Optimizing soil conservation through comprehensive benefit assessment in river basins.

Land degradation from water erosion poses a significant threat to water security and ecosystem stability, driving global efforts in soil conservation. Quantitative assessment of soil conservation benefits-both on-site and off-site-is crucial for guiding effective conservation strategies. However, existing methodologies often fall short in quantifying the value of these combined benefits. Here, we present a comprehensive framework for quantifying soil conservation service flows in monetary terms, evaluating the effectiveness of both on-site and off-site measures. Applying this framework to the Yellow River Basin (YRB), we employ cost-avoidance algorithms related to soil fertility maintenance, dredging cost reduction, and mitigation of nonpoint source pollution. Our results reveal that while many areas contribute to both on-site and off-site benefits, over half of the YRB relies predominantly on off-site services. By strategically enhancing key regions-which constitute 30% of the basin-we demonstrate that the overall soil conservation service supply can increase by 64.2% over the multi-year average from 2001 to 2020 compared to a consideration of on-site only. These findings underscore the essential role of off-site services in fully understanding soil conservation needs, particularly in large river basins, and the identified priority areas can offer valuable insights for optimizing soil conservation efforts.

Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate muscle atrophy via the miR-132-3p/FoxO3 axis.

Background: Muscle atrophy or sarcopenia is the loss of muscle mass and strength and leads to an increased risk of disability and death including osteoporotic fractures. Currently, there are no available clinical biologic agents for the treatment of sarcopenia. Since exosomes have become increasingly attractive as a novel therapeutic approach due to their ability to facilitate cell-cell transfer of proteins and RNAs, promoting cell repair and function recovery, we hypothesized that human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) might benefit muscle atrophy in age-related and dexamethasone-induced sarcopenia animal models. Methods: HucMSC-Exos were harvested by ultrafast centrifugation and identified by transmission electron microscopy, particle size analysis, and Western blot analysis. The effects of hucMSC-Exos on muscle atrophy were evaluated using age-related and dexamethasone-induced muscle atrophy mice models. Body weight, grip strength, muscle weight, and muscle histology of these mice were assessed. The expression levels of muscle RING finger 1 (MuRF1) and muscle atrophy F-box (atrogin-1) were measured by Western blot. Dexamethasone-induced C2C12 myotube atrophy was used to establish the cell model of muscle atrophy. Myotube diameter was evaluated by immunofluorescence staining. Bioinformatic analysis, RNA sequencing analysis, and Western blot analysis were performed to explore the underlying mechanisms. Results: In vivo experiments, hucMSC-Exos demonstrated a remarkable capacity to improve grip strength, increase muscle mass, and muscle fiber cross-sectional area, while concurrently reducing the expression of MuRF1 and atrogin-1 in age-related and dexamethasone-induced muscle atrophy mice. In vitro experiments, hucMSC-Exos can promote the proliferation of C2C12 cells, and rescue the dexamethasone-induced decline in the viability of C2C12 myotubes. In addition, hucMSC-Exos can increase the diameter of C2C12 myotubes, and reduce dexamethasone-induced upregulation of MuRF1 and atrogin-1. Combined with bioinformatics analysis and RNA sequencing analysis, we further showed that miR-132-3p was one of the essential miRNAs in hucMSC-Exos and played an important role by targeting FoxO3. Conclusion: Our findings suggested that hucMSC-Exos can improve age-related and dexamethasone-induced muscle atrophy in mice models. This study first demonstrated that hucMSC-Exos may ameliorate muscle atrophy via the miR-132-3p/FoxO3 axis. These data may provide novel and valuable insights into the clinical transformation of hucMSC-Exos for the treatment of sarcopenia. The translational potential of this article: HucMSC-Exos are easily available for clinical application, this study further consolidates the evidence for the clinical transformation potential of hucMSC-Exos for sarcopenia and provides its new target pathway.

Genomic analysis and mechanisms exploration of a stress tolerance and high-yield pullulan producing strain.

