Biology subjects

Qi, S.

Publications and source records attributed to Qi, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Targeting Tumor Immunity: Statins as a Repurposed Strategy for Preventing Ovarian Cancer Advancement

High-grade serous ovarian carcinoma (HGSOC) remains the most lethal gynecologic malignancy, characterized by a high recurrence rate and poor long-term survival. Although daily statin use is associated with improved survival in ovarian cancer patients, the underlying mechanism of this benefit remains unclear, in part due to the use of non-clinical high doses and reliance on immunodeficient murine models in preclinical studies. Here, we analyzed data from the TriNetX US Collaborative Network to evaluate the association between statin use and survival in ovarian cancer patients, confirming a survival benefit in a large U.S. cohort. We next investigated the protective effects in a syngeneic ascites tumor model of ovarian cancer. Mice treated with clinically relevant doses of lipophilic atorvastatin (ATO) exhibited prolonged survival. Single-cell transcriptomic analyses further revealed enhanced CD8+ T-cell activation programs and pro-inflammatory macrophage remodeling. Flow cytometry identified increased M1-like macrophages and activated CD8+ T-cell populations. Cytokine profiling and transcriptomic analyses indicated that IL-15 signaling was significantly elevated following ATO treatment. Multiplex immunofluorescence analyses demonstrated enhanced tertiary lymphoid structure (TLS)-associated immune organization in metastatic tumor tissues after ATO treatment, with increased T- and B-cell markers. Ex vivo culture of primary T cells with ascites supernatant from ATO-treated mice resulted in enhanced T-cell activation and migratory capacity compared with supernatant from DMSO-treated mice. Collectively, our results suggest that daily statin use may remodel the body environment into a more immune-activated state, leading to a long-term beneficial effect on survival in cancer patients, as observed in large epidemiological studies.

cancer biology↗

bioRxiv2026

OEF18 is a membrane-anchored organellar Ca{superscript 2}⁺ sensor linking calcium signaling to jasmonate-mediated defense and stress acclimation

Changes in intracellular calcium ion (Ca{superscript 2}) concentrations generate characteristic signatures that are decoded by specialized Ca{superscript 2}-binding proteins (CaBP). Although substantial progress has been made in understanding cytosolic calcium signaling pathways, calcium signaling within organelles, particularly chloroplasts, remains poorly understood, partly because only a few EF-hand CaBP have been identified in organelles. Here, we describe a novel EF-hand protein of 18 kDa, that was found to be associated with the chloroplast envelope and peroxisomal membrane and was therefore named OEF18 (ORGANELLAR EF-HAND PROTEIN OF 18 kDa). OEF18 has a very unusual structure, containing an N-terminal myristoylation site, followed by one EF-hand in the N-terminus facing to the cytosol, and a transmembrane domain in the C-terminus. OEF18 membrane-targeting was found to be mediated by ANKYRIN REPEAT-CONTAINING PROTEIN 2A (AKR2A) via the C-terminal transmembrane domain of OEF18. Furthermore, the EF-hand in OEF18 bound Ca{superscript 2} at a physiological concentration that led to a large protein conformational change, inducing oligomerization of the N-terminal part. We found that oef18 mutants accumulated less jasmonic acid (JA) and its bioactive conjugate JA-Ile, likely causing a defect in the insect herbivore response. Wild-type OEF18 complemented the herbivory phenotype of oef18 mutants, whereas an EF-hand point mutant lacking Ca{superscript 2}-binding capacity failed to restore the wild-type response. Furthermore, OEF18 was required for resistance to salt stress in combination with dark-induced senescence. Together, these results establish OEF18 as a previously unrecognized organellar Ca{superscript 2} sensor that couples Ca{superscript 2} perception to JA-mediated defense and abiotic stress responses in plants.

