Infection with wild-type SARS-CoV-2 elicits broadly neutralizing and protective antibodies against omicron subvariants.

The omicron variants of SARS-CoV-2 have substantial ability to escape infection- and vaccine-elicited antibody immunity. Here, we investigated the extent of such escape in nine convalescent patients infected with the wild-type SARS-CoV-2 during the first wave of the pandemic. Among the total of 476 monoclonal antibodies (mAbs) isolated from peripheral memory B cells, we identified seven mAbs with broad neutralizing activity to all variants tested, including various omicron subvariants. Biochemical and structural analysis indicated the majority of these mAbs bound to the receptor-binding domain, mimicked the receptor ACE2 and were able to accommodate or inadvertently improve recognition of omicron substitutions. Passive delivery of representative antibodies protected K18-hACE2 mice from infection with omicron and beta SARS-CoV-2. A deeper understanding of how the memory B cells that produce these antibodies could be selectively boosted or recalled can augment antibody immunity against SARS-CoV-2 variants.

Recover then aggregate: unified cross-modal deep clustering with global structural information for single-cell data.

Single-cell cross-modal joint clustering has been extensively utilized to investigate the tumor microenvironment. Although numerous approaches have been suggested, accurate clustering remains the main challenge. First, the gene expression matrix frequently contains numerous missing values due to measurement limitations. The majority of existing clustering methods treat it as a typical multi-modal dataset without further processing. Few methods conduct recovery before clustering and do not sufficiently engage with the underlying research, leading to suboptimal outcomes. Additionally, the existing cross-modal information fusion strategy does not ensure consistency of representations across different modes, potentially leading to the integration of conflicting information, which could degrade performance. To address these challenges, we propose the 'Recover then Aggregate' strategy and introduce the Unified Cross-Modal Deep Clustering model. Specifically, we have developed a data augmentation technique based on neighborhood similarity, iteratively imposing rank constraints on the Laplacian matrix, thus updating the similarity matrix and recovering dropout events. Concurrently, we integrate cross-modal features and employ contrastive learning to align modality-specific representations with consistent ones, enhancing the effective integration of diverse modal information. Comprehensive experiments on five real-world multi-modal datasets have demonstrated this method's superior effectiveness in single-cell clustering tasks.

Supt16 haploinsufficiency causes neurodevelopment disorder by disrupting MAPK pathway in neural stem cells.

Chromatin regulators constitute a fundamental means of transcription regulation, which have been implicated in neurodevelopment and neurodevelopment disorders (NDDs). Supt16, one of candidate genes for NDDs, encodes the large subunit of facilitates chromatin transcription. However, the underlying mechanisms remain poorly understood. Here, Supt16+/- mice was generated, modeling the neurodevelopment disorder. Abnormal cognitive and social behavior was observed in the Supt16  +/- mice. Simultaneously, the number of neurocytes in the cerebral cortex and hippocampus is decreased, which might be resulted from the impairment of mouse neural stem cells (mNSCs) in the SVZ. Supt16 haploinsufficiency affects the proliferation and apoptosis of mNSCs. As the RNA-seq and chromatic immunoprecipitation sequencing assays showed, Supt16 haploinsufficiency disrupts the stemness of mNSCs by inhibiting MAPK signal pathway. Thus, this study demonstrates a critical role of Supt16 gene in the proliferation and apoptosis of mNSCs and provides a novel insight in the pathogenesis of NDDs.

DPNN-ac4C: A Dual-Path Neural Network with self-attention mechanism for identification of N4­acetylcytidine (ac4C) in mRNA.