Pullulan is a kind of natural polymer, which is widely used in medicine and food because of its solubility, plasticity, edible, non-toxicity and good biocompatibility. It is of great significance to improve the yield of pullulan by genetic modification of microorganisms. It was previously reported that Aureobasidium melanogenum TN3-1 isolated from honey-comb could produce high-yield of pullulan, but the molecular mechanisms of its production of pullulan had not been completely solved. In this study, the reported strains of Aureobasidium spp. were further compared and analyzed at genome level. It was found that genome duplication and genome genetic variations might be the crucial factors for the high yield of pullulan and stress resistance. This particular phenotype may be the result of adaptive evolution, which can adapt to its environment through genetic variation and adaptive selection. In addition, the TN3-1 strain has a large genome, and the special regulatory sequences of its specific genes and promoters may ensure a unique characteristics. This study is a supplement of the previous studies, and provides basic data for the research of microbial genome modification in food and healthcare applications.

A one-step protocol to generate impermeable fluorescent HaloTag substrates for in situ live cell application and super-resolution imaging.

Communication between cells is largely orchestrated by proteins on the cell surface, which allow information transfer across the cell membrane. Super-resolution and single-molecule visualization of these proteins can be achieved by genetically grafting HTP (HaloTag Protein) into the protein of interest followed by brief incubation of cells with a dye-HTL (dye-linked HaloTag Ligand). This approach allows for use of cutting-edge fluorophores optimized for specific optical techniques or a cell-impermeable dye-HTL to selectively label surface proteins without labeling intracellular copies. However, these two goals often conflict, as many high-performing dyes exhibit membrane permeability. Traditional methods to eliminate cell permeability face synthetic bottlenecks and risk altering photophysical properties. Here we report that dye-HTL reagents can be made cell-impermeable by inserting a charged sulfonate directly into the HTL, leaving the dye moiety unperturbed. This simple, one-step method requires no purification and is compatible with both the original HTL and second-generation HTL.2, the latter offering accelerated labeling. We validate such compounds, termed dye-SHTL ('dye shuttle') conjugates, in live cells via widefield microscopy, demonstrating exclusive membrane staining of extracellular HTP fusion proteins. In transduced primary hippocampal neurons, we label mGluR2, a neuromodulatory G protein-coupled receptor (GPCR), with dyes optimized for stimulated emission by depletion (STED) super-resolution microscopy, allowing unprecedented accuracy in distinguishing surface and receptors from those in internal compartments of the presynaptic terminal, important in neural communication. This approach offers broad utility for surface-specific protein labelling.

Exogenous Melatonin Reinforces Photosynthesis, Antioxidant Defense and Gene Expression to Ameliorate Na2CO3 Stress in Maize.

Salt stress can seriously affect the growth and development of maize (Zea mays L.), resulting in a great yield loss. Melatonin (MT), an indole hormone, is a potential enhancer of plant tolerance against salt stress. However, the complex mechanisms of MT application in enhancing maize salt tolerance are still unclear. Herein, three-leaf seedlings of salt-susceptible P138 and its salt-resistant ethyl methane sulfonate (EMS)-104 mutant were cultured with or without 150 µM MT application under 0 and 100 mM Na2CO3 treatments for seven days, to systematically explore the response mechanisms of exogenous MT in improving the salt tolerance of maize. The results showed that salt stress triggered an escalation in reactive oxygen species production, enhanced multiple antioxidant enzymes' activities, impaired cellular membrane permeability, inhibited photosynthetic pigment accumulation, and ultimately undermined the vigor and photosynthetic prowess of the seedlings. While suitable MT application counteracted the detrimental impacts of Na2CO3 on seedlings' growth and photosynthetic capacity, the seedling length and net photosynthetic rate of P138 and EMS-104 were increased by 5.5% and 18.7%, and 12.7% and 54.5%, respectively. Quantitative real-time PCR (qRT-PCR) analysis further showed that MT application activated the expression levels of antioxidant enzyme-related genes (Zm00001d025106, Zm00001d031908, Zm00001d027511, and Zm00001d040364) and pigment biosynthesis-related genes (Zm00001d011819 and Zm00001d017766) in both maize seedlings under Na2CO3 stress; they then formed a complex interaction network of gene expression, multiple physiological metabolisms, and phenotype changes to influence the salt tolerance of maize seedlings under MT or Na2CO3 stress. To sum up, these observations underscore that 150 µM MT can alleviate salt injury of maize seedlings, which may provide new insights for further investigating MT regulation mechanisms to enhance maize seedlings' salt resistance.

SpliceTransformer predicts tissue-specific splicing linked to human diseases.

