Biology subjects

She, X.

Publications and source records attributed to She, X..

8 recordsLinked to original sources

bioRxiv2026

Language Dysfunction Associated with Pathological Brain Connectivity in Children with Epilepsy

Language impairment is common in childhood epilepsy and may arise in part from disruption of the distributed brain networks that support language. In self-limited epilepsy with centrotemporal spikes (SeLECTS)--the most common focal epilepsy of childhood--hyperconnectivity has been linked to poor language outcomes, but the specific network patterns associated with language dysfunction remain unclear, limiting the ability to target neurostimulation rationally. We recorded high-density EEG from 27 children with SeLECTS and 29 age-matched controls during verb generation and rest, and quantified functional connectivity across multiple frequency bands and bilateral frontal, temporal, occipital, and motor regions. Using multivariate pattern analysis, we identified connectivity patterns that predicted language ability, distinguished patterns shared across groups from those specific to SeLECTS and tested whether spatially specific connectivity provided information beyond whole-brain or hemispheric averages and conventional clinical variables. Frontal and occipitotemporal connectivity, particularly within the left hemisphere, predicted language ability across groups, whereas motor-network connectivity emerged as the dominant SeLECTS-specific predictor, linking the epileptogenic network to language dysfunction. Connectivity between specific regions outperformed averaged connectivity measures and predicted language beyond epilepsy diagnosis and antiseizure medication use. Task-based connectivity also outperformed resting-state connectivity. These findings show that language ability is associated with distributed yet spatially specific patterns of brain connectivity, while epilepsy introduces distinct alterations centered on the epileptogenic network. Identifying these disease-specific network patterns provides mechanistic insight into language dysfunction and a rational basis for spatially targeted neuromodulation.

neuroscience↗

bioRxiv2026

TMS timed to interictal epileptiform discharges

Interictal epileptiform discharges (IEDs) are pathological hypersynchronous bursts of electrical brain activity that occur between seizures in patients with epilepsy. IEDs are caused by transient brain states that are difficult to predict, making them a challenging neurophysiological and technological case for brain-state-dependent stimulation. Administering stimulation at IED onset may provide insight into the epileptic network and optimize neurostimulation therapies. Here, we assessed the feasibility of IED-triggered transcranial magnetic stimulation (TMS) in two children with self-limited epilepsy with centrotemporal spikes (SeLECTS), a common pediatric epilepsy in which IEDs emerge from the motor cortex. A convolutional neural network (CNN) was trained on the participants pre-recorded electroencephalography (EEG) data with IEDs annotated by an epileptologist. The CNN was integrated into an EEG-processing pipeline that classified EEG segments as "IED" or "non-IED" in real time. With this pipeline, TMS pulses were administered during IED or non-IED periods in an interleaved, randomized design. We stimulated both the motor cortex generating the IEDs and the contralateral motor cortex and tested the impact of IEDs on TMS-evoked potentials (TEPs). Our study demonstrated that TMS can be timed to IEDs and that there is a site-specific increase in TEP amplitude when stimulating during IEDs. Out of the TMS pulses aimed at an IED, 39% and 19% were successfully delivered during an IED for the two participants, respectively. For future research, we propose ways to address the methodological challenges of IED-timed TMS, enabling brain-state-dependent TMS for epilepsy research and treatment.

neuroscience↗

bioRxiv2025

Optimization of fermentation conditions for Metarhizium robertsii and its effect on rice growth