MOTIVATION: The modification of N4-acetylcytidine (ac4C) in RNA is a conserved epigenetic mark that plays a crucial role in post-transcriptional regulation, mRNA stability, and translation efficiency. Traditional methods for detecting ac4C modifications are laborious and costly, necessitating the development of efficient computational approaches for accurate identification of ac4C sites in mRNA. RESULTS: We present DPNN-ac4C, a dual-path neural network with a self-attention mechanism for the identification of ac4C sites in mRNA. Our model integrates embedding modules, bidirectional GRU networks, convolutional neural networks, and self-attention to capture both local and global features of RNA sequences. Extensive evaluations demonstrate that DPNN-ac4C outperforms existing models, achieving an AUROC of 91.03%, accuracy of 82.78%, MCC of 65.78%, and specificity of 84.78% on an independent test set. Moreover, DPNN-ac4C exhibits robustness under the Fast Gradient Method (FGM) attack, maintaining a high level of accuracy in practical applications. AVAILABILITY AND IMPLEMENTATION: The model code and dataset are publicly available on GitHub (https://github.com/shock1ng/DPNN-ac4C).

Mechanical memory based on chromatin and metabolism remodeling promotes proliferation and smooth muscle differentiation in mesenchymal stem cells.

Stem cells respond and remember mechanical cues from the microenvironment, which modulates their therapeutic effects. Chromatin organization and energy metabolism regulate the stem cell fate induced by mechanical cues. However, the mechanism of mechanical memory is still unclear. This study aimed to investigate the effects of mechanical amplitude, frequency, duration, and stretch cycle on mechanical memory in mesenchymal stem cells. It showed that the amplitude was the dominant parameter to the persistence of cell alignment. F-actin, paxillin, and nuclear deformation are more prone to be remolded than cell alignment. Stretching induces transcriptional memory, resulting in greater transcription upon subsequent reloading. Cell metabolism displays mechanical memory with sustained mitochondrial fusion and increased ATP production. The mechanical memory of chromatin condensation is mediated by histone H3 lysine 27 trimethylation, leading to much higher smooth muscle differentiation efficiency. Interestingly, mechanical memory can be transmitted based on direct cell-cell interaction, and stretched cells can remodel the metabolic homeostasis of static cells. Our results provide insight into the underlying mechanism of mechanical memory and its potential benefits for stem cell therapy.

Defect Engineering of Ultrasmall TiO2 Nanoparticles Enables Highly Efficient Photocatalysts for Solar H2 Production from Woody Biomass.

The conversion of woody biomass to H2 through photocatalysis provides a sustainable strategy to generate renewable hydrogen fuel but was limited by the slow decomposition rate of woody biomass. Here, we fabricate ultrasmall TiO2 nanoparticles with tunable concentration of oxygen vacancy defects (VO-TiO2) as highly efficient photocatalysts for photocatalytic conversion of woody biomass to H2. Owing to the positive role of oxygen vacancy in reducing energy barrier for the generation of •OH which was the critical species to oxidize woody biomass, the obtained VO-TiO2 achieves rapid photocatalytic conversion of α-cellulose and poplar wood chip to H2 in the presence of Pt nanoclusters as the cocatalyst. As expected, the highest H2 generation rate in α-cellulose and poplar wood chip system respectively achieve 1146 and 59 µmol h-1 g-1, and an apparent quantum yield of 4.89% at 380 nm was obtained in α-cellulose aqueous solution.

Epigenetic Aging and Musculoskeletal Outcomes in a Cohort of Women Living With HIV.

BACKGROUND: The relationship between accelerated epigenetic aging and musculoskeletal outcomes in women with HIV (WWH) has not been studied. METHODS: We measured DNA methylation age using the Infinium MethylationEPIC BeadChip in a cohort from the Women's Interagency HIV Study (n = 190) with measures of bone mineral density (BMD) and physical function. We estimated 6 biomarkers of epigenetic aging-epigenetic age acceleration (EAA), extrinsic EAA, intrinsic EAA, GrimAge, PhenoAge, and DNA methylation-estimated telomere length-and evaluated associations of epigenetic aging measures with BMD and physical function. We also performed epigenome-wide association studies to examine associations of DNA methylation signatures with BMD and physical function. RESULTS: This study included 118 WWH (mean age, 49.7 years; 69% Black) and 72 without HIV (mean age, 48.9 years; 69% Black). WWH had higher EAA (mean ± SD, 1.44 ± 5.36 vs -1.88 ± 5.07; P < .001) and lower DNA methylation-estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P < .001) than women without HIV. There were no significant associations between accelerated epigenetic aging and BMD. Rather, measures of accelerated epigenetic aging were associated with lower physical function. CONCLUSIONS: Accelerated epigenetic aging was observed in WWH as compared with women without HIV and was associated with lower physical function in both groups.