We present SpliceTransformer (SpTransformer), a deep-learning framework that predicts tissue-specific RNA splicing alterations linked to human diseases based on genomic sequence. SpTransformer outperforms all previous methods on splicing prediction. Application to approximately 1.3 million genetic variants in the ClinVar database reveals that splicing alterations account for 60% of intronic and synonymous pathogenic mutations, and occur at different frequencies across tissue types. Importantly, tissue-specific splicing alterations match their clinical manifestations independent of gene expression variation. We validate the enrichment in three brain disease datasets involving over 164,000 individuals. Additionally, we identify single nucleotide variations that cause brain-specific splicing alterations, and find disease-associated genes harboring these single nucleotide variations with distinct expression patterns involved in diverse biological processes. Finally, SpTransformer analysis of whole exon sequencing data from blood samples of patients with diabetic nephropathy predicts kidney-specific RNA splicing alterations with 83% accuracy, demonstrating the potential to infer disease-causing tissue-specific splicing events. SpTransformer provides a powerful tool to guide biological and clinical interpretations of human diseases.

Maternal genetic variants in kinesin motor domains prematurely increase egg aneuploidy.

The female reproductive lifespan is highly dependent on egg quality, especially the presence of a normal number of chromosomes in an egg, known as euploidy. Mistakes in meiosis leading to egg aneuploidy are frequent in humans. Yet, knowledge of the precise genetic landscape that causes egg aneuploidy in women is limited, as phenotypic data on the frequency of human egg aneuploidy are difficult to obtain and therefore absent in public genetic datasets. Here, we identify genetic determinants of reproductive aging via egg aneuploidy in women using a biobank of individual maternal exomes linked with maternal age and embryonic aneuploidy data. Using the exome data, we identified 404 genes bearing variants enriched in individuals with pathologically elevated egg aneuploidy rates. Analysis of the gene ontology and protein-protein interaction network implicated genes encoding the kinesin protein family in egg aneuploidy. We interrogate the causal relationship of the human variants within candidate kinesin genes via experimental perturbations and demonstrate that motor domain variants increase aneuploidy in mouse oocytes. Finally, using a knock-in mouse model, we validate that a specific variant in kinesin KIF18A accelerates reproductive aging and diminishes fertility. These findings reveal additional functional mechanisms of reproductive aging and shed light on how genetic variation underlies individual heterogeneity in the female reproductive lifespan, which might be leveraged to predict reproductive longevity. Together, these results lay the groundwork for the noninvasive biomarkers for egg quality, a first step toward personalized fertility medicine.

Transcriptomic and Physiological Studies Unveil that Brassinolide Maintains the Balance of Maize's Multiple Metabolisms under Low-Temperature Stress.

Low-temperature (LT) is one of the major abiotic stresses that restrict the growth and development of maize seedlings. Brassinolides (BRs) have been shown to enhance LT tolerance in several plant species; the physiological and molecular mechanisms by which BRs enhance maize tolerance are still unclear. Here, we characterized changes in the physiology and transcriptome of N192 and Ji853 seedlings at the three-leaf stage with or without 2 µM 2,4-epibrassinolide (EBR) application at 25 and 15 °C environments via high-performance liquid chromatography and RNA-Sequencing. Physiological analyses revealed that EBR increased the antioxidant enzyme activities, enhanced the cell membrane stability, decreased the malondialdehyde formation, and inhibited the reactive oxygen species (ROS) accumulation in maize seedlings under 15 °C stress; meanwhile, EBR also maintained hormone balance by increasing indole-3-acetic acid and gibberellin 3 contents and decreasing the abscisic acid level under stress. Transcriptome analysis revealed 332 differentially expressed genes (DEGs) enriched in ROS homeostasis, plant hormone signal transduction, and the mitogen-activated protein kinase (MAPK) cascade. These DEGs exhibited synergistic and antagonistic interactions, forming a complex LT tolerance network in maize. Additionally, weighted gene co-expression network analysis (WGCNA) revealed that 109 hub genes involved in LT stress regulation pathways were discovered from the four modules with the highest correlation with target traits. In conclusion, our findings provide new insights into the molecular mechanisms of exogenous BRs in enhancing LT tolerance of maize at the seedling stage, thus opening up possibilities for a breeding program of maize tolerance to LT stress.

