Biology subjects

Wang, C.

Publications and source records attributed to Wang, C..

At least 523 records · Page 29Linked to original sources

bioRxiv2023

Potential clinical value and influence of conductivity in conductive cardiac patches for reducing post-MI arrythmia risks

Conductive cardiac patches can help to restore electric signal conduction of the diseased myocardium after myocardial infarction (MI). However, none of the conductive cardiac patches reported in literature has entered clinical trials. Bench-to-bedside translation of conductive patches has long been hindered by the lack of knowledge of the optimal patch conductivity and deep understanding of the potential clinical benefits and risks in patients. Here, we first prepared conductive cardiac patches with conductivities covering 5 orders of magnitude (10-3-101 S/cm). Disagreeing with the mainstream opinion that patch conductivity close to native myocardium (10-3-10-2 S/cm) is most favorable, our results showed that patches with conductivity two orders of magnitudes higher than native myocardium (10-1-100 S/cm) are most effective in restoring cardiac conduction and lowering inducibility quotient. Conduction velocity (CV) is the essence of the observed results. Rat experiments showed that the low-conductivity patch could increase the CV of infarcted myocardium, but did not fully compensate the mismatch in the CVs of infarct and healthy myocardium. Moderate-conductivity patches could increase myocardial CV to the same level of healthy myocardium, while high-conductivity patches further increased myocardial CV, causing a reversed mismatch. The relationship between patch conductivity and improved CVs in myocardium can be explained by monodomain model theory. Based on the theory, 3D finite element simulation of a MI patient heart predicted that a suitable, patch-improved myocardial CV could reduce the number of reentrants, and stabilize the remaining reentry circuits in the myocardium of the MI patient, which indicated its clinical value.

bioengineering↗

bioRxiv2023

MERITS: a web-based integrated MycobacterialPE/PPE protein database

MotivationPE/PPE proteins, highly abundant in the Mycobacterium genome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms of Mycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins. ResultsAddressing this gap, we introduce MERITS, a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22,353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localisation, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing Features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins. Availability and implementationMERITS is freely accessible at http://merits.unimelb-biotools.cloud.edu.au/.

bioinformatics↗

bioRxiv2023

A neurotransmitter atlas of the nervous system of C.elegans males and hermaphrodites

Mapping neurotransmitter identities to neurons is key to understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In the C. elegans nervous system, neurotransmitter identities have been largely assigned by expression pattern analysis of neurotransmitter pathway genes that encode neurotransmitter biosynthetic enzymes or transporters. However, many of these assignments have relied on multicopy reporter transgenes that may lack relevant cis-regulatory information and therefore may not provide an accurate picture of neurotransmitter usage. We analyzed the expression patterns of 16 CRISPR/Cas9-engineered knock-in reporter strains for all main types of neurotransmitters in C. elegans (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, and octopamine) in both the hermaphrodite and the male. Our analysis reveals novel sites of expression of these neurotransmitter systems within both neurons and glia, as well as non-neural cells. The resulting expression atlas defines neurons that may be exclusively neuropeptidergic, substantially expands the repertoire of neurons capable of co-transmitting multiple neurotransmitters, and identifies novel neurons that uptake monoaminergic neurotransmitters. Furthermore, we also observed unusual co-expression patterns of monoaminergic synthesis pathway genes, suggesting the existence of novel monoaminergic transmitters. Our analysis results in what constitutes the most extensive whole-animal-wide map of neurotransmitter usage to date, paving the way for a better understanding of neuronal communication and neuronal identity specification in C. elegans.

neuroscience↗

bioRxiv2023

Single-cell and spatial multiomic inference of gene regulatory networks using SCRIPro

The accurate reconstruction of gene regulation networks (GRNs) from sparse and noisy single-cell or spatial multi-omics data remains a challenge. Here, we present SCRIPro, a comprehensive computational framework that robustly infers GRNs for both single-cell and spatial multi-omics data. SCRIPro first addresses sample sparseness by a density clustering approach. SCRIPro assesses transcriptional regulator (TR) importance through chromatin reconstruction and in silico deletion, referencing 1,292 human and 994 mouse TRs. It combines TR-target importance scores with expression levels for precise GRN reconstruction. Finally, we benchmarked SCRIPro on diverse datasets, it outperforms existing motif-based methods and accurately reconstructs cell type-specific, stage-specific, and region-specific GRNs.

bioinformatics↗

bioRxiv2023

Identification of a Novel Ferroptosis Inducer with Dual Modulatory Effects on GPX4 Activity and Stability