EIF4A3-Induced CircDHTKD1 regulates glycolysis in non-small cell lung cancer via stabilizing PFKL.

Lung cancer (LC) is one of the malignancies with the highest incidence and mortality in the world, approximately 85% of which is non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) exert multiple roles in NSCLC occurrence and development. The sequencing results in previous literature have illustrated that multiple circRNAs exhibit upregulation in NSCLC. We attempted to figure out which circRNA exerts an oncogenic role in NSLCL progression. RT-qPCR evaluated circDHTKD1 level in NSCLC tissue specimens and cells. Reverse transcription as well as RNase R digestion assay evaluated circDHTKD1 circular characterization in NSCLC cells. FISH determined circDHTKD1 subcellular distribution in NSCLC cells. Loss- and gain-of-function assays clarified circDHTKD1 role in NSCLC cell growth, tumour growth and glycolysis. Bioinformatics and RIP and RNA pull-down assessed association of circDHTKD1 with upstream molecule Eukaryotic initiation factor 4A-III (EIF4A3) or downstream molecule phosphofructokinase-1 liver type (PFKL) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) in NSCLC cells. Rescue assays assessed regulatory function of PFKL in circDHTKD1-meidated NSCLC cellular phenotypes. CircDHTKD1 exhibited upregulation and stable circular nature in NSCLC cells. EIF4A3 upregulated circDHTKD1 in NSCLC cells. CircDHTKD1 exerted a promoting influence on NSCLC cell malignant phenotypes and tumour growth. CircDHTKD1 exerted a promoting influence on NSCLC glucose metabolism. CircDHTKD1 exerts a promoting influence on NSCLC glucose metabolism through PFKL upregulation. RIP and RNA pull-down showed that circDHTKD1 could bind to IGF2BP, PFKL could bind to IGF2BP2, and circDHTKD1 promoted the binding of PFKL to IGF2BP2. In addition, RT-qPCR showed that IGF2BP2 knockdown promoted PFKL mRNA degradation, suggesting that IGF2BP2 stabilized PFKL in NSCLC cells. CircDHTKD1 exhibits upregulation in NSCLC. We innovatively validate that EIF4A3-triggered circDHTKD1 upregulation facilitates NSCLC glycolysis through recruiting m6A reader IGF2BP2 to stabilize PFKL, which may provide a new direction for seeking targeted therapy plans of NSCLC.

Comprehensive analysis of Alfin-like transcription factors associated with drought and salt stresses in wheat (Triticum aestivum L.).

BACKGROUND: Alfin-like proteins are a kind of plant-specific transcription factors, and play vital roles in plant growth, development and stress responses. RESULTS: In this study, a total of 27 Alfin-like transcription factors were identified in wheat. TaAL genes were unevenly distributed on chromosome. Phylogenetic analysis showed TaAL genes were divided into AL-B and AL-C subfamilies, and TaALs with closer evolutionary relationships generally shared more similar exon-intron structures and conserved motifs. The cis-acting element analysis showed MBS, ABRE and CGTCA-motif were the most common in TaAL promoters. The interacting proteins and downstream target genes of TaAL genes were also investigated in wheat. The transcriptome data and real-time PCR results indicated TaAL genes were differentially expressed under drought and salt stresses, and TaAL1-B was significantly up-regulated in response to drought stress. In addition, association analysis revealed that TaAL1-B-Hap-I allelic variation had significantly higher survival rate compared to TaAL1-B-Hap-II under drought stress. CONCLUSIONS: These results will provide vital information to increase our understanding of the Alfin-like gene family in wheat, and help us in breeding better wheat varieties in the future.

Regioselective On-Surface Synthesis of [3]Triangulene Graphene Nanoribbons.

