Biology subjects

Ding, N.

Publications and source records attributed to Ding, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Plantaricin JK from Lactiplantibacillus plantarum ZJ316 inhibits enterohemorrhagic Escherichia coli O104:H4 and alters fecal microbial communities in vitro

Enterohemorrhagic Escherichia coli (EHEC) O104:H4 is a highly virulent foodborne pathogen for which antibiotic therapy is contraindicated, severely restricting conventional treatment options; therefore, the development of novel antimicrobial strategies is essential. This study investigated the antibacterial activity and gut microbiota-modulating effects of plantaricin JK (PlnJK), a two-peptide bacteriocin from Lactiplantibacillus plantarum. Chemically synthesized PlnJK exhibited a minimum inhibitory concentration (MIC) of 32 M against E. coli O104:H4, disrupting membrane integrity as evidenced by increased extracellular conductivity, ATP depletion, and ultrastructural damage. In an in vitro fecal fermentation model, PlnJK reduced Escherichia-Shigella abundance from 36.70% to 30.60% which contains E. coli O104:H4-related taxa, enriched Clostridium (5.70% vs 2.40% in infection group), Rikenellaceae, and Lactobacillaceae, and significantly elevated short-chain fatty acid (SCFA) levels including butyrate (p < 0.01) and isovalerate (p < 0.05). To translate this into a deliverable format, CRISPR-Cas9-engineered L. plantarum strains with plnJK knockout, complementation, and overexpression were constructed. Compared with the chemically synthesized peptide, LAB-derived PlnJK--especially from the overexpression strain--showed superior efficacy in restoring microbial diversity and enhancing SCFA production, significantly increased Shannon index and reduced dominance (p < 0.01), while promoting butyrate (p < 0.01) and isovalerate (p < 0.01) production compared to the knockout control. The engineered strains further revealed a clear dose-dependent effect, as overexpression potentiated while knockout abolished the beneficial modulation. These findings demonstrate that PlnJK acts through membrane disruption and beneficially modulates gut microecology, with LAB-mediated in situ delivery offering a promising strategy for anti-EHEC live biotherapeutic development.

microbiology↗

bioRxiv2026

Epithelial Self-Organization Patterns the Tadpole Oral Disc

Vertebrate epidermal organs are generally patterned through epithelial-mesenchymal interactions, but whether such interactions are essential for all epidermal organs remains unclear. Here we show that the elaborate oral disc of anuran tadpoles arises by partitioning a continuous oral epithelium into developmentally distinct jaw, tooth-row and papilla modules, in the absence of a mesenchymal organizer. Spatially restricted epithelial programs specify, maintain and differentiate these modules, enabling their semi-independent development. Perturbation of lef1, hoxc13, sox7 and pitx2 selectively disrupts individual modules. The resulting module-specific reductions, expansions and rearrangements mirror oral-disc configurations that have evolves repeatedly across anurans. These findings indicate that differential deployment of shared epithelial programs can generates selectable variation in the tadpole oral disc, allowing transient larval feeding structures to diversify independently of adult ecology and enabling tadpoles to exploit diverse ecological niches. Epidermal self-organization can therefore generate structural complexity, promote functional diversification and enhance evolvability in transient vertebrate organs.

developmental biology↗

bioRxiv2026

NeuralRNN: a unified framework for recurrent neural network methods in cognitive neuroscience

Recurrent neural networks (RNNs) provide a central tool in neuroscience to optimize cognitive tasks and reconstruct dynamical systems. Around these two paradigms, many RNN model variants have been tailored to capture specific computations of the brain. In practice, however, this methodological diversity remains difficult to exploit, because different paradigms and model variants are mostly implemented in idiosyncratic, study-specific code. Here we introduce NeuralRNN, an open-source Python framework that unifies these paradigms and model variants in a general-purpose pipeline. NeuralRNN brings task optimization, dynamical system reconstruction, and biological constraints into a single objective interface. It also provides an integrated and extensible model library spanning generic, structure-constrained, gain-modulated, and gated RNNs. Furthermore, data, models, and training are constructed through a shared automated pipeline and are equipped with a suite of tools for dynamical systems analysis. Together, NeuralRNN lowers the barrier to implementing, comparing, and extending RNN methods in neuroscience.

neuroscience↗

bioRxiv2026

Speech and music exploit distinct intrinsic timescales of the sensorimotor system

