-tuned regulation of AKT by PA-ZDHHC17/24-mediated palmitoylation, and highlight tumour therapeutic strategies by taking PA-restricted diets, limiting PA synthesis, or directly targeting AKT palmitoylation.

Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression.

Tumor-associated macrophages (TAMs) are key regulators in tumor progression, but the precise role of bone marrow-derived monocytes (Mons) as TAM precursors and their dynamic phenotypes regulated by the tumor microenvironment (TME) remain unclear. Here, we developed an optimized microproteomics workflow to analyze low-cell-number mouse myeloid cells. We sorted TAMs and their corresponding Mons (1 × 105 per sample) from individual melanoma mouse models at both the early and late stages. We established the protein expression profiles for these cells by mass spectrometry. Subsequently, we analyzed the dynamics phenotypes of TAMs and identified a characteristic protein expression profile characterized by upregulated cholesterol metabolism and downregulated immune responses during tumor progression. Moreover, we found the downregulation of both STAT5 and PYCARD expression not only in late-stage TAMs but also in late-stage Mons, indicating a loss of the ability to induce inflammatory responses prior to Mons infiltration into TME. Taken together, our study provides valuable insights into the progression-dependent transitions between TAMs and their precursor cells, as well as the cross-organ communications of tumor and bone marrow.

Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co-expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein-protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages. Functional validation through in vitro and in vivo experiments demonstrates the pivotal role of FCGR2A in macrophage polarization and IDD progression. Mechanistically, FCGR2A knockdown suppresses M1 macrophage polarization and NF-κB phosphorylation while enhancing M2 polarization and STAT3 activation, leading to ameliorated IDD in animal models. This study sheds light on the regulatory function of FCGR2A in macrophage polarization, offering novel insights for IDD intervention strategies. KEY POINTS: This study unveils the role of FCGR2A in intervertebral disc (IVD) degeneration (IDD). FCGR2A knockdown mitigates IDD in cellular and animal models. Single-cell RNA-sequencing uncovers diverse macrophage subpopulations in degenerated IVDs. This study reveals the molecular mechanism of FCGR2A in regulating macrophage polarization. This study confirms the role of the NF-κB/STAT3 pathway in regulating macrophage polarization in IDD.

Indolent T-Cell/Natural Killer-Cell Lymphomas/Lymphoproliferative Disorders of the Gastrointestinal Tract-What Have We Learned in the Last Decade?

Primary gastrointestinal (GI) T-cell and natural killer (NK)-cell lymphomas/lymphoproliferative disorders (LPD) are uncommon, and they are usually aggressive in nature. However, T-cell and NK-cell lymphoma/LPD of the GI tract with indolent clinical course has been reported over the past 2 decades. Indolent T-cell LPD was formally proposed a decade ago in 2013 and 4 years later recognized as a provisional entity by the revised fourth edition of WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in 2017. Indolent T-cell LPD of the GI tract has been changed to indolent T-cell lymphoma of the GI tract as a distinct entity by the fifth edition of WHO Classification of Haematolymphoid Tumours, but the International Consensus Classification of mature lymphoid neoplasms prefers indolent clonal T-cell LPD of the GI tract instead. In the past decade, indolent lymphoma/LPD of the GI tract has been expanded to NK cells, and as such, indolent NK-cell LPD of the GI tract was recognized as an entity by both the fifth edition of WHO Classification of Haematolymphoid Tumours and the International Consensus Classification. The underlying genetic/molecular mechanisms of both indolent T-cell lymphoma/LPD of the GI tract and indolent NK-cell LPD of the GI tract have been recently discovered. In this review, we describe the history; salient clinical, cytohistomorphologic, and immunohistochemical features; and genetic/genomic landscape of both entities. In addition, we also summarize the mimics and differential diagnosis. Finally, we propose future directions with regard to the pathogenesis and clinical management.

LINC00629, a HOXB4-downregulated long noncoding RNA, inhibits glycolysis and ovarian cancer progression by destabilizing c-Myc.

Ovarian cancer (OC) cells typically reprogram their metabolism to promote rapid proliferation. However, the role of long noncoding RNAs (lncRNAs) in the metabolic reprogramming of ovarian cancer, especially in glucose metabolic reprogramming, remains largely unknown. LINC00629 has been reported in our previous study to promote osteosarcoma progression. Upregulated LINC00629 was found to enhance the growth-suppressive effect of apigenin on oral squamous cell carcinoma. However, the precise function of LINC00629 in ovarian cancer development remains poorly understood. In this study, we found that LINC00629 was significantly downregulated in OC tissues and that low LINC00629 expression was associated with poor survival. Inhibition of LINC00629 was required for increased glycolysis activity and cell proliferation in ovarian cancer. In vivo, overexpression of LINC00629 dramatically inhibited tumor growth and lung metastasis. Mechanistically, LINC00629 interacted with and destabilized c-Myc, leading to its ubiquitination and proteasome degradation, further resulting in increased expression of downstream glycolysis-related genes and glucose metabolic reprogramming in OC. Interestingly, HOXB4 bound to the LINC00629 promoter and inhibited its transcription, indicating that LINC00629 is a transcriptional target of HOXB4. Collectively, these findings establish a direct role for LINC00629 in suppressing glucose metabolism, and HOXB4/LINC00629/c-Myc might serve as a potential biomarker and an effective therapeutic strategy for OC cancer treatment.

Exogenous hydrogen sulfide prevents SOD2 degradation to safeguard renal function in diabetic kidney disease.