The integration of low-energy states into bottom-up engineered graphene nanoribbons (GNRs) is a robust strategy for realizing materials with tailored electronic band structure for nanoelectronics. Low-energy zero-modes (ZMs) can be introduced into nanographenes (NGs) by creating an imbalance between the two sublattices of graphene. This phenomenon is exemplified by the family of [n]triangulenes (n ∈ N). Here, we demonstrate the synthesis of [3]triangulene-GNRs, a regioregular one-dimensional (1D) chain of [3]triangulenes linked by five-membered rings. Hybridization between ZMs on adjacent [3]triangulenes leads to the emergence of a narrow band gap, Eg,exp ∼ 0.7 eV, and topological end states that are experimentally verified using scanning tunneling spectroscopy. Tight-binding and first-principles density functional theory calculations within the local density approximation corroborate our experimental observations. Our synthetic design takes advantage of a selective on-surface head-to-tail coupling of monomer building blocks enabling the regioselective synthesis of [3]triangulene-GNRs. Detailed ab initio theory provides insights into the mechanism of on-surface radical polymerization, revealing the pivotal role of Au-C bond formation/breakage in driving selectivity.

Antitumor activity of α-pinene in T-cell tumors.

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α-pinene as an antitumor agent for the treatment of T-cell tumors. We found that α-pinene inhibited the proliferation of hematologic malignancies, especially in T-cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α-pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.

Semi-Coherent Heterointerface Engineering via In Situ Phase Transition for Enhanced Sodium/Lithium-Ions Storage.

To improve ion transport kinetics and electronic conductivity between the different phases in sodium/lithium-ion battery (LIB/SIB) anodes, heterointerface engineering is considered as a promising strategy due to the strong built-in electric field. However, the lattice mismatch and defects in the interphase structure can lead to large grain boundary resistance, reducing the ion transport kinetics and electronic conductivity. Herein, monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface embedded in 3D connected Nitrogen-doped carbon yolk-shell matrix (Fe3Se4-Fe7Se8@NC) is obtained via an in situ phase transition process. Such semi-coherent heterointerface between Fe3Se4 and Fe7Se8 shows the matched interfacial lattice and strong built-in electric field, resulting in the low interface impedance and fast reaction kinetics. Moreover, the yolk-shell structure is designed to confine all monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface nanoparticles, improving the structural stability and inhibiting the volume expansion effect. In particular, the 3D carbon bridge between multi-yolks shell structure improves the electronic conductivity and shortens the ion transport path. Therefore, the efficient reversible pseudocapacitance and electrochemical conversion reaction are enabled by the Fe3Se4-Fe7Se8@NC, leading to the high specific capacity of 439 mAh g-1 for SIB and 1010 mAh g-1 for LIB. This work provides a new strategy for constructing heterointerface of the anode for secondary batteries.

A Portable Integrated Electrochemical Sensing System for On-Site Nitrite Detection in Food.

Ensuring an appropriate nitrite level in food is essential to keep the body healthy. However, it still remains a huge challenge to offer a portable and low-cost on-site food nitrite analysis without any expensive equipment. Herein, a portable integrated electrochemical sensing system (IESS) is developed to achieve rapid on-site nitrite detection in food, which is composed of a low-cost disposable microfluidic electrochemical patch for few-shot nitrite detection, and a reusable smartphone-assisted electronic device based on self-designed circuit board for signal processing and wireless transmission. The electrochemical patch based on MXene-Ti3C2Tx/multiwalled carbon nanotubes-cyanocobalamin (MXene/MWCNTs-VB12)-modified working electrode achieves high sensitivity of 10.533 µA mm-1 and low nitrite detection limit of 4.22 µm owing to strong electron transfer ability of hybrid MXene/MWCNTs conductive matrix and high nitrite selectivity of VB12 bionic enzyme-based ion-selective layer. Moreover, the portable IESS can rapidly collect pending testing samples through a microfluidic electrochemical patch within 1.0 s to conduct immediate nitrite analysis, and then wirelessly transmit data from a signal-processing electronic device to a smartphone via Bluetooth module. Consequently, this proposed portable IESS demonstrates rapid on-site nitrite analysis and wireless data transmission within one palm-sized electronic device, which would pave a new avenue in food safety and personal bespoke therapy.