Exogenous Melatonin Alleviates NaCl Injury by Influencing Stomatal Morphology, Photosynthetic Performance, and Antioxidant Balance in Maize.

Maize (Zea mays L.) is sensitive to salt stress, especially during seed germination and seedling morphogenesis, which limits maize growth and productivity formation. As a novel recognized plant hormone, melatonin (MT) participates in multiple growth and developmental processes and mediates biotic/abiotic stress responses, yet the effects of salt stress on maize seedlings remain unclear. Herein, we investigated the effects of 150 µM exogenous MT on multiple phenotypes and physiologic metabolisms in three-leaf seedlings across eight maize inbred lines under 180 mM NaCl salt stress, including growth parameters, stomatal morphology, photosynthetic metabolisms, antioxidant enzyme activities, and reactive oxygen species (ROS). Meanwhile, the six gene expression levels controlling antioxidant enzyme activities and photosynthetic pigment biosynthesis in two materials with contrasting salt resistance were examined for all treatments to explore the possible molecular mechanism of exogenous MT alleviating salt injury in maize. The results showed that 150 µM exogenous MT application protected membrane integrity and reduced ROS accumulation by activating the antioxidant system in leaves of maize seedlings under salt stress, their relative conductivity and H2O2 level average reduced by 20.91% and 17.22%, while the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) averaged increased by 13.90%, 17.02%, 22.00%, and 14.24% relative to salt stress alone. The improvement of stomatal size and the deposition of photosynthetic pigments were more favorable to enhancing photosynthesis in leaves when these seedlings treated with MT application under salt stress, their stomatal size, chlorophyll content, and net photosynthetic rate averaged increased by 11.60%, 19.64%, and 27.62%. Additionally, Gene expression analysis showed that MT stimulation significantly increased the expression of antioxidant enzyme genes (Zm00001d009990, Zm00001d047479, Zm00001d014848, and Zm00001d007234) and photosynthetic pigment biosynthesis genes (Zm00001d011819 and Zm00001d017766) under salt stress. At the same time, 150 µM MT significantly promoted seedling growth and biomass accumulation. In conclusion, our study may unravel crucial evidence of the role of MT in maize seedlings against salt stress, which can provide a novel strategy for improving maize salt stress resistance.

Differential contribution of Arabidopsis chitin receptor complex components to defense signaling and ubiquitination-dependent endocytotic removal from the plasma membrane.

In Arabidopsis, the enzymatically active lysin motif-containing receptor-like kinase (LysM-RLK) CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) and the pseudokinases LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE 5 (LYK5) and LYK4 are the core components of the canonical chitin receptor complex. CERK1 dimerizes and autophosphorylates upon chitin binding, resulting in activation of chitin signaling. In this study, we clarified and further elucidated the individual contributions of LYK4 and LYK5 to chitin-dependent signaling using mutant (combination)s and stably transformed Arabidopsis plants expressing fluorescence-tagged LYK5 and LYK4 variants from their endogenous promoters. Our analyses revealed that LYK5 interacts with CERK1 upon chitin treatment, independently of LYK4 and vice versa. We show that chitin-induced autophosphorylation of CERK1 is predominantly dependent on LYK5, whereas chitin-triggered ROS generation is almost exclusively mediated by LYK4. This suggests specific signaling functions of these two co-receptor proteins apart from their redundant function in mitogen-activated protein kinase (MAPK) signaling and transcriptional reprogramming. Moreover, we demonstrate that LYK5 is subject to chitin-induced and CERK1-dependent ubiquitination, which serves as a signal for chitin-induced internalization of LYK5. Our experiments provide evidence that a combination of phosphorylation and ubiquitination events controls LYK5 removal from the plasma membrane via endocytosis, which likely contributes to receptor complex desensitization.

Bisphenol C Induces Cardiac Developmental Defects by Disrupting m6A Homeostasis.

