Biology subjects

Yong, Y.

Publications and source records attributed to Yong, Y..

9 recordsLinked to original sources

bioRxiv2026

Resilience to neuronal hyperactivity and restoration of the neuroimmune interactome by blocking fibrin-induced microglia activation in Alzheimers disease

Cerebrovascular pathology and neuronal network dysfunction are early features of Alzheimers disease (AD) associated with neuroinflammation and cognitive decline, but the vascular and immune triggers of neuronal hyperactivity remain largely unknown. Here, we show that the blood coagulation protein fibrin disrupts microglia-neuron interactions, promoting neuronal hyperactivity in an AD mouse model. Genetic elimination of the fibrin inflammatory domain reduced neuronal hyperactivity, restored dynamic microglial interactions with active neurons and protected from high-risk decision making in 5XFAD mice. Leveraging the transcriptional signatures of microglia and inhibitory and excitatory neurons, a ligand-receptor atlas revealed fibrin-dependent disruption of innate immune and glutamatergic signaling between microglia and neurons in AD mice. Patients with AD also showed a correlation of cerebrospinal fluid (CSF) fibrinogen levels with biomarkers of inflammation, vascular and synaptic dysfunction. Thus, resilience to neuronal hyperactivity and restoration of the neuroimmune interactome by targeting fibrin may have therapeutic implications for Alzheimers disease and related conditions. There is a companion manuscript submitted to bioRxiv (Lauderdale et al., 2026) HighlightsO_LIVascular-microglia axis drives neuronal hyperactivity C_LIO_LIFibrin inflammatory activity disrupts the microglia-neuron interactome C_LIO_LIMicroglia activation by fibrin impairs decision-making in AD mice C_LIO_LISynaptic dysfunction and immune biomarkers correlate with CSF fibrinogen in AD patients C_LI

neuroscience↗

bioRxiv2026

Chromosome-level genome assembly of macroalgae Gracilariopsis lemaneiformis

As an important cultivated red alga, Gracilariopsis lemaneiformis has great economic and ecological value. However, its existing genome assembly is highly fragmented and inadequately annotated. In this study, we constructed the first high-quality chromosome-level genome of Gp. lemaneiformis using PacBio long reads, Illumina short reads and Hi-C sequencing data. The assembled genome was approximately 86.66 Mb and the assembled sequences were anchored to 28 pseudo-chromosomes with lengths ranging from 1.70 to 7.81 Mb. 99.91% of the PacBio reads could be mapped to our assembly. In total, 8,664 genes were annotated, and the repeat elements identified in Gp. lemaneiformis constituted 65.04% of the whole genome, including 2.24% tandem repeat sequences and 62.81% interspersed repeats. We also established a high-evidence phylogenetic tree from 19 representative algae species, with the main aim to calculate their divergence times. This high-quality genome of Gp. lemaneiformis provides a crucial foundation for understanding genetic characteristics, investigating the genomic evolution, and facilitating molecular breeding.

genomics↗

bioRxiv2025

Ultrasonic Modulation of Astrocytic and Neuronal Calcium Dynamics in Mouse Cortex

BackgroundAstrocytes are abundant in the brain and their calcium signaling is reported to have an important effect on neuronal activity in both physiological and pathological conditions. Low-frequency focused ultrasound (FUS) has recently emerged as a powerful noninvasive neuromodulation approach, yet its impact on astrocyte calcium dynamics in different brain states in vivo is poorly understood. ObjectiveThis study aimed to elucidate the effects of non-thermal FUS on astrocyte calcium dynamic with in vivo cellular-resolution and cell-type-specific recording and identify whether the influences of FUS on cortical astrocytes and neurons are distinctive and state dependent. MethodsHere we combined a customized 0.521MHz FUS transducer with two-photon microscopy, allowing simultaneous single-cell resoultion imaging and FUS stimulation at intensities of 0.91 or 1.5 W/cm2 to examine astrocyte and neuronal calcium responses in somatosensory cortex of both awake and lightly anesthetized mice. Functional clustering analysis was performed to identify calcium response activated or inhibited subpopulations. ResultsIn awake mice, FUS significantly enhanced the amplitude, frequency, and temporal integral of astrocyte calcium transients, while suppressing neuronal calcium activity and reducing the proportion of activated neuronal subpopulations. In contrast, lightly anesthetized mice displayed a blunted yet increased astrocyte response and negligible neuronal modulation under FUS, suggesting that baseline suppression from anesthesia partially masks FUS effects. ConclusionsOur study demonstrated that FUS elicited distinctive, state-dependent effects on cortical astrocytes and neurons, highlighting astrocytes as previously underappreciated targets of ultrasound neuromodulation. These findings will pave the way for FUS-based therapies targeting astrocyte-neuron interactions in conditions involving abnormal brain excitability. HighlightsO_LILow duty cycle low frequency focused ultrasound induced negligible heat effects. C_LIO_LIUltrasound markedly enhanced astrocyte calcium transients in awake mice. C_LIO_LIUltrasound suppressed neuronal calcium activity in awake mice. C_LIO_LIThe effects of ultrasound on both cell types were reduced under light anesthesia. C_LI

