HyGAnno: hybrid graph neural network-based cell type annotation for single-cell ATAC sequencing data.

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno leverages genome-wide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was assessed across various datasets, showcasing its strengths in precise cell annotation, generating interpretable cell embeddings, robustness to noisy reference data and adaptability to tumor tissues.

Light-wave dynamic control of magnetism.

The enigmatic interplay between electronic and magnetic phenomena observed in many early experiments and outlined in Maxwell's equations propelled the development of modern electromagnetism1. Today, the fully controlled evolution of the electric field of ultrashort laser pulses enables the direct and ultrafast tuning of the electronic properties of matter, which is the cornerstone of light-wave electronics2-7. By contrast, owing to the lack of first-order interaction between light and spin, the magnetic properties of matter can only be affected indirectly and on much longer timescales, through a sequence of optical excitations and subsequent rearrangement of the spin structure8-16. Here we introduce the regime of ultrafast coherent magnetism and show how the magnetic properties of a ferromagnetic layer stack can be manipulated directly by the electric-field oscillations of light, reducing the magnetic response time to an external stimulus by two orders of magnitude. To track the unfolding dynamics in real time, we develop an attosecond time-resolved magnetic circular dichroism detection scheme, revealing optically induced spin and orbital momentum transfer in synchrony with light-field-driven coherent charge relocation17. In tandem with ab initio quantum dynamical modelling, we show how this mechanism enables the simultaneous control of electronic and magnetic properties that are essential for spintronic functionality. Our study unveils light-field coherent control of spin dynamics and macroscopic magnetic moments in the initial non-dissipative temporal regime and establishes optical frequencies as the speed limit of future coherent spintronic applications, spin transistors and data storage media.

Construction of Hydration Layer for Proton Transport by Implanting the Hydrophilic Center Ag0 in Nickel Metal-Organic Frameworks.

The directional arrangement of H2O molecules can effectively regulate the ordered protons transfer to improve transport efficiency, which can be controlled by the interaction between materials and H2O. Herein, a strategy to build a stable hydration layer in metal-organic framework (MOF) platforms, in which hydrophilic centers that can manipulate H2O molecules are implanted into MOF cavities is presented. The rigid grid-Ni-MOF is selected as the supporting material due to the uniformly distributed cavities and rigid structures. The Ag0 possesses potential combination ability with the hydrophilic substances, so it is introduced into the MOF as hydration layer centers. Relying on the strong interaction between Ag0 and H2O, the H2O molecules can rearrange around Ag0 in the cavity, which is intuitively verified by DFT calculation and molecular dynamics simulation. The establishment of a hydration layer in Ag@Ni-MOF regulates the chemical properties of the material and gives the material excellent proton conduction performance, with a proton conductivity of 4.86 × 10-2 S cm-1.

Species pool, local assembly processes: Disentangling the mechanisms determining bacterial α- and ß-diversity during forest secondary succession.

Across ecology, and particularly within microbial ecology, there is limited understanding how the generation and maintenance of diversity. Although recent work has shown that both local assembly processes and species pools are important in structuring microbial communities, the relative contributions of these mechanisms remain an important question. Moreover, the roles of local assembly processes and species pools are drastically different when explicitly considering the potential for saturation or unsaturation, yet this issue is rarely addressed. Thus, we established a conceptual model that incorporated saturation theory into the microbiological domain to advance the understanding of mechanisms controlling soil bacterial diversity during forest secondary succession. Conceptual model hypotheses were tested by coupling soil bacterial diversity, local assembly processes and species pools using six different forest successional chronosequences distributed across multiple climate zones. Consistent with the unsaturated case proposed in our conceptual framework, we found that species pool consistently affected α-diversity, even while local assembly processes on local richness operate. In contrast, the effects of species pool on ß-diversity disappeared once local assembly processes were taken into account, and changes in environmental conditions during secondary succession led to shifts in ß-diversity through mediation of the strength of heterogeneous selection. Overall, this study represents one of the first to demonstrate that most local bacterial communities might be unsaturated, where the effect of species pool on α-diversity is robust to the consideration of multiple environmental influences, but ß-diversity is constrained by environmental selection.

HEAT SHOCK PROTEIN 90.6 interacts with carbon and nitrogen metabolism components during seed development.

Carbon and nitrogen are the two main nutrients in maize (Zea mays L.) kernels, and kernel filling and metabolism determine seed formation and germination. However, the molecular mechanisms underlying the relationship between kernel filling and corresponding carbon and nitrogen metabolism remain largely unknown. Here, we found that HEAT SHOCK PROTEIN 90.6 (HSP90.6) is involved in both seed filling and the metabolism processes of carbon and nitrogen. A single-amino acid mutation within the HATPase_c domain of HSP90.6 led to small kernels. Transcriptome profiling showed that the expression of amino acid biosynthesis- and carbon metabolism-related genes was significantly downregulated in the hsp90.6 mutant. Further molecular evidence showed strong interactions between HSP90.6 and the 26S proteasome subunits REGULATORY PARTICLE NON-ATPASE6 (RPN6) and PROTEASOME BETA SUBUNITD2 (PBD2). The mutation of hsp90.6 significantly reduced the activity of the 26S proteasome, resulting in the accumulation of ubiquitinated proteins and defects in nitrogen recycling. Moreover, we verified that HSP90.6 is involved in carbon metabolism through interacting with the 14-3-3 protein GENERAL REGULATORY FACTOR14-4 (GF14-4). Collectively, our findings revealed that HSP90.6 is involved in seed filling and development by interacting with the components controlling carbon and nitrogen metabolism.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury.