Metarhizium robertsii is an important entomopathogenic fungus and plant endophyte, possessing dual functionality as both an insecticide and a plant growth promoter, which has led to its widespread application in agriculture. However, the effects and underlying mechanisms of M. robertsii (MAA)in promoting rice growth remain poorly understood. This study confirmed the growth-promoting effects of MAA and its fermentation supernatant on rice. Based on single-factor and response surface methodology experiments, the fermentation conditions of MAA were subsequently optimized using rice root length as a key indicator, and the potential mechanisms behind this growth promotion were preliminarily investigated. The results demonstrated that both MAA and its fermentation supernatant exerted significant growth-promoting effects on rice. Sucrose and peptone were identified as the optimal carbon and nitrogen sources, respectively. The most pronounced effect was observed when the fermentation supernatant, produced under the conditions of pH 6.0, 0.2% {beta}-Ala, and 100 mol/L Al2(SO4)3, was applied, resulting in a 21.7% increase in rice root length compared to the control group. Furthermore, significant enhancements in chlorophyll content and denser root hairs were recorded in rice treated with the MAA fermentation supernatant, with the chlorophyll content increasing by 28.17% compared to the control. These findings provide a theoretical basis for the development and application of green and efficient bio-inoculants. IMPORTANCEMetarhizium robertsii is an endogenous plant fungus that can be effective for efficient insect control, but the plant-promoting effect of this fungus and its related studies are less reported. The colonization ability and growth promotion effect of Metarhizium robertsii on different crops vary. In this study, a sterile hydroponic system for rice was established. The research found that Metarhizium robertsii can colonize the root system of rice, significantly promoting rice growth, and its growtion-promoting effect is affected by the differences in its fermentation products. After the optimization of the response surface of the fermentation conditions of Metarhizium robertsii, its growth-promoting ability increased by 21.7%. Developing microbial biofertilizers/biopesticides as a basis for reducing chemical inputs in rice cultivation.

microbiology↗

bioRxiv2025

Abnormal Elevated Connectivity During Language Processing is Associated with Poor Cognitive Performance in Children with Self-limited Epilepsy with Centrotemporal Spikes

Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) is associated with language impairments despite seizures originating in the motor cortex, suggesting aberrant cross-network interactions. Here we tested whether functional connectivity in SeLECTS during language tasks predicts language performance. We recorded high-density EEG from right-handed children with SeLECTS (n=31) and age-matched controls (n=32) during verb generation, repetition, and resting tasks. Phonological awareness was assessed using the Comprehensive Test of Phonological Processing-2. Connectivity between bilateral motor cortices and language regions (the left inferior frontal and superior temporal cortices and their right hemisphere homologues) was measured using weighted Phase Lag Index (wPLI). Children with SeLECTS demonstrated significantly elevated connectivity between motor and language regions during language processing. Motor-to-frontal connectivity was higher in SeLECTS during both verb generation and repetition tasks. Frontal-to-temporal connectivity was elevated specifically during verb generation. Higher interhemispheric connectivity (between the left and right hemispheres) during language tasks strongly predicted worse phonological awareness in children with SeLECTS ({beta}= -40 to -61, all p<0.005), but not controls. Together, we found that children with SeLECTS exhibited pathologically elevated connectivity between motor and language networks that was strongly associated with impaired phonological awareness. These findings identify aberrant interhemispheric connectivity as a pathophysiological mechanism underlying language dysfunction and establish EEG-based connectivity measures as a potential biomarker for guiding targeted neuromodulation therapies to treat cognitive impairments in pediatric epilepsy.

neuroscience↗

bioRxiv2024

The E3 ligase NEDD4L prevents colorectal cancer liver metastasis via degradation of PRMT5 to inhibit the AKT/mTOR signaling pathway

Colorectal cancer is the second most common cause of cancer mortality worldwide, and liver metastasis is the major cause of death in patients with colorectal cancer. Dysfunctional E3 ligase activity has recently been shown to be associated with colorectal cancer. However, the key E3 ligase affecting colorectal cancer liver metastasis remains unknown. Therefore, we used an shRNA library targeting 156 E3 ubiquitin ligases to perform an in vivo loss-of-function screen of a human colorectal cancer cell line in a mouse model of colorectal cancer liver metastasis. The screen revealed that NEDD4L knockdown promoted colorectal cancer liver metastasis. Moreover, overexpression of NEDD4L prevented colorectal cancer liver metastasis. Mechanistic studies revealed that NEDD4L bound to the PPNAY motif in PRMT5 and ubiquitinated PRMT5 to promote its degradation. PRMT5 degradation attenuated the methylation of an arginine residue in AKT1 to inhibit the AKT/mTOR signaling pathway, consequently decreasing colorectal cancer cell proliferation. We are the first to show that PRMT5 is a substrate protein of the E3 ligase NEDD4L and reveals not only the metastasis-inhibiting function of NEDD4L but also a novel mechanism by which NEDD4L suppresses colorectal cancer liver metastasis. These findings may provide a new preventive strategy for liver metastasis.