Ferroptosis is a unique form of intracellular iron-dependent cell death that differs from apoptosis, necrosis, and autophagy. GPX4, an antioxidant defense enzyme, plays a pivotal role as regulator of ferroptosis. Extensive researches suggest that targeting GPX4 holds promise for cancer therapy. However, the current GPX4 inhibitors face challenges due to unfavorable drug-like properties, which hinder their progress in clinical development. In this study, we identified a novel inhibitor called MI-2, demonstrating potent ferroptosis-inducing capacity. Mechanistically, MI-2 effectively inhibits the activity of GPX4 by direct interaction. Furthermore, MI-2 promotes the degradation of GPX4 through its well-established target, MALT1. In multiple cancer models, MI-2 has demonstrated synergistic effects when combined with sorafenib or regorafenib, resulting in enhanced ferroptosis induction. These findings highlight the dual modulatory effects of MI-2 on GPX4 activity and stability, offering a promising starting point for the development of drug-like GPX4 inhibitors with translational potential.

cell biology↗

bioRxiv2023

Unexpected roles for AMPK in suppression of autophagy and reactivation of mTORC1 signaling during prolonged amino acid deprivation

AMPK promotes catabolic and suppresses anabolic cell metabolism to promote cell survival during energetic stress, in part by inhibiting mTORC1, an anabolic kinase requiring sufficient levels of amino acids. We found that cells lacking AMPK displayed increased apoptotic cell death during nutrient stress caused by prolonged amino acid deprivation. We presumed that impaired autophagy explained this phenotype, as a prevailing view posits that AMPK initiates autophagy (often a pro-survival response) through phosphorylation of ULK1. Unexpectedly, however, autophagy remained unimpaired in cells lacking AMPK, as monitored by several autophagic readouts in several cell lines. More surprisingly, the absence of AMPK increased ULK1 signaling and LC3b lipidation during amino acid deprivation while AMPK-mediated phosphorylation of ULK1 S555 (a site proposed to initiate autophagy) decreased upon amino acid withdrawal or pharmacological mTORC1 inhibition. In addition, activation of AMPK with compound 991, glucose deprivation, or AICAR blunted autophagy induced by amino acid withdrawal. These results demonstrate that AMPK activation and glucose deprivation suppress autophagy. As AMPK controlled autophagy in an unexpected direction, we examined how AMPK controls mTORC1 signaling. Paradoxically, we observed impaired reactivation of mTORC1 in cells lacking AMPK upon prolonged amino acid deprivation. Together these results oppose established views that AMPK promotes autophagy and inhibits mTORC1 universally. Moreover, they reveal unexpected roles for AMPK in the suppression of autophagy and the support of mTORC1 signaling in the context of prolonged amino acid deprivation. These findings prompt a reevaluation of how AMPK and its control of autophagy and mTORC1 impact health and disease.

cell biology↗

bioRxiv2023

(CA)n oligonucleotides correct RNA mis-splicing in TDP-43 pathology

Withdrawal StatementThe authors have withdrawn their manuscript owing to not all authors having approved the manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

molecular biology↗

bioRxiv2023

Seasonal tissue-specific gene expression reveals reproductive and stress-related transcriptional systems in wild crown-of-thorns starfish

Animals are influenced by the season, yet we know little about the changes that occur in most species throughout the year. This is particularly true in tropical marine animals that experience relatively small annual temperature and daylight changes. Like many coral reef inhabitants, the crown-of-thorns starfish (COTS), well known as a notorious consumer of corals and destroyer of coral reefs, reproduces exclusively in the summer. By comparing gene expression in seven somatic tissues procured from wild COTS sampled on the Great Barrier Reef, we identified more than 2,000 protein-coding genes that change significantly between summer and winter. COTS genes that appear to mediate conspecific communication - including both signalling factors released into the surrounding sea water and cell surface receptors - are upregulated in external secretory and sensory tissues in the summer, often in a sex-specific manner. The sexually dimorphic gene expression appears to be underpinned by sex- and season-specific transcription factors (TFs) and gene regulatory programs. There are over 100 TFs that are seasonally expressed, 86% of which are significantly upregulated in the summer. Six nuclear receptors are upregulated in all tissues in the summer, suggesting that systemic seasonal changes are hormonally controlled, as occurs in vertebrates. Unexpectedly, there is a suite of stress-related chaperone proteins and TFs, including HIF, ATF3, C/EBP, CREB and NF-{kappa}B, that are uniquely co-expressed in gravid females. The upregulation of these stress proteins in the summer suggests the demands of oogenesis in this highly fecund starfish affects protein stability and turnover in somatic cells. Together, these circannual changes in COTS gene expression provide novel insights into seasonal changes in this coral reef pest and have the potential to identify vulnerabilities for targeted biocontrol.