Tunable Magnetic Coupling in Graphene Nanoribbon Quantum Dots.

Carbon-based quantum dots (QDs) enable flexible manipulation of electronic behavior at the nanoscale, but controlling their magnetic properties requires atomically precise structural control. While magnetism is observed in organic molecules and graphene nanoribbons (GNRs), GNR precursors enabling bottom-up fabrication of QDs with various spin ground states have not yet been reported. Here the development of a new GNR precursor that results in magnetic QD structures embedded in semiconducting GNRs is reported. Inserting one such molecule into the GNR backbone and graphitizing it results in a QD region hosting one unpaired electron. QDs composed of two precursor molecules exhibit nonmagnetic, antiferromagnetic, or antiferromagnetic ground states, depending on the structural details that determine the coupling behavior of the spins originating from each molecule. The synthesis of these QDs and the emergence of localized states are demonstrated through high-resolution atomic force microscopy (HR-AFM), scanning tunneling microscopy (STM) imaging, and spectroscopy, and the relationship between QD atomic structure and magnetic properties is uncovered. GNR QDs provide a useful platform for controlling the spin-degree of freedom in carbon-based nanostructures.

Metabolomic profiling of single enlarged lysosomes.

Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. The accuracy and reliability of this technique were validated by supporting previous findings, such as the transportability of lysosomal cationic amino acids transporters such as PQLC2 and the lysosomal trapping of lysosomotropic, hydrophobic weak base drugs such as lidocaine. We derived metabolites from single lysosomes in various cell types and classified lysosomes into five major subpopulations based on their chemical and biological divergence. Senescence and carcinoma altered metabolic profiles of lysosomes in a type-specific manner. Thus, SLMS can open more avenues for investigating heterogeneous lysosomal metabolic changes during physiological and pathological processes.

Wheat TaPYL9-involved signalling pathway impacts plant drought response through regulating distinct osmotic stress-associated physiological indices.

The abscisic acid (ABA) signalling pathway plays a crucial role in plants' response to drought stress. In this study, we aimed to characterize the impact of an ABA signalling module, which consisted of TaPYL9 and its downstream partners in Triticum aestivum, on plant drought adaptation. Our results showed that TaPYL9 protein contains conserved motifs and targets plasma membrane and nucleus after being sorted by the endoplasmic reticulum. In addition, TaPYL9 transcripts in both roots and leaves were significantly upregulated in response to drought stress. We conducted glucuronidase (GUS) histochemical staining analysis for transgenic plants carrying a truncated TaPYL9 promoter, which suggested that cis-elements associate with ABA and drought response, such as ABRE, DRE and recognition sites MYB and MYC, regulating the gene transcription under drought conditions. Using protein interaction assays (i.e., yeast two-hybrid, bimolecular fluorescence complementation (BiFC), co-immunoprecipitation (Co-IP) and in vitro pull-down), we demonstrated interactions between the intermediate segment of TaPYL9, the intermediate segment of TaPP2C6, the N-terminus of TaSnRK2.8 and the C-terminus of the transcription factor TabZIP1 in wheat, indicating the involvement of TaPYL9 in the constitution of an ABA signalling module, namely TaPYL9/TaPP2C6/TaSnRK2.8/TabZIP1. Transgene analysis revealed that TaPYL9, TaSnRK2.8 and TabZIP1 positively regulated drought response, while TaPP2C6 negatively regulated it, and that these genes were closely associated with the regulation of stomata movement, osmolyte accumulation and ROS homeostasis. Electrophoretic mobility shift (EMSA) and transcriptioal activation assays indicated that TabZIP1 interacted promoters of TaP5CS2, TaSLAC1-1 and TaCAT2 and activated transcription of these genes, which regulated proline biosynthesis, stomata movement and ROS scavenging upon drought signalling, respectively. Furthermore, we found that the transcripts of TaPYL9 and stress-responsive genes were positively correlated with yields in wheat cultivars under field drought conditions. Altogether, our findings suggest that the TaPYL9-involved signalling pathway significantly regulates drought response by modulating osmotic stress-associated physiological processes in T. aestivum.

Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes.

BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood. RESULTS: We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers. CONCLUSIONS: We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.

Nicotinamide N -methyltransferase promotes M2 macrophage polarization by IL6 and MDSC conversion by GM-CSF in gallbladder carcinoma.

BACKGROUND AND AIMS: Nicotinamide N -methyltransferase (NNMT), an enzyme responsible for the methylation of nicotinamide, is involved in many metabolic pathways in adipose tissue and the liver. However, the role of NNMT in editing the tumor immune microenvironment is not well understood. APPROACH AND RESULTS: Here, we identified that NNMT can promote IL6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by decreasing the tri-methyl-histone H3 levels on the promoters of IL6 and CSF2 (encoding GM-CSF) and CCAAT/Enhancer Binding Protein, an essential transcription factor for IL6 expression, thus promoting differentiation of macrophages into M2 type tumor-associated macrophages and generation of myeloid-derived suppressor cells from peripheral blood mononuclear cells. Treatment of xenografted tumor models overexpressing NNMT gallbladder carcinoma (GBC) cells with the NNMT inhibitor JBSNF-000088 resulted in compromised tumor development and decreased expression levels of IL6, GM-CSF, tumor-associated macrophage marker CD206, and myeloid-derived suppressor cell marker CD33 but increased expression levels of CD8. In addition, elevated expression of NNMT in tumors of patients with GBC was correlated with increased expression levels of CD206 and CD33 but with decreased levels of CD8 and survival of patients. CONCLUSIONS: These data highlight the critical role of NNMT in GBC progression. Inhibition of NNMT by JBSNF-000088 is a potential molecular target for GBC immunotherapy.

Vibration disturbance compensation in in situ confocal microscopy.

In situ microscopic measurement, conducted within the natural environment of a material or device, offers precise observations directly at the sample location, mitigating potential damage or deformation during transport. However, the inherent vibration of microscopic measurement equipment can introduce blurring and distortion to images, compromising measurement accuracy. This study proposes employing an acceleration sensor to detect microprobe vibrations and subsequently calculates three-dimensional coordinate displacements to compensate for measurement discrepancies. This approach can diminish the adverse effects of vibration on measurement outcomes within the order of hundreds of nanometers. Experimental results demonstrated the efficacy of this method in mitigating vibration artifact stripes or irregularities with a displacement amplitude I = sinc2[a(z - b)] ranging from ∼0.2 to 5.2 µm and a frequency spanning ∼7.9-18.8 Hz. Moreover, the lateral resolution of the probe attained 212 nm. Notably, the measurement error associated with the standard step height was decreased from 2.32 to 0.03 µm.

Oxymatrine mitigates Aspergillus fumigatus keratitis by suppressing fungal activity and restricting pyroptosis.

Fungal keratitis (FK) is a refractory keratitis caused by excessive inflammation and fungal damage. Excessive inflammation can lead to tissue damage and corneal opacity, resulting in a poor prognosis for FK. Oxymatrine (OMT) is a natural alkaloid, which has rich pharmacological effects, such as antioxidant and anti-inflammation. However, its antifungal activity and the mechanism of action in FK have not been elucidated. This study confirmed that OMT suppressed Aspergillus fumigatus growth, biofilm formation, the integrity of fungal cell and conidial adherence. OMT not only effectively reduced corneal fungal load but also inflammation responses. OMT lessened the recruitment of neutrophils and macrophages in FK. In addition, OMT up-regulated the expression of Nrf2 and down-regulated the expression of IL-18, IL-1ß, caspase-1, NLRP3 and GSDMD. Pre-treatment with Nrf2 inhibitor up-regulated the expression of IL-1ß, IL-18, caspase-1, NLRP3 and GSDMD supressed by OMT. In conclusion, OMT has efficient anti-inflammatory and antifungal effects by suppressing fungal activity and restricting pyroptosis via Nrf2 pathway. OMT is considered as a potential option for the treatment of FK.