Diabetic kidney disease (DKD) is a major contributor to chronic kidney disease. Hydrogen sulfide (H2S) serves as an endogenous gaseous signaling molecule capable of safeguarding renal function within the context of DKD. However, the underlying mechanisms need to be elucidated. This study was undertaken to unveil the mechanisms by which H2S counteracts against DKD. Utilizing mice and human renal tubular epithelial (HK-2) cells, we demonstrated a reduction in cystathionine-γ-lyase/H2S levels within renal tissues of db/db mice and in HK-2 cells subjected to hyperglycemic and hyperlipidemic environments. Notably, we observed that sodium hydrosulfide (NaHS) supplementation could serve as an exogenous source of H2S. Exogenous H2S exhibited the capacity to mitigate the accumulation of reactive oxygen species and attenuate the degradation of superoxide dismutase 2 (SOD2) by Lon protease homolog 1 induced by hyperglycemia and hyperlipidemia, thus affording cellular protection against mitochondrial apoptosis. Consequently, NaHS treatment led to decreased serum levels of blood urea nitrogen and serum creatinine, reflecting alleviated renal damage and thereby preserving renal function in db/db mice. Based on these findings, we propose that exogenous H2S exerts a protective role against DKD by inhibiting SOD2 degradation.

Self-Assembled Perylene Diimide (PDI) Nanowire Sensitized In2O3@MgIn2S4 S-Scheme Heterojunction as Photoelectrochemical Biosensing Platform for the Detection of CA15-3.

Inorganic/organic heterojunctions show promising applications as high-performance sensing platforms for photoelectrochemical (PEC) immunosensors. This work reports constructing a PEC biosensor for CA15-3 based on a self-assembled perylene diimide (PDI) nanowire sensitized In2O3@MgIn2S4 S-scheme heterojunction platform. P-type semiconductor Cu2O nanoparticles were designed as a signal burst source and were used as immunoassay labels. The carboxyl group on self-assembled PDI nanowires eliminates the step of additional surface functionalization for covalent immobilization of the capture elements. The π-π stacking of PDI enhances electron generation efficiency, while the carboxylic acid groups on PDI promote electron transfer. The performance of the constructed sensor was validated using CA15-3 as a model. The experimental results showed that the sensor based on In2O3@MgIn2S4/PDI has excellent selectivity, stability, and reproducibility, and can sensitively detect CA15-3 in the range of 0.001-100 U·mL-1 with the detection limit of 0.00056 U·mL-1. The sensor has a broad application prospect. It is hoped that this research work based on the unique advantages of the organic compound PDI will inspire other researchers to design light-responsive materials and promote the development of the field of photoelectrochemical sensing.

Double-Amplified Electrochemiluminescence Immunoassay Sensor for Highly Sensitive Detection of CA19-9 Using a Ternary Semiconductor CdSSe.

In this paper, an electrochemiluminescence (ECL) immunosensor for ultrasensitive detection of CA19-9 was constructed using ternary compound CdSSe nanoparticles as ECL emitter. The immunosensor employs Cu2S and gold-doped diindium trioxide (Au-In2O3) nanocubes as coreaction accelerators to achieve a double-amplification strategy. In general, a hexagonal maple leaf-shaped Cu2S with a large surface area was selected as the template, and the in situ growth of CdSSe on its surface was achieved using a hydrothermal method. The presence of Cu2S not only inhibited the aggregation of CdSSe nanoparticles to reduce their surface energy but also acted as an ECL cathode coreaction promoter, facilitating the generation of SO4•-. Consequently, the ECL intensity of CdSSe was significantly enhanced, and the reduction potential was significantly lower. In addition, the template method was employed to synthesize Au-In2O3 nanocubes, which offers the advantage of directly connecting materials with antibodies, resulting in a more stable construction of the immunosensor. Furthermore, In2O3 serves as a coreaction promoter, enabling the amplification strategy for ECL intensity of CdSSe, thus contributing to the enhanced sensitivity and performance of the immunosensor. The constructed immunosensor exhibited a wide linear range (100 µU mL-1 to 100 U mL-1) and a low detection limit of 80 µU mL-1, demonstrating its high potential and practical value for sensitive detection of CA19-9.

Sub-bundle based analysis reveals the role of human optic radiation in visual working memory.

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function.

Novel Lignin-Functionalized Waterborne Epoxy Composite Coatings with Excellent Anti-Aging, UV Resistance, and Interfacial Anti-Corrosion Performance.

Developing high-performance lignin anti-corrosive waterborne epoxy (WEP) coatings is conducive to the advancement of environmentally friendly coatings and the value-added utilization of lignin. In this work, a functionalized biomass waterborne epoxy composite coating is prepared using quaternized sodium lignosulfonate (QLS) as a functional nanofiller for mild carbon steel protection. The results showed that QLS has excellent dispersion and interface compatibility within WEP, and its abundant phenolic hydroxyl, sulfonate, quaternary ammonium groups, and nanoparticle structure endowed the coating with excellent corrosion inhibition and superior barrier properties. The corrosion inhibition efficiency of 100 mg L-1 QLS in carbon steel immersed in a 3.5 wt% NaCl solution reached 95.76%. Furthermore, the coating maintained an impedance modulus of 2.29 × 106 Ω cm2 (|Z|0.01 Hz) after being immersed for 51 days in the high-salt system. In addition, QLS imparted UV-blocking properties and thermal-oxygen aging resistance to the coating, as evidenced by a |Z|0.01 Hz of 1.04 × 107 Ω cm2 after seven days of UV aging while still maintaining a similar magnitude as before aging. The green lignin/WEP functional coatings effectively withstand the challenging outdoor environment characterized by high salt concentration and intense UV radiation, thereby demonstrating promising prospects for application in metal protection.