Bisphenol A (BPA) is a commonly used plastic additive. Since BPA has been banned in maternal and infant food containers in many countries, BPA substitutes have been widely introduced to replace it. By systematically assessing the potential developmental toxicity of BPA substitutes, we observed that the 41-150 nM in vivo BPC exposure (around the reported concentration detected in infant urine: 6-186 nM) induced cardiac defects in zebrafish. Mechanistically, BPC disrupted m6A homeostasis by downregulation of the key m6A methyltransferase, Mettl3, thereby causing the m6A reader, Igf2bp2b, to fail in recognizing and stabilizing the inefficiently m6A-modified acox1 and tnnt2d mRNA. Then, downregulation of Acox1 (a regulator in cardiac fatty acid metabolism) and Tnnt2d (a component of cardiac troponin for muscle contraction) led to cardiac defects. Indeed, the dual cardiac functional axes regulated by the same m6A reader in response to BPC provided new insight into the regulatory mechanisms of epitranscriptomics and cardiac development. Collectively, our study not only presented evidence showing that the internal exposure levels of BPC in humans could lead to cardiac developmental defects but also demonstrated the underlying mechanism of BPC-mediated defects by disrupting the Mettl3-m6A-Igf2bp2b-Acox1/Tnnt2d pathways, which provided potential molecular markers associated with BPC exposure.

Fast, sensitive detection of protein homologs using deep dense retrieval.

The identification of protein homologs in large databases using conventional methods, such as protein sequence comparison, often misses remote homologs. Here, we offer an ultrafast, highly sensitive method, dense homolog retriever (DHR), for detecting homologs on the basis of a protein language model and dense retrieval techniques. Its dual-encoder architecture generates different embeddings for the same protein sequence and easily locates homologs by comparing these representations. Its alignment-free nature improves speed and the protein language model incorporates rich evolutionary and structural information within DHR embeddings. DHR achieves a >10% increase in sensitivity compared to previous methods and a >56% increase in sensitivity at the superfamily level for samples that are challenging to identify using alignment-based approaches. It is up to 22 times faster than traditional methods such as PSI-BLAST and DIAMOND and up to 28,700 times faster than HMMER. The new remote homologs exclusively found by DHR are useful for revealing connections between well-characterized proteins and improving our knowledge of protein evolution, structure and function.

Cross-scale coupling of ecosystem service flows and socio-ecological interactions in the Yellow River Basin.

As research on the full spectrum of ecosystem service (ES) generation and utilization within coupled human and natural systems (CHANS) has expanded, many studies have shown that the spatiotemporal dynamics of ESs are managed and influenced by human activities. However, there is insufficient research on how ESs are affected by bidirectional coupling between societal and ecological factors during spatial flow, particularly in terms of cross-scale impacts. These bidirectional influences between humans and nature are closely related to the utilization and transfer of ESs and affect the perception of spatiotemporal patterns of ESs and the formulation of management strategies. To fill this research gap, this study focuses on the Yellow River Basin (YRB), using network models to track the spatial dynamics of ES flows (ESFs) and the interactions between ecosystems and socio-economic systems within the basin on an annual scale from 2000 to 2020. The results highlight cross-scale impacts and feedback processes between local subbasins and the larger regional basin: As the supply-demand ratios of freshwater ESs, soil conservation ESs, and food ESs increase within individual subbasins of the YRB, more surplus ESs flow among subbasins. This not only alleviates spatial mismatches in ES supply and demand across the entire basin but also enhances the connectivity of the basin's ESF network. Subsequently, the cascading transfer and accumulation of ESs feedback into local socio-ecological interactions, with both socio-economic factors and the capacity for ES output within subbasins becoming increasingly reliant on external ES inflows. These results underscore the crucial role of ESFs within the CHANS of the YRB and imply the importance of cross-regional cooperation and cross-scale management strategies in optimizing ES supply-demand relationships. Furthermore, this study identifies the potential risks and challenges inherent in highly coupled systems. In conclusion, this work deepens the understanding of the spatial flow characteristics of ESs and their socio-ecological interactions; the analytical methods used in this study can also be applied to research on large river basins like the YRB, and even larger regional ecosystems.

Unveiling Nonsecular Collisional Dissipation of Molecular Alignment.

We conducted a joint theoretical and experimental study to investigate the collisional dissipation of molecular alignment. By comparing experimental measurements to the quantum simulations, the nonsecular effect in the collision dissipation of molecular alignment was unveiled from the gas-density-dependent decay rates of the molecular alignment revival signals. Different from the conventional perspective that the nonsecular collisional effect rapidly fades within the initial few picoseconds following laser excitation, our simulations of the time-dependent decoherence process demonstrated that this effect can last for tens of picoseconds in the low-pressure regime. This extended timescale allows for the distinct identification of the nonsecular effect from molecular alignment signals. Our findings present the pioneering evidence that nonsecular molecular collisional dissipation can endure over an extended temporal span, challenging established concepts and strengthening our understanding of molecular dynamics within dissipative environments.