cancer biology↗

bioRxiv2024

Weekly inhaled salmeterol xinafoate, a selective β2 adrenergic receptor agonist drug, therapeutically inhibits cancer growth and prolongs survival in vivo

Humans have spent approximately 99.5% of the 2.5 million years of evolutionary history as hunter-gatherers, which helped to evolutionarily mold our minds and bodies to the hunting and gathering lifestyle. Physical activity associated with hunting animals, gathering plants, and evading predators is essential for human survival, evolution, and prosperity. Thus, physical activity (acute stress) is mostly beneficial to the body, whereas psycho-emotional stress (chronic stress) is usually detrimental at the psychological, physiological, and pathological levels. Although physical activity exerts anticancer effects and psycho-emotional stress exhibits cancer-promoting effects, both function through the same pathway involving activation of the sympathetic nervous system, release of catecholamines, and stimulation of {beta}2 adrenergic receptor ({beta}2AR) expressed on cancer cells. Here, salmeterol xinafoate was chosen to mimic physical activity. A once-weekly administration of salmeterol xinafoate by the intraperitoneal, inhalation, or transdermal route, dose-dependently extended latency, reduced cancer incidence and growth, and prolonged survival in vivo. Remarkably, the best complete response rates were 75%, 30%, and 71.43% for the therapeutic treatment of lung cancer, breast cancer, and melanoma, respectively. Notably, the salmeterol xinafoate doses used in our experiments are comparable to those used in patients. Moreover, in endogenous {beta}2AR knockout cancer cells, the exogenous {beta}2AR mutant with impaired salmeterol xinafoate binding or downstream signaling prevented the anticancer effects of salmeterol xinafoate in vivo, demonstrating the on-target action of salmeterol xinafoate on cancer cells and the requirement of the downstream signaling pathway. Finally, we showed that treatment with salmeterol xinafoate dose-dependently decreased the self-renewal capacity of lung cancer stem cells, breast cancer stem cells, and melanoma stem cells. From the perspective of human evolution into cancer biology, our study reveals that {beta}2AR represents an ideal anticancer drug target and that salmeterol xinafoate monotherapy has strong anticancer activity.

cancer biology↗

bioRxiv2024

Strong segregation promotes self-destructive cooperation

Self-destructive cooperator (SDC), where individuals sacrifice themselves for others, poses significant personal costs yet is widespread in nature. Traditional group selection theory struggles to explain its persistence, as the extreme cost of self-destruction typically exceeds the benefit to these individuals. Here, we predict that this behavior can endure in structured environments with strong segregation, where populations are divided into homogenous groups originating from one or two founding members. In such contexts, the benefits derived from SDC are primarily confined within the homogenous SDC groups, thus preserving the value of this altruistic sacrifice and ensuring its maintenance. To validate our hypothesis, we employ a synthetic system with engineered bacteria to mimic both SDC and non-sacrificing cheaters. We then conduct automated experiments facilitated by biofoundry technology to monitor and operate the subgroups with diverse growth behaviors stemming from a restricted number of initial cells because of strong segregation. Eventually, we demonstrate that SDC indeed maintains under strong segregation, and high stress benefits SDC because it reduces the benefits received by cheaters in heterogenous subgroups. This study extends the group selection theory to encompass even the most extreme manifestations of altruism and highlights the potential of automation in evolutionary research.

microbiology↗

bioRxiv2017

Inhibition of mitochondrial fission preserves photoreceptors after retinal detachment

Photoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgeries have been well developed to restore retinal structures, post-op patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored. In this study, we show that after experimental RD induction, photoreceptors activate dynamin-related protein 1 (Drp1)-dependent mitochondrial fission pathway and subsequent apoptotic cascades. Mechanistically, endogenous ROS is necessary for Drp1 activation in vivo and exogenous ROS insult is sufficient to activate Drp1-dependent mitochondrial fission in cultured photoreceptors. Accordingly, inhibition of Drp1 activity effectively preserves mitochondrial integrity and rescues photoreceptors. Collectively, our data delineates a ROS-Drp1-mitochondria axis that promotes photoreceptor degeneration in retinal diseased models.

neuroscience↗