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.

Neutrophil Extracellular Traps Regulate Surgical Brain Injury by Activating the cGAS-STING Pathway.

Surgical brain injury (SBI), induced by neurosurgical procedures or instruments, has not attracted adequate attention. The pathophysiological process of SBI remains sparse compared to that of other central nervous system diseases thus far. Therefore, novel and effective therapies for SBI are urgently needed. In this study, we found that neutrophil extracellular traps (NETs) were present in the circulation and brain tissues of rats after SBI, which promoted neuroinflammation, cerebral edema, neuronal cell death, and aggravated neurological dysfunction. Inhibition of NETs formation by peptidylarginine deiminase (PAD) inhibitor or disruption of NETs with deoxyribonuclease I (DNase I) attenuated SBI-induced damages and improved the recovery of neurological function. We show that SBI triggered the activation of cyclic guanosine monophosphate-adenosine monophosphate synthase stimulator of interferon genes (cGAS-STING), and that inhibition of the cGAS-STING pathway could be beneficial. It is worth noting that DNase I markedly suppressed the activation of cGAS-STING, which was reversed by the cGAS product cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP, cGAMP). Furthermore, the neuroprotective effect of DNase I in SBI was also abolished by cGAMP. NETs may participate in the pathophysiological regulation of SBI by acting through the cGAS-STING pathway. We also found that high-dose vitamin C administration could effectively inhibit the formation of NETs post-SBI. Thus, targeting NETs may provide a novel therapeutic strategy for SBI treatment, and high-dose vitamin C intervention may be a promising translational therapy with an excellent safety profile and low cost.

Exploring the role of gut microbiota in migraine risk: a two-sample Mendelian randomization study.

OBJECTIVES: The presence of intestinal flora in the gut has been linked to migraines in recent studies, but whether the association is causal or due to bias remains to be clarified. We aimed to explore whether there is a potential causal relationship between gut microbiota and migraine risk with this study. MATERIALS AND METHODS: We conducted a two-sample Mendelian randomized analysis study to explore whether gut microbiota has a causal relationship with migraine using publicly available data from large-scale genome-wide association studies. The inverse variance weighting was used as the main method, and weighted median and MR-Egger were used as supplementary methods for causal inference. Sensitivity analyses, including leave-one-out analysis, Cochran Q test, and MR-Egger intercept test, were used to verify the robustness of the results. RESULTS: After rigorous quality control of the results, we identified that genetic predisposition towards a higher abundance of genus.Lactobacillus was causally associated with higher of migraine (IVW OR = 1.10, 95% CI = 1.03 - 1.18, p = .004), whereas the higher abundance of family.Prvotellaceae predicted a decreased risk of migraine (IVW OR = 0.89, 95% CI = 0.80 - 0.98, p = .02). Sensitivity analyses indicated the results were not biased by pleiotropy. CONCLUSION: According to our research, there is evidence showing that gut microbiota may be involved in migraine development, which suggested that a stool examination might be helpful to recognize those with a higher risk of migraine. Further mechanisms remained to be elucidated in future studies.

Third-Order Nonlinear Optical Modulation Behavior of Photoresponsive Bimetallic MOFs.

Bimetallic metal-organic frameworks (MOFs) capable of sensing external stimuli will provide more possibilities for further regulating third-order nonlinear optical (NLO) properties. In this work, we synthesized bimetallic MOFs (ZnCu-MOF and ZnCd-MOF) through central metal exchange using a photoresponsive Zn-MOF as a precursor. Compared with Zn-MOF, both ZnCu-MOF and ZnCd-MOF exhibit significantly enhanced third-order NLO absorption properties. This is mainly attributed to the introduction of metal ions with different electron configurations that can adjust the bandgap of MOFs and enhance electron delocalization, thus promoting electron transfer. Interestingly, the bimetallic MOFs show a transition from reverse saturation absorption (RSA) to saturation absorption (SA) after exposure to ultraviolet irradiation, as they retain the properties of directional photogenerated electron transfer. Photoresponsive bimetallic MOFs not only have the effect of bimetallic modulation of electronic structures but also have the characteristics of photoinduced electron transfer, exhibiting diversified optical properties. These findings provide a novel method for the development of multifunctional NLO materials.

Ingenious Modulation of Third-Order Nonlinear Optical Response of Zr-MOFs through Defect Engineering Based on a Mixed-Linker Strategy.

Defect engineering plays a pivotal role in regulating electronic structure and facilitating charge transfer, yielding captivating effects on third-order nonlinear optical (NLO) properties. In this work, we utilized a mixed-linker strategy to intentionally disrupt the initial periodic arrangement of UiO-66 and construct defects. Specifically, we incorporated tetrakis(4-carboxyphenyl)porphyrin (TCPP) with an exceptionally electron-rich delocalization system into the framework of UiO-66 using a one-pot solvothermal method, ingeniously occupying the partial distribution sites of the Zr6 clusters. Compared to UiO-66, the NLO absorption and refraction performance of TCPP/UiO-66 were significantly improved. Additionally, due to the presence of nitrogen-rich sites that can accommodate metal ions in the porphyrin ring of TCPP, Co(II), Ni(II), Cu(II), and Zn(II) are introduced into TCPP/UiO-66, extending the d-π conjugation effect to further regulate the defects. The NLO absorption behavior transforms saturation absorption (SA) to reverse saturation absorption (RSA), while the refraction behavior shifts from self-defocusing to self-focusing. This work shows that defects can effectively regulate the electronic structure, while TCPP plays a crucial role in significantly enhancing electron delocalization.