In Situ Multi-Directional Liquid Manipulation Enabled by 3D Asymmetric Fang-Structured Surface.

Decorating surfaces with wetting gradients or topological structures is a prevailing strategy to control uni-directional spreading without energy input. However, current methods, limited by fixed design, cannot achieve multi-directional control of liquids, posing challenges to practical applications. Here, a structured surface composed of arrayed three-dimensional asymmetric fang-structured units is reported that enable in situ control of customized multi-directional spreading for different surface tension liquids, exhibiting five novel modes. This is attributed to bottom-up distributed multi-curvature features of surface units, which create varied Laplace pressure gradients to guide the spreading of different-wettability liquids along specific directions. The surface's capability to respond to liquid properties for multimodal control leads to innovative functions that are absent in conventional structured surfaces. Selective multi-path circuits can be constructed by taking advantage of rich liquid behaviors with the surface; surface tensions of wetting liquids can be portably indicated with a resolution scope of 0.3-3.4 mN m-1 using the surface; temperature-mediated change of liquid properties is utilized to smartly manipulate liquid behavior and achieve the spatiotemporal-controllable targeted cooling of the surface at its heated state. These novel applications open new avenues for developing advanced surfaces for liquid manipulation.

Benzoxazinoids Biosynthetic Gene Cluster Identification and Expression Analysis in Maize under Biotic and Abiotic Stresses.

Benzoxazinoids (BXs) are unique bioactive metabolites with protective and allelopathic properties in maize in response to diverse stresses. The production of BXs involves the fine regulations of BXs biosynthetic gene cluster (BGC). However, little is known about whether and how the expression pattern of BGC members is impacted by biotic and abiotic stresses. Here, maize BGC was systemically investigated and 26 BGC gene members were identified on seven chromosomes, for which Bin 4.00-4.01/4.03-4.04/7.02 were the most enriched regions. All BX proteins were clearly divided into three classes and seven subclasses, and ten conserved motifs were further identified among these proteins. These proteins were localized in the subcellular compartments of chloroplast, endoplasmic reticulum, or cytoplasmic, where their catalytic activities were specifically executed. Three independent RNA-sequencing (RNA-Seq) analyses revealed that the expression profiles of the majority of BGC gene members were distinctly affected by multiple treatments, including light spectral quality, low-temperature, 24-epibrassinolide induction, and Asian corn borer infestation. Thirteen differentially expressed genes (DEGs) with high and specific expression levels were commonly detected among three RNA-Seq, as core conserved BGC members for regulating BXs biosynthesis under multiple abiotic/biotic stimulates. Moreover, the quantitative real-time PCR (qRT-PCR) verified that six core conserved genes in BGC were significantly differentially expressed in leaves of seedlings upon four treatments, which caused significant increases in 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) content under darkness and wound treatments, whereas a clear decrease in DIMBOA content was observed under low-temperature treatment. In conclusion, the changes in BX metabolites in maize were regulated by BGC gene members in multiple stress presences. Therefore, the identification of key genes associated with BX accumulation under biotic/abiotic stresses will provide valuable gene resources for breeding maize varieties with enhanced capability to adapt to environmental stresses.

Maternal genetic variants in kinesin motor domains prematurely increase egg aneuploidy.

The female reproductive lifespan depends on egg quality, particularly euploidy. Mistakes in meiosis leading to egg aneuploidy are common, but the genetic landscape causing this is not well understood due to limited phenotypic data. We identify genetic determinants of reproductive aging via egg aneuploidy using a biobank of maternal exomes linked with maternal age and embryonic aneuploidy data. We found 404 genes with variants enriched in individuals with high egg aneuploidy rates and implicate kinesin protein family genes in aneuploidy risk. Experimental perturbations showed that motor domain variants in these genes increase aneuploidy in mouse oocytes. A knock-in mouse model validated that a specific variant in kinesin KIF18A accelerates reproductive aging and diminishes fertility. These findings suggest potential non-invasive biomarkers for egg quality, aiding personalized fertility medicine. One sentence summary: The study identifies novel genetic determinants of reproductive aging linked to egg aneuploidy by analyzing maternal exomes and demonstrates that variants in kinesin genes, specifically KIF18A , contribute to increased aneuploidy and accelerated reproductive aging, offering potential for personalized fertility medicine.