Humans produce a remarkable diversity of vocal behaviors throughout life, from innate sounds such as cry, laughter, and babble to learned, sophisticated sequences such as speech and song. Whether these diverse vocalizations share basic principles in their temporal organization remains unknown. Here, we show that, despite their distinct functions and extraordinary cultural variation, these vocalizations consistently occupy two characteristic rhythmic regimes supporting distinct functionalities. Corpus analyses revealed that, by approximately three years of age, the acoustic rhythms of speech and song settle into two distinct frequency ranges: one between 4 and 8Hz, the other below 2Hz. Critically, these two temporal regimes are already evident in infant cry, laughter, and babble, prior to the emergence of language and song. Sensorimotor synchronization experiments, where participants vocalized or tapped to sound sequences presented at different rates, revealed that individual vocal production exhibited maximal resonance between 4 and 8Hz, whereas synchronization across individuals was strongest below 2Hz. Together, these findings identify two functionally distinct sensorimotor timescales that organize diverse human vocal behavior: a faster timescale supporting stable individual vocal production and a slower timescale facilitating interpersonal synchronization.

animal behavior and cognition↗

bioRxiv2026

Efficient neural encoding of time intervals in speech and complex sound sequences

Encoding time intervals in complex sound faces dual challenges: it must be precise and cover a broad dynamic range. In speech, for example, a ten millisecond lengthening of a syllable can signal stress or phrasal boundaries, yet the syllable duration distribution is long tailed beyond 500 ms and has variable statistics across speakers. Here, we propose that the auditory cortex employs efficient coding to represent time intervals. When listeners heard syllable sequences drawn from different duration distributions, the magnetoencephalographic (MEG) response from the temporal cortex scaled with syllable duration, which is characterized using the interval-response function. Crucially, this interval-response function met predictions of efficient coding. Its intercept and slope adapted to the mean and variance of syllable duration, respectively, and it consistently exhibited a compressive nonlinearity that reduced response skewness, consistent with a maximum-entropy code. A computational model that constantly updates the inference of duration distribution provided an algorithmic account of this efficient coding, and intracranial electroencephalogram (iEEG) data confirmed the same principles during natural speech comprehension. Together, our findings reveal an efficient neural mechanism that supports precise encoding of highly variable time intervals in complex sound sequences.

neuroscience↗

bioRxiv2026

SRC Knockdown Impairs Proliferation, Migration, and Invasion While Promoting Apoptosis in HTR8/SVneo Trophoblast Cells via Activation of the PI3K/Akt/Bcl-2 Signaling Pathway

SRC knockdown inhibits trophoblast cell proliferation, migration, and invasion while inducing apoptosis via activation of the PI3K/Akt/Bcl-2 signaling pathway. Trophoblast dysfunction is central to pregnancy disorders such as preeclampsia and miscarriage, yet the role of SRC, a non-receptor tyrosine kinase, in these cells remains poorly understood. This study aimed to elucidate the functional impact of SRC on trophoblast behavior and its underlying mechanism. Using siRNA-mediated knockdown in HTR8/SVneo cells, we confirmed efficient reduction of SRC mRNA and protein expression via RT-qPCR and Western blot. Functional assays demonstrated that SRC silencing significantly suppressed cell proliferation (CCK-8), migration (wound healing), and invasion (Transwell), while promoting apoptosis, evidenced by increased Annexin V-FITC/PI staining and upregulated Caspase-3 and Caspase-9 protein levels. Mechanistically, Western blot analysis revealed that SRC knockdown upregulated PI3K, Akt1, and Bcl-2 protein expression without altering IRS1 levels, indicating activation of the PI3K/Akt/Bcl-2 pro-survival pathway. This paradoxical activation appears to be a compensatory feedback insufficient to overcome SRC loss-induced dysfunction. Our findings identify SRC as a critical positive regulator of trophoblast proliferation, motility, and survival, acting through a non-canonical, IRS1-independent negative regulation of PI3K/Akt signaling. This study provides novel insights into trophoblast biology and suggests SRC as a potential therapeutic target for pregnancy complications; future in vivo studies are warranted to validate these mechanisms.

molecular biology↗

bioRxiv2026

miR-6818-5p Drives Ovarian Granulosa Cell Dysfunction in PCOS via Targeting HSD17B2 and Modulating PI3K/Caspase-9 Axis