plant biology↗

bioRxiv2026

Phagocytic activity of perivascular cell promotes CNS injury pathology

Injury, stroke, and neurological diseases cause persistent accumulation of cellular debris that deteriorates lesion microenvironment and impedes central nervous system (CNS) repair. Debris clearance in the injured CNS has long been attributed primarily to microglia and infiltrating macrophages. Here, we identify perivascular cells as previously unrecognized phagocytes that expand after injury and exhibit robust phagocytic activity. Perivascular cell phagocytosis is conserved across multiple mouse models of CNS injury and human stroke lesions. These cells exhibit key hallmarks of phagocytosis, including LC3-associated phagocytosis for efficient lysosomal degradation. Mechanistically, phosphatidylserine serves as the eat-me signal and Axl mediates myelin debris uptake. Myelin phagocytosis drives perivascular cell proliferation, fibrosis and lesion progression. Genetic deletion of Axl in perivascular cells or pharmacological inhibition with the FDA-approved Axl inhibitor Gilteritinib reduces pathology and improves functional recovery after spinal cord injury. Together, these findings establish Axl-dependent perivascular cell phagocytosis as a therapeutic target for CNS repair.

neuroscience↗

bioRxiv2026

Architectural Confinement and Seasonal Forcing Shape Cross-Domain Pathogen Assemblages in Complex Built Environments

Airborne microbial pathogens in built environments (BEs) may pose potential health threats, yet the ecological mechanisms governing their assembly and persistence across interconnected architectural spaces are less studied. Here, we conducted a year-long, multi-spatial investigation across a university campus complex, sampling the exhaust outlets of three indoor environments and the adjacent outdoor inlets. By integrating the 16S rRNA gene and ITS sequencing from 437 paired bacterial-fungal samples, we characterized the spatiotemporal dynamics of airborne opportunistic pathogen-containing genera. Our study showed that spatial filtering emerged as the dominant determinant of pathogen community structure, with confined elevator environments serving as reservoirs of pathogens with limited but continuous microbial influx from surrounding spaces. Superimposed on this spatial baseline, bacterial and fungal pathogens displayed distinct seasonal dynamics. Opportunistic fungal pathogens such as Fusarium peaked during autumn and winter, possibly driven by enhanced aerosol persistence and dispersal under cooler, drier conditions. In contrast, bacterial pathogens exhibited greater temporal resilience, with key taxa such as Listeria transcribed actively during winter, predisposing them to increased relative abundance during spring. Cross-domain ecological networks further revealed the dynamic interactions among pathogens, centered on the skeletal structure mediated by the keystone fungal pathogen Aspergillus, suggesting that coordinated microbial interactions reinforced pathogen persistence across seasons. Together, our findings support a unified ecological framework in which pathogen dynamics within BEs arise from the coupled effects of spatial filtering, climatic modulation, and biotic interactions. These results provide a foundation for transitioning from static environmental control toward predictive pathogen management in BEs. ImportanceBEs are the primary settings of human microbial exposure, yet the ecological principles governing the persistence of airborne pathogens across interconnected indoor spaces remain poorly resolved. Most previous indoor studies have focused on isolated environments or single microbial groups, limiting our understanding of how pathogens are maintained and redistributed within complex architectural systems. By integrating bacterial and fungal community dynamics across spatial environments over four seasons, this year-long study demonstrates that the ecology of airborne pathogens is not static, but is instead dictated by a complex interplay of spatial, climatic, and biological forces. Our findings identify enclosed, high-transit elevator spaces as critical hotspots for pathogen accumulation and highlight the role of seasonal ecological reorganization in driving airborne health risks. More broadly, this work establishes a systems-level ecological framework for understanding airborne pathogen dynamics in BEs and provides a conceptual basis for developing more adaptive strategies for indoor microbial risk management.

microbiology↗

bioRxiv2026

Co-expression of IBDV VP2 and H9N2 HA by recombinant HVT induces high protection against both pathogens in chickens