Ultrafast Picometer-Resolved Molecular Structure Imaging by Laser-Induced High-Order Harmonics.

Real-time visualization of molecular transformations is a captivating yet challenging frontier of ultrafast optical science and physical chemistry. While ultrafast x-ray and electron diffraction methods can achieve the needed subangstrom spatial resolution, their temporal resolution is still limited to hundreds of femtoseconds, much longer than the few femtoseconds required to probe real-time molecular dynamics. Here, we show that high-order harmonics generated by intense femtosecond lasers can be used to image molecules with few-ten-attosecond temporal resolution and few-picometer spatial resolution. This is achieved by exploiting the sensitive dependence of molecular recombination dipole moment to the geometry of the molecule at the time of harmonic emission. In a proof-of-principle experiment, we have applied this high-harmonic structure imaging (HHSI) method to monitor the structural rearrangement in NH_{3}, ND_{3}, and N_{2} from one to a few femtoseconds after the molecule is ionized by an intense laser. Our findings establish HHSI as an effective approach to resolve molecular dynamics with unprecedented spatiotemporal resolution, which can be extended to trace photochemical reactions in the future.

Accurate prediction of antibody function and structure using bio-inspired antibody language model.

In recent decades, antibodies have emerged as indispensable therapeutics for combating diseases, particularly viral infections. However, their development has been hindered by limited structural information and labor-intensive engineering processes. Fortunately, significant advancements in deep learning methods have facilitated the precise prediction of protein structure and function by leveraging co-evolution information from homologous proteins. Despite these advances, predicting the conformation of antibodies remains challenging due to their unique evolution and the high flexibility of their antigen-binding regions. Here, to address this challenge, we present the Bio-inspired Antibody Language Model (BALM). This model is trained on a vast dataset comprising 336 million 40% nonredundant unlabeled antibody sequences, capturing both unique and conserved properties specific to antibodies. Notably, BALM showcases exceptional performance across four antigen-binding prediction tasks. Moreover, we introduce BALMFold, an end-to-end method derived from BALM, capable of swiftly predicting full atomic antibody structures from individual sequences. Remarkably, BALMFold outperforms those well-established methods like AlphaFold2, IgFold, ESMFold and OmegaFold in the antibody benchmark, demonstrating significant potential to advance innovative engineering and streamline therapeutic antibody development by reducing the need for unnecessary trials. The BALMFold structure prediction server is freely available at https://beamlab-sh.com/models/BALMFold.

miR-144 affects the immune response and activation of inflammatory responses in Cynoglossus semilaevis by regulating the expression of CsMAPK6.

MicroRNAs are increasingly recognized for their pivotal role in the immune system, yet the specific regulatory functions of fish-derived microRNAs remain largely unexplored. In this research, we discovered a novel miRNA, Cse-miR-144, in the Chinese tongue sole (Cynoglossus semilaevis), characterized by a 73-base pair precursor and a 21-nucleotide mature sequence. Our findings revealed that the expression of Cse-miR-144 was notably inhibited by various Vibrio species. Utilizing bioinformatics and dual-luciferase assay techniques, we established that the pro-inflammatory cytokine gene CsMAPK6 is a direct target of Cse-miR-144. Subsequent in vitro and in vivo western blotting analyses confirmed that Cse-miR-144 can effectively reduce the protein levels of CsMAPK6 post-transcriptionally. Moreover, CsMAPK6 is known to be involved in the activation of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB). Additional investigations using qPCR and ELISA demonstrated that suppression of Cse-miR-144 leads to an upsurge in the liver mRNA levels of various immune genes (including MYD88, TRAF6, NF-κB, TRAF2, TRAF3, and TNF), alongside a marked increase in the production and secretion of pro-inflammatory cytokines (IL-1ß, IL-6, and IL-8) in the bloodstream of C. semilaevis. These findings collectively underscore the potential of Cse-miR-144 as a key inhibitor of CsMAPK and its crucial role in modulating the immune and inflammatory responses in teleost fish. Compared to the siRNA, miRNA is a better tool in controlling the expression of target gene with a lower cost.