bioengineering↗

bioRxiv2024

Low intensity pulsed ultrasound activates excitatory synaptic networks in cultured hippocampal neurons

Ultrasound can non-invasively penetrate deep into brain for neuromodulation and has demonstrated good potential for clinical application. Excitation or inhibition of neurons by ultrasound has been reported, but the underlying mechanisms are largely unknown. So far most in vitro studies have focused on the activation of individual neurons by ultrasound with calcium imaging. As the focal region of ultrasound is typically millimeter or submillimeter size, it is important to investigate yet so far unclear how the mechanical effects of ultrasound would influence on the synaptic circuit activity of neurons. MethodsLow-intensity pulsed ultrasound (LIPUS) (25 MHz, 5% duty cycle, 5 Hz pulse repetition frequency, 0.4 - 1.6 W/cm2) was used to stimulate cultured hippocampal neurons. Action potentials and excitatory postsynaptic currents were recorded in individual cells with the whole-cell patch-clamp technique. We also simultaneously imaged intracellular calcium, along with neuronal electrical signals, to resolve neuronal network dynamics during LIPUS. ResultsExcitatory postsynaptic currents (EPSCs) were evoked by LIPUS in high-density neuronal cultures. Both the frequency and amplitude of EPSCs increased, indicating enhanced glutamatergic synaptic transmission. The probability of evoking responses, as well as the total charge of EPSCs evoked by ultrasound, increased with ultrasound intensity. Mechanistic analysis reveals that extracellular calcium influx, action potential (AP) firing and synaptic transmission are necessary for the responses to ultrasound in the high-density culture. In contrast, EPSCs were not enhanced in cultures with low densities of neurons. Simultaneous calcium imaging of neuronal network activity indicated that recurrent excitatory network activity is recruited during ultrasound stimulation in high-density cultures. ConclusionUltrasound can activate recurrent neuronal network activity, caused by excitatory synaptic transmission, over tens to hundreds of seconds. Our study provides insights into the mechanisms involved in the response of the brain to ultrasound and illuminates the potential to use ultrasound to regulate synaptic function in neurological disorders that involve synaptic dysfunction, such as Parkinsons disease and Alzheimers disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/614451v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@bd419org.highwire.dtl.DTLVardef@91d93corg.highwire.dtl.DTLVardef@14d0c14org.highwire.dtl.DTLVardef@153f7c4_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Dynamic simulations of feeding and respiration of the early Cambrian periderm-bearing cnidarian polyps

Although fossil evidence suggests the existence of an early muscular system in the ancient cnidarian jellyfish from the early Cambrian Kuanchuanpu biota (ca. 535 Ma), south China, the mechanisms underlying the feeding and respiration of the early jellyfish are conjectural. Recently, the polyp inside the periderm of olivooids was demonstrated to be a calyx-like structure, most likely bearing short tentacles and bundles of coronal muscles at the edge of the calyx, thus presumably contributing to feeding and respiration. Here, we simulate the contraction and expansion of the microscopic periderm-bearing olivooid Quadrapyrgites via the fluid-structure interaction computational fluid dynamics (CFD) method to investigate their feeding and respiratory activities. The simulations show that the rate of water inhalation by the polyp subumbrella is positively correlated with the rate of contraction and expansion of the coronal muscles, consistent with the previous feeding and respiration hypothesis. The dynamic simulations also show that the frequent inhalation/exhalation of water through the periderm polyp expansion/contraction conducted by the muscular system of Quadrapyrgites most likely represents the ancestral feeding and respiration patterns of Cambrian sedentary medusozoans that predated the rhythmic jet-propelled swimming of the modern jellyfish. Most importantly for these Cambrian microscopic sedentary medusozoans, the increase of body size and stronger capacity of muscle contraction may have been indispensable in the stepwise evolution of active feeding and subsequent swimming in a higher flow (or higher Reynolds number) environment. Impact statementTo the best of our knowledge, our study is the first to simulate the feeding and respiration patterns of Quadrapyrgites by introducing a dynamic fluid-structure coupling method, revealing the relationship between the ancient medusozoans and modern jellyfish.