Infectious bursal disease virus (IBDV) and H9N2 avian influenza virus (AIV) are significant global threats to poultry health and production. While IBDV induces severe immunosuppression, undermining host defense and vaccine efficacy, H9N2 AIV is characterized by widespread prevalence, persistent shedding, and substantial economic losses. Conventional inactivated vaccines often fail to elicit robust cellular immunity and necessitate multiple booster doses, underscoring the urgent requirement for advanced multivalent vaccination platforms. To address this, we developed a recombinant herpesvirus of turkey (rHVT BAC-VP2-HA) using a bacterial artificial chromosome (BAC) vector system, engineered to co-express the major protective antigen VP2 of IBDV and the hemagglutinin (HA) of H9N2 AIV. Genetic stability and in vitro characterization confirmed that the recombinant exhibited replication kinetics and plaque morphology comparable to parental HVT, with stable antigen expression. In SPF chickens, rHVT BAC-VP2-HA induced strong humoral immune responses against both target antigens, comparable to those elicited by a commercial inactivated vaccine. Crucially, the recombinant virus significantly enhanced cellular immunity, evidenced by markedly elevated CD3+CD8+ T cell responses. Upon challenge, the recombinant conferred high clinical protection (86%) against virulent IBDV, significantly ameliorating bursal pathology and reducing viral loads. Notably, it provided complete (100%) protection against H9N2 AIV, effectively abolishing viral shedding and suppressing viral replication in respiratory tissues. These results demonstrate that rHVT BAC-VP2-HA is a safe and efficacious candidate capable of eliciting humoral and cellular immune responses, offering a promising strategy for the integrated control of major poultry diseases. ImportanceInfectious bursal disease virus (IBDV) and H9N2 avian influenza virus (AIV) are major pathogens that frequently co-circulate in poultry, where IBDV-induced immunosuppression compromises the efficacy of vaccination against other infectious diseases. Conventional inactivated vaccines primarily induce humoral immunity and are often insufficient to prevent viral shedding or provide broad protection against multiple pathogens. In this study, we developed a recombinant herpesvirus of turkeys (HVT) vaccine co-expressing the IBDV VP2 and H9N2 HA antigens and demonstrated that it induces both robust antibody responses and enhanced CD8+ T cell immunity. Notably, this vaccine not only provided effective protection against IBDV but also completely prevented viral shedding following H9N2 challenge. These findings highlight the advantage of HVT-vectored multivalent vaccines in eliciting balanced immune responses and controlling virus transmission, providing important insights for the development of next-generation vaccines against immunosuppressive and respiratory viral co-infections in poultry.

microbiology↗

bioRxiv2025

Mining of natural diversity enables efficient and expressible peptide asparaginyl ligases

Peptide asparaginyl ligases (PALs) are powerful tools for protein engineering but are limited by natural rarity and poor expression. We mined 23 cyclotide-rich Viola species, uncovering 29 new PALs that expanded the known repertoire to 47. A dual-objective screen identified VdiPAL1 as the best-performed natural PAL, with twice efficiency of wt-VyPAL2 and 12 mg L-1 soluble expression in E. coli. A broad P2 specificity including Trp/Ile/Leu/Phe/Tyr/Met was discovered across diverse PALs, which enables sequential click-compatible liposome dual-functionalization. 1.8L[A] crystal structure of VdiPAL1 reveals a pre-organized near-attack conformation (NAC), supported by constant-pH MD simulations linking pH-dependent reactivity to NAC geometry. Our homology- and structure-based design yielded VyOpt1, a quintuple mutant of VyPAL2 with over 24-fold improved expression via enhanced cap-domain foldability in a single design-test cycle. This work expands the PAL family and demonstrates a transferable cap-domain-based engineering strategy, highlighting natural diversity as a powerful driver of enzyme discovery and optimization. TOC summaryMining of cyclotide-rich Viola genus expanded the total number of natural peptide asparaginyl ligases (PALs) to 47, including the discovery of highly expressible VdiPAL1. Its high-resolution structure provided new insights for mechanism, and its sequence guided us to a generalized PAL engineering strategy, leading to 24-fold increment in VyPAL2 expression.

biochemistry↗

bioRxiv2025

Modulating Glutamine Metabolism Reprograms Pro-Inflammatory Differentiation in Macrophages

Previous in vivo studies demonstrated that JHU083/DON, a glutamine analog drug, potently reprograms M1/M2 macrophages. To determine whether these effects are direct or indirect, we utilized an in vitro murine bone marrow-derived macrophage (BMDM) model, which recapitulates macrophage differentiation and polarization processes, to examine the impact of DON on the M1 macrophages. DON was applied during M1 differentiation or to fully polarized M1 macrophages, revealing that glutamine inhibition initially suppressed M1 activity but later enhanced it, resulting in sustained pro-inflammatory activation. Multi-omics analyses (bulk RNA-seq and LC-MS), time-course assays, and glutamine depletion experiments consistently suggested that prolonged glutamine inhibition elevates glutamine levels, which sustain pro-inflammatory gene transcription. In contrast, M2 and tumor-associated macrophages (TAM), which are immunosuppressive, were more susceptible to DON, leading to functional suppression. Collectively, our findings uncover stage-specific mechanisms by which glutamine inhibition modulates M1 polarization, offering a mechanistic rationale for therapeutic strategies that sustain pro-inflammatory, anti-tumor macrophage activity while concurrently suppressing immunosuppressive myeloid subsets in cancer.