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries, with granulosa cell dysfunction being a key pathological feature. This study aimed to investigate the role of microRNA-6818-5p in PCOS pathogenesis. Quantitative PCR revealed a significant upregulation of circulating miR-6818-5p in PCOS patients compared to healthy controls. In vitro, functional assays in the human granulosa cell line KGN demonstrated that miR-6818-5p overexpression markedly inhibited cell proliferation (assessed by CCK-8 assay) and promoted apoptosis (measured by Annexin V/PI flow cytometry). Mechanistically, dual-luciferase reporter assay and Western blotting identified HSD17B2 as a direct target of miR-6818-5p, with miR-6818-5p mimics significantly suppressing HSD17B2 protein expression. In conclusion, our findings reveal that elevated miR-6818-5p in PCOS may contribute to follicular development dysfunction by targeting HSD17B2 to disrupt granulosa cell proliferation and apoptosis balance, offering novel insights into PCOS pathology and highlighting miR-6818-5p as a potential diagnostic biomarker and therapeutic target.

molecular biology↗

bioRxiv2026

Real-Time Cell Analysis Reveals Distinct Roles of S100A4 in Regulating Proliferation, Migration, and Invasion of JAR Choriocarcinoma Cells

S100A4, a metastasis promoting calcium binding protein, drives tumor progression through pleiotropic mechanisms, yet its context dependent functions in gestational malignancies remain elusive. To dynamically decode its role in choriocarcinoma pathogenesis, we leveraged label free real time cell analysis (RTCA) to profile malignant phenotypes in JAR cells following siRNA mediated S100A4 silencing, complemented by apoptosis assessment and targeted signaling profiling. Efficient knockdown (verified by qPCR/Western blotting) significantly attenuated cellular proliferation (96 hr cell index slope decreased vs. scramble control; p<0.01) and suppressed migration capacity (p<0.01). Critically, S100A4 depletion did not induce apoptosis (flow cytometry and cleaved caspase 3/9 blotting confirmed no significant change), and invasion through Matrigel coated membranes remained statistically unaltered despite comparable experimental rigor. Mechanistically, S100A4 silencing triggered adaptive signaling rewiring: IRS1 and PI3K expression were elevated, Akt1 was suppressed, while MEK1/2 remained unchanged suggesting compensatory pathway activation.

cell biology↗

bioRxiv2025

Fos labels a distinct excitatory neuron ensemble for memory retrieval

Experience-triggered expression of Fos has been extensively used as a marker representing memory engram. It is generally assumed that Fos-positive neurons are preferentially excited by the experience, yet this has not been directly examined. In this study, we tracked neuron activity and Fos expression in somatosensory cortex and dentate gyrus of hippocampus in mice, during electric shock-induced fear memory formation and retrieval. Contrary to the prevailing view, we found that calcium features fail to predict Fos for individual cells. Fos-positive neurons show no specific activation to stimuli during memory encoding, but their activities become stimuli-selective during retrieval. Surprisingly, inhibiting neurons that will express Fos during encoding does not affect the induction of memory-guided behavior upon their activation. Network simulation and voltage imaging further showed that connectivity to interneurons, not stimulus responsiveness, is a major factor determining Fos expression. Our results indicate that Fos labels excitatory neurons specific for memory retrieval.

neuroscience↗

bioRxiv2024

Convincing Evidence of Carnivorous Diet in Alvarezsaurian Dinosaur

A dietary shift from carnivory to insectivore has been proposed to explain the dramatic morphological evolution of alvarezsaurians, particularly the adaptation related to the manual digital reduction and body size miniaturization. However, based solely on morphological shifts, this hypothesis lacked direct dietary evidence to support either carnivory or insectivore. Here, we present the first convincing dietary evidence for alvarezsaurians, derived from the intestinal contents of the Early Cretaceous Bannykus wulatensis. Our analysis revealed significantly higher levels of calcium and phosphorus in the intestinal contents compared to the surrounding sandstone. Scanning electron microscopy identified hard tissue debris and possible soft tissues surrounding by phosphatized bacteria and tightly packed hollow microspheres, suggesting that the intestinal contents were strongly pseudomorphed by phosphatized microbes during fossilization. Raman spectroscopy showed characteristic peaks indicative of bone-derived material, consistent with the hard tissue debris appeared in the intestinal contents. Our results suggest that Bannykus had a carnivorous diet with strong chemical digestion, which likely compensated for its delicate cranial structures and small teeth. These results imply that if a dietary shift to insectivore occurred, it likely took place later in alvarezsaurian evolution, probably coinciding with a reduction in body size.