evolutionary biology↗

bioRxiv2023

Phage administration with repeated intravenous doses leads to faster phage clearance in mammalian hosts

ObjectivesPhage therapy has shown a great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. MethodsHere, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics (PK) with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, the phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. ResultsA non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses caused that the plasma phage titer at 5 minutes dropped 2-3 Log10 compared to the first dose regardless of phage types in rats. Host innate immune responses were activated including the upregulated expression (>10-fold) of TNF- and splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. ConclusionsThe mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.

pharmacology and toxicology↗

bioRxiv2022

Hsa-miR-31-5p controls a metabolic switch in psoriatic keratinocytes that identifies therapeutic intervention

Psoriasis is characterized by a combination of keratinocyte hyperproliferation and immune cell activation. Immune cell activation requires increased glucose consumption, consequently limiting glucose availability for other cell types like keratinocytes. In psoriasis Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes. Here we show that miR-31 expression in keratinocytes is induced by limited glucose availability and increases survival under limiting glucose conditions, by increasing glutamine metabolism. In addition, miR-31 induced glutamine metabolism results in secretion of specific metabolites (aspartate and glutamate) but also immuno-modulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibition of glutaminase (GLS) using CB-839 impedes miR31-induced metabolic rewiring and secretion of immuno-modulatory factors. Concordantly, pharmacological targeting of GLS alleviated psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

immunology↗

bioRxiv2021

Investigation on the changes of Bifidobacterium and lactic acid bacteria in soybean meal fermented feed

The main objective of this research was to explore the dynamic changes of Bifidobacterium and lactic acid bacteria (LAB) in the process of feed fermentation under anaerobic condition, so as to increase the number of fermented bacteria of Bifidobacterium from the aspect of strain combination. The results showed that when Bifidobacterium lactis (B. lactis, i.e. Bifidobacterium animalis subsp. lactis) fermented with Bacillus coagulans or Lactobacillus paracasei, the maximum number of B. lactis in those samples was 9.42 times and 4.64 times of that of fermented sample with B. lactis only. The soybean meal was fermented by B. lactis, L. paracasei and B. coagulans, and the number of B. lactis reached the maximum after fermented 10 days, which was 6.13 times of that in unfermented sample. The reducing sugar content and highest activity of -galactosidase were higher than the control. These results suggest that B. coagulans and L. paracasei can promote the growth of B. lactis. It is inferred that B. coagulans can metabolize normally in aerobic, micro-aerobic and anaerobic environments, consume oxygen, produce digestive enzymes, and cooperate with L. paracasei to produce metabolic products benefit for the growth of B. lactis.

microbiology↗

bioRxiv2020

Induction of core symptoms of autism spectrum disorders by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys

Although CRISPR/Cas9 mediated gene editing is widely applied to mimic human disorders, whether acute manipulation of disease causing genes in the brain leads to behavioral abnormalities in non human primates remains to be determined. Here we induced genetic mutations in MECP2, a critical gene linked to Rett syndrome (RTT) and autism spectrum disorders (ASDs), in the hippocampus (DG and CA1~4) of adolescent rhesus monkeys (Macaca mulatta) in vivo via adeno associated virus (AAV) delivered Staphylococcus aureus Cas9 with sgRNAs targeting MECP2. In comparison to monkeys injected with AAV-SaCas9 alone (n = 4), numerous autistic-like behavioral abnormalities were identified in the AAV~SaCas9~sgMECP2 injected monkeys (n = 7), including social interaction deficits, abnormal sleep patterns, insensitivity to aversive stimuli, abnormal hand motions and defective social reward behaviors. Furthermore, some aspects of ASDs and RTT, such as stereotypic behaviors, did not appear in the MECP2 gene-edited monkeys, suggesting that different brain areas likely contribute to distinct ASD symptoms. This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates, paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.

neuroscience↗