cancer biology↗

bioRxiv2025

Unveiling the Chain Mediation Model of Sleep Quality and Fatigue in Linking Subjective Exercise Experience to Depression in Adolescent

While the positive correlation between physical exercise and depression has been widely replicated in cross-sectional research, the prognostic value of subjective exercise experience for depression continues to be disputed, and the mediating processes are not well understood. This study aims to elucidate the predictive role of subjective exercise experience in depression and examine the chain mediating effects of sleep quality and fatigue. We administered validated self-report questionnaires to assess these constructs in a sample of 538 Chinese high school students. The results demonstrated that adolescents depressive symptoms are influenced by subjective exercise experience, and this effect mediated through two independent pathways: sleep quality and fatigue. Moreover, subjective exercise experience can predict adolescent depression via either the sleep quality pathway or the fatigue pathway. The identification of mediating dual pathways provides empirical support for developing targeted exercise interventions that specifically address sleep disturbances and fatigue management in depressed adolescents.

physiology↗

bioRxiv2025

An Unexpected Role of Molecular Chaperones in Regulating the Excited States and Activities of Folded Enzymes

Molecular chaperones are recognized for assisting protein folding. Emerging evidence suggests that chaperones also interact with natively folded proteins. Yet their functional impact on folded proteins remains unclear. Here, we show that chaperones can directly modulate the conformational dynamics and catalytic efficiency of enzymes in their native states. Spy and Hsp70 increased lysozyme activity by altering conformational exchanges, and this effect extended across other chaperones and enzymes. Hsp70, Spy, Hsp104, and Hsp20 enhanced the catalytic activities of multiple folded enzymes, including alkaline phosphatase, DNA polymerase Pfu, endonucleases Cas12a/Cas13a, and xylanase. These findings uncover an unanticipated function of chaperones in regulating enzyme function expanding their mechanistic scope beyond folding assistance and suggests opportunities in enzyme engineering, diagnostics, and cellular regulation.

molecular biology↗

bioRxiv2025

Post-replicative initial expression of the cell fate regulator PAX6 during neuroectoderm differentiation

The development of multicellular organisms requires precise coordination between cell division and differentiation. Cell division generates the necessary number of cells, while differentiation creates distinct cell identities, forming tissues and organs. The transcription factors SOX2 and PAX6 specify neuroepithelial cells, the earliest neural progenitor cells (NPCs) during brain development. How lineage specification is coordinated with the cell cycle is not fully understood. Here, we show that PAX6 expression occurs during a narrow time window--between 48 and 72 hours--after neural induction of human embryonic stem cells (ESCs). Flow cytometry analyses and time-lapse imaging further show that PAX6 expression starts during the G2 phase of the cell cycle. We identify a novel 500-bp PAX6 promoter that drives its G2-specific expression. PAX6 expression is independent of known regulators of cell-cycle-dependent transcription, suggesting the existence of a novel mechanism. S-phase block by hydroxyurea prevents PAX6 expression and differentiation into NPC. Thus, NPC fate specification is coupled to cell cycle progression and occurs after the completion of DNA replication. This post-replicative lineage commitment ensures the creation of two daughter cells of identical cell fate following cell division.

cell biology↗

bioRxiv2025

Cryo-EM structure of DNA-unbound human MCM2-7 complex reveals new disease-relevant regulation

Chromatin loading of the hexameric replicative helicase MCM2-7 complex requires coordinated interactions with the origin recognition complex (ORC), CDC6, and CDT1. MCM2-7 not bound to DNA forms a single hexamer (SH) with an open DNA entry gate. Two MCM2-7 SHs are loaded sequentially to form the double hexamer (DH) that encircles the DNA duplex. Activated MCM2-7 then unwinds DNA and initiates DNA replication. Our cryo-electron microscopy analyses show that a fraction of human MCM2-7 without DNA exists as DH. Unexpectedly, we find that the MCM3 winged helix domain (WHD) docks on MCM2 in both DNA-free DH and SH, creating a safety latch across the DNA entry gate to block DNA entry into the central channel. The safety latch can be opened by ORC-CDC6 binding. Disrupting this latch by designed or human disease-related mutations of MCM3 causes replication defects and DNA damage checkpoint activation. Our findings uncover a new regulated step in MCM2-7 loading with implications for human diseases.