paleontology↗

bioRxiv2024

Low-frequency Cortical Activity Reflects Context-dependent Parsing of Word Sequences

During speech listening, it has been hypothesized that the brain builds representations of large linguistic structures such as sentences, which are captured by neural activity tracking the rhythm of these structures. Nevertheless, it has been concerned that the brain may only encode words, and neural activity tracking structures may be confounded by neural activity tracking the predictability or syntactic properties of individual words. Here, to disentangle the neural responses to sentences and words, we design word sequences that are parsed into different sentences in different contexts. By analyzing neural activity recorded by magnetoencephalography, we find that low-frequency neural activity strongly depends on the context - The difference between MEG responses to the same word sequence in two contexts yields a low-frequency signal, most strongly generated in the superior temporal gyrus, which precisely tracks sentences. The predictability and syntactic properties of words can partly explain the neural response in each context but cannot explain the difference between contexts. In summary, low-frequency neural activity encodes sentences and can reliably reflect how the same word sequence is parsed in different contexts.

neuroscience↗

bioRxiv2024

Cortical connectivity supports motoric synchronization to both auditory and visual rhythms in a frontal-temporal network

Synchronizing motoric responses to metrical sensory rhythms is key to social activities, e.g., group singing and dancing. It remains elusive, however, whether there is a common neural network for motoric synchronization to metrical rhythms from different sensory modalities. Here, we separate sensorimotor responses from basic sensory responses by combining a metrical sensorimotor synchronization task with frequency-domain magnetoencephalography (MEG) analysis. A common frontal-temporal network, not including visual cortex, is observed during both visual- and auditory-motor synchronization, and the network remains in congenitally deaf participants during visual-motor synchronization, suggesting the network is formed by intrinsic cortical connections instead of auditory experience. Furthermore, activation of the left and right frontal-temporal areas, as well as the ipsilateral white matter connection, separately predict the precision of auditory and visual synchronization. These results reveal a common but lateralized frontal-temporal network for visual- and auditory-motor synchronization, which is generated based on intrinsic cortical connections.

neuroscience↗

bioRxiv2024

2-D Neural Geometry Underpins Hierarchical Organization of Sequence in Human Working Memory

Working memory (WM) is constructive in nature. Instead of passively retaining information, WM reorganizes complex sequences into hierarchically embedded chunks to overcome capacity limits and facilitate flexible behavior. To investigate the neural mechanisms underlying hierarchical reorganization in WM, we performed two electroencephalography (EEG) and one magnetoencephalography (MEG) experiments, wherein humans retain in WM a temporal sequence of items, i.e., syllables, which are organized into chunks, i.e., multisyllabic words. We demonstrate that the 1-D sequence is represented by 2-D neural representational geometry in WM arising from parietal-frontal regions, with separate dimensions encoding item position within a chunk and chunk position in the sequence. Critically, this 2-D geometry is observed consistently in different experimental settings, even during tasks discouraging hierarchical reorganization in WM and correlates with WM behavior. Overall, these findings strongly support that complex sequences are reorganized into factorized multi-dimensional neural representational geometry in WM, which also speaks to general structure-based organizational principles given WMs involvement in many cognitive functions.

neuroscience↗

bioRxiv2024

Human Motor Cortex Encodes Complex Handwriting Through a Sequence of Primitive Neural States

How the human motor cortex (MC) orchestrates sophisticated fine movements such as handwriting remains a puzzle1-3. Here, we investigate this question through Utah array recordings from human MC hand knob, during imagined handwriting of Chinese characters (306 characters tested, 6.3 {+/-} 2.0 strokes per character). We find MC programs the writing of complicated characters by sequencing a small set of primitive states: The directional tuning of motor neurons remains stable within each primitive state but strongly varies across states. Furthermore, the occurrence of a primitive state is encoded by a separate set of neurons not directly involved in movement control. By automatically identifying the primitive states and corresponding neuronal tuning properties, we can reconstruct a recognizable writing trajectory for each character (84% improvement in reconstruction accuracy compared with baseline). Our findings unveil that skilled, sophisticated movements are decomposed into a sequence of primitive movements that are programmed through state-specific neural configurations, and this hierarchical control mechanism sheds new light on the design of high-performance brain-computer interfaces.

neuroscience↗

bioRxiv2024

A conserved Pol II elongator SPT6L mediates Pol V transcription elongation to regulate RNA-directed DNA methylation in Arabidopsis