biophysics↗

bioRxiv2025

CCN1 forms a complex with GPC4 and heparin to fine-tune signaling activities for embryonic cortical neural stem cell maintenance

Radial glial cells (RGCs) are the neural stem cells (NSCs) in the developing brain, capable of self-renewing and generating neurons and glia in order. The developmental behaviors of NSCs are determined by extrinsic factors from the NSC niche, together with intrinsic factors. Here, we show that Cellular Communication Network 1 (CCN1), a secreted matricellular protein, is an autocrine factor derived from RGCs in the embryonic telencephalon. Loss of Ccn1 in RGCs leads to accelerated lineage progression of RGCs, and causes premature cell cycle exit and neuronal differentiation, resulting in a reduction in NSC pool size, and in turn, at the expense of the perinatal gliogenesis. Mechanistically, CCN1 interacts with an RGC-expressed membrane protein GPC4, one of the heparan sulfate proteoglycans (HSPGs), and is required for GPC4 to maintain NSCs through the Sonic Hedgehog (Shh) signaling pathway, depending on the binding of heparin to CCN1. Our work provides a potential mechanism for the dynamic and sophisticated interconnections of niche components that meet the needs of context-dependent maintenance, differentiation, and fate determination of NSCs.

developmental biology↗

bioRxiv2025

Perturbing RNA localization for functional study in neurons

Spatial RNA organization plays a pivotal role in diverse cellular processes and diseases, but the functional implications of spatial RNA localization remain underexplored. We present CRISPR-mediated transcriptome organization (CRISPR-TO) that harnesses RNA-guided, nuclease-dead dCas13 for programmable control of RNA localization in live cells. CRISPR-TO enables targeted localization of RNAs to diverse subcellular compartments, including p-bodies, stress granules, telomeres, and nuclear stress bodies, across cell types. In primary cortical neurons, we demonstrate that repositioned mRNAs undergo local translation along neurites and at neurite tips and co-transport with ribosomes, with {beta}-actin mRNA localization enhancing the formation of dynamic filopodial protrusions and inhibiting axonal regeneration. Furthermore, CRISPR-TO-enabled parallel screening in primary neurons identifies Stmn2 mRNA localization as a driver of neurite outgrowth. By enabling large-scale perturbation of the spatial transcriptome, CRISPR-TO bridges a critical gap left by current sequencing and imaging technologies, offering a versatile platform for high-throughput functional interrogation of RNA localization in living cells and organisms.

bioengineering↗

bioRxiv2024

Structural Insights into the Assembly and Regulation of 2'-O RNA Methylation by SARS-CoV-2 nsp16/nsp10

2-O-ribose methylation of the first transcribed base (adenine or A1 in SARS-CoV-2) of viral RNA mimics the host RNAs and subverts the innate immune response. How nsp16, with its obligate partner nsp10, assembles on the 5-end of SARS-CoV-2 mRNA to methylate the A1 has not been fully understood. We present a [~] 2.4 [A] crystal structure of the heterotetrameric complex formed by the cooperative assembly of two nsp16/nsp10 heterodimers with one 10-mer Cap-1 RNA (product) bound to each. An aromatic zipper-like motif in nsp16 and the N-terminal regions of nsp10 and nsp16 orchestrate an oligomeric assembly for efficient methylation. The front catalytic pocket of nsp16 stabilizes the upstream portion of the RNA while the downstream RNA remains unresolved, likely due to its flexibility. An inverted nsp16 dimer extends the positively charged surface area for longer RNA to influence the catalysis. Additionally, a non-specific nucleotide-binding pocket on the backside of nsp16 plays a critical role in catalysis, further contributing to its enzymatic activity.

microbiology↗

bioRxiv2024

Structural architecture of amyloid-β oligomers, curvilinear protofibrils and annular assemblies, imaged by cryo-EM and cryo-ET

Small prefibrillar structures of the amyloid-{beta} peptide (A{beta}) are believed to be central to cytotoxicity in Alzheimers disease, the most common form of dementia. A snapshot of these prefibrillar assemblies has therefore been characterized using a combination of cryo-ET and cryo-EM single particle analysis. This has facilitated an understanding of the relationship between, oligomers, curvilinear protofibrils and annular assemblies. A highly consistent diameter for all curvilinear protofibrils and oligomers of 28 [A], indicates that these assemblies are simply structural extensions from the smaller oligomers. Furthermore, their basic crosssection suggests mature amyloid fibrils might be initiated by the lateral binding of two curvilinear protofibrils. Ab-initio 3D reconstruction also reveals ring-shaped annular assemblies. These possess a central internal channel, ca. 14 [A] in diameter and 54 [A] long, which is capable of traversing lipid membranes. Large conductance recorded using patch-clamp electrophysiology, match the internal diameter of the A{beta} annular architecture.

biophysics↗

bioRxiv2024

Dorsal Raphe to Basolateral Amygdala Corticotropin-Releasing Factor Circuit Regulates Cocaine-Memory Reconsolidation

Environmental stimuli elicit drug craving and relapse in cocaine users by triggering the retrieval of strong cocaine-related contextual memories. Retrieval can also destabilize drug memories, requiring reconsolidation, a protein synthesis-dependent storage process, to maintain memory strength. Corticotropin-releasing factor (CRF) signaling in the basolateral amygdala (BLA) is necessary for cocaine-memory reconsolidation. We have hypothesized that a critical source of CRF in the BLA is the dorsal raphe nucleus (DR) based on its neurochemistry, anatomical connectivity, and requisite involvement in cocaine-memory reconsolidation. To test this hypothesis, male and female Sprague-Dawley rats received adeno-associated viruses to express Gi-coupled designer receptors exclusively activated by designer drugs (DREADDs) selectively in CRF neurons of the DR and injection cannulae directed at the BLA. The rats were trained to self-administer cocaine in a distinct environmental context then received extinction training in a different context. They were then briefly re-exposed to the cocaine-predictive context to destabilize (reactivate) cocaine memories. Intra-BLA infusions of the DREADD agonist deschloroclozapine (DCZ; 0.1 mM, 0.5 L/hemisphere) after memory reactivation attenuated cocaine-memory strength, relative to vehicle infusion. This was indicated by a selective, DCZ-induced and memory reactivation-dependent decrease in drug-seeking behavior in the cocaine-predictive context in DREADD-expressing males and females at test compared to respective controls. Notably, BLA-projecting DR CRF neurons that exhibited increased c-Fos expression during memory reconsolidation co-expressed glutamatergic and serotonergic neuronal markers. Together, these findings suggest that the DRCRF [->] BLA circuit is engaged to maintain cocaine-memory strength after memory destabilization, and this phenomenon may be mediated by DR CRF, glutamate, and/or serotonin release in the BLA.

neuroscience↗

bioRxiv2024

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

Magnesium (Mg) deficiency is associated with increased risk and malignancy of colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomics and phosphoproteomics indicated that low tumorous Mg content may activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p upregulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1-ACTN4 interaction by decreasing DBN1S142p, which, in turn, enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may offer a promising preventive and therapeutic strategy for CRC.

cancer biology↗

bioRxiv2024

An intracranial dissection of human escape circuits

Predators attack at different spatiotemporal scales, spurring prey to elicit escape responses that range from simple motor reactions and strategic planning that involve more complex cognitive processes. Recent work in humans suggests that escape relies on two distinct circuits: the reactive and cognitive fear circuits. However, the specific involvement of these two circuits in different stages of human escaping remains poorly characterized. In this study, we recorded intracranial electroencephalography (iEEG) from epilepsy patients while they performed a modified flight initiation distance (FID) task. We found brain regions in the cognitive fear circuit, including the ventromedial prefrontal cortex and hippocampus, encoded the threat level during the information processing stage. The actual escaping stage, especially under rapid attack, prominently activated areas within the reactive fear circuit, including the midcingulate cortex and amygdala. Furthermore, we observed a negative correlation between the high gamma activity (HGA) of the amygdala and the HGA of the vmPFC and HPC under rapid attacks. This indicates that the amygdala may suppress the activity of the cognitive fear circuit under rapid attacks, enabling the organism to react quickly to ensure survival under the imminent threat. These findings highlight the distinct roles of the reactive and cognitive fear circuits in human escaping and provide accounts for the importance of fear in human survival decisions.

neuroscience↗