In plants, the plant-specific RNA polymerase V (Pol V) transcripts non-coding RNAs and provides a docking platform for the association of accessory proteins in the RNA-directed DNA methylation (RdDM) pathway. Various components have been uncovered that are involved in the process of DNA methylation, but it is still not clear how the transcription of Pol V is regulated. Here, we found that the conserved Pol II elongator, SPT6L, bound to thousands of intergenic regions in an RNA polymerase II (Pol II) independent manner. The intergenic enrichment of SPT6L, interestingly, co-occupied with the largest subunit of Pol V (NRPE1) and mutation of SPT6L led to the reduction of DNA methylation but not Pol V enrichment. Furthermore, the association of SPT6L at Pol V loci was dependent on the Pol V associated factor, SPT5L, rather than the presence of Pol V, and the interaction between SPT6L and NRPE1 was compromised in spt5l. Finally, Pol V RIP-seq revealed that SPT6L is required to maintain the amount and length of Pol V transcripts. Our findings thus uncovered the critical role of a Pol II conserved elongator in Pol V mediated DNA methylation and transcription, and shed light on the mutual regulation between Pol V and II in plants.

plant biology↗

bioRxiv2023

Selective inhibition of interleukin-2 inducible T cell kinase (ITK) enhances anti-tumor immunity in association with Th1-skewing, cytotoxic T cell activation, and reduced T cell exhaustion

ITK is a tyrosine kinase expressed predominantly by T lymphocytes. In mice, selective knock-out of the ITK gene produces Th1 skewing of T helper cell differentiation. We synthesized a covalent ITK inhibitor, soquelitinib, that binds ITK with greater than 100-fold selectivity compared to binding to resting lymphocyte kinase (RLK). In vitro studies with normal or malignant T cells demonstrated that soquelitinib suppresses Th2 cytokine production preferentially with relative sparing of Th1 cytokines. Soquelitinib inhibits the in vivo growth of several syngeneic murine tumors including those that do not express ITK. Treatment with soquelitinib leads to increased tumor infiltration of normal CD8+ cells that possess enhanced T effector function. Soquelitinib inhibited expression of T cell exhaustion markers and was able to restore T effector function to exhausted cells. Pharmacologic selective ITK inhibition may represent a novel approach to cancer immunotherapy.

cancer biology↗

bioRxiv2023

Automatic Auditory Streaming Restores Missing Temporal Modulations in Echoic Speech

Human listeners can reliably recognize speech in adverse listening environments, and previous studies have identified that reliable neural encoding of slow temporal modulations in speech is essential for speech recognition. Recent behavioral studies demonstrate that long-delay echoes, which are rare in physical environments but common during online conferencing, can eliminate critical temporal modulations. These echoes, however, barely affect speech intelligibility, and here we investigate the underlying neural mechanisms. MEG experiments demonstrate that cortical activity can effectively track the temporal modulations eliminated by an echo, which cannot be explained by basic neural adaptation mechanisms such as synaptic depression, gain control, and adaptive filtering. Instead, the cortical response to echoic speech is better explained by a model that segregates speech from its echo than a model that encodes echoic speech as a whole. The speech segregation effect is observed even when attention is diverted, but disappears when speech segregation cues in the spectro-temporal fine structure are degraded. Altogether, these results strongly suggest that the auditory system can automatically segregate speech and its echo and encode them as two auditory streams, providing a potential neural basis for reliable speech recognition in echoic environments.

neuroscience↗

bioRxiv2023

Human Attention during Goal-directed Reading Comprehension Relies on Task Optimization

The computational principles underlying attention allocation in complex goal-directed tasks remain elusive. Goal-directed reading, i.e., reading a passage to answer a question in mind, is a common real-world task that strongly engages attention. Here, we investigate what computational models can explain attention distribution in this complex task. We show that the reading time on each word is predicted by the attention weights in transformer-based deep neural networks (DNNs) optimized to perform the same reading task. Eye-tracking further reveals that readers separately attend to basic text features and question-relevant information during first-pass reading and rereading, respectively. Similarly, text features and question relevance separately modulate attention weights in shallow and deep DNN layers. Furthermore, when readers scan a passage without a question in mind, their reading time is predicted by DNNs optimized for a word prediction task. Therefore, we offer a computational account of how task optimization modulates attention distribution during real-world reading.

neuroscience↗