zoology↗

bioRxiv2023

The activated plant NRC4 immune receptor forms a hexameric resistosome

Innate immune responses against microbial pathogens in both plants and animals are regulated by intracellular receptors known as Nucleotide-binding Leucine-rich Repeats (NLR) proteins. In plants, these NLRs play a crucial role in recognizing pathogen effectors, thereby initiating the activation of immune defense mechanisms. Notably, certain NLRs serve as "helper" NLR immune receptors (hNLR), working in tandem with "sensor" NLR immune receptors (sNLR) counterparts to orchestrate downstream signaling events to express disease resistance. In this study, we reconstituted and determined the cryo-EM structure of the hNLR required for cell death 4 (NRC4) resistosome. The auto-active NRC4 formed a previously unanticipated hexameric configuration, triggering immune responses associated with Ca2+ influx into the cytosol. Furthermore, we uncovered a dodecameric state of NRC4, where the coil-coil (CC) domain is embedded within the complex, suggesting an inactive state, and expanding our understanding of the regulation of plant immune responses. One Sentence SummaryThe hexameric NRC4 resistosome mediates cell death associated with cytosolic Ca2+ influx.

plant biology↗

bioRxiv2023

Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts

In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the efficiency of this induction process. This study aimed to improve the differentiation efficiency of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunofluorescence staining, transmission electron microscopy, and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and HCN4) in both groups, with higher protein expression in the stretch group. Additionally, sarcomere length in the stretch group was notably larger than in the control group. A significant increase in the contractility of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturity and differentiation efficiency of iPS-CMs co-cultured with fibroblasts.

cell biology↗

bioRxiv2023

Allocator is a graph neural network-based framework for mRNA subcellular localization prediction

MotivationThe asymmetrical distribution of expressed mRNAs tightly controls the precise synthesis of proteins within human cells. This non-uniform distribution, a cornerstone of developmental biology, plays a pivotal role in numerous cellular processes. To advance our comprehension of gene regulatory networks, it is essential to develop computational tools for accurately identifying the subcellular localizations of mRNAs. However, considering multi-localization phenomena remains limited in existing approaches, with none considering the influence of RNAs secondary structure. ResultsIn this study, we propose Allocator, a multi-view parallel deep learning framework that seamlessly integrates the RNA sequence-level and structure-level information, enhancing the prediction of mRNA multi-localization. The Allocator models equip four efficient feature extractors, each designed to handle different inputs. Two are tailored for sequence-based inputs, incorporating multilayer perceptron and multi-head self-attention mechanisms. The other two are specialized in processing structure-based inputs, employing graph neural networks. Benchmarking results underscore Allocators superiority over state-of-the-art methods, showcasing its strength in revealing intricate localization associations. AvailabilityThe webserver of Allocator is available at http://Allocator.unimelb-biotools.cloud.edu.au; the source code and datasets are available at https://github.com/lifuyi774/Allocator

bioinformatics↗

bioRxiv2023

Pan-azole- and multi-fungicide-resistant Aspergillus fumigatus is widespread in the United States

Aspergillus fumigatus is an important global fungal pathogen of humans. Azole drugs are among the most effective treatments for A. fumigatus infection. Azoles are also widely used in agriculture as fungicides against fungal pathogens of crops. Azole-resistant A. fumigatus has been increasing in Europe and Asia for two decades where clinical resistance is thought to be driven by agricultural use of azole fungicides. The most prevalent mechanisms of azole resistance in A. fumigatus are tandem repeats (TR) in the cyp51A promoter coupled with mutations in the coding region which result in resistance to multiple azole drugs (pan-azole resistance). Azole-resistant A. fumigatus has been isolated from patients in the United States (U.S.), but little is known about its environmental distribution. To better understand the distribution of azole-resistant A. fumigatus in the U.S., we collected isolates from agricultural sites in 8 states and tested 202 isolates for sensitivity to azoles. We found azole-resistant A. fumigatus in agricultural environments in 7 states showing that it is widespread in the U.S. We sequenced environmental isolates representing the range of U.S. sample sites and compared them with publicly available environmental worldwide isolates in phylogenetic, principal component, and ADMIXTURE analyses. We found worldwide isolates fell into three clades and that TR-based pan-azole resistance was largely in a single clade that was strongly associated with resistance to multiple agricultural fungicides. We also found high levels of gene flow with clear recombination between two clades highlighting the potential for azole-resistance to continue spreading in the U.S. ImportanceAspergillus fumigatus is a fungal pathogen of humans that causes over 250,000 invasive infections each year. It is found in soils, plant debris and compost. Azoles are the first line of defense antifungal drugs against A. fumigatus. Azoles are also used as agricultural fungicides to combat other fungi that attack plants. Azole-resistant A. fumigatus has been a problem in Europe and Asia for twenty years and has recently been reported in patients in the U.S. Until this study we didnt know much about azole-resistant A. fumigatus in agricultural settings in the U.S. In this study we isolated azole-resistant A. fumigatus from multiple states and compared it to isolates from around the world. We show that A. fumigatus that is resistant to azoles and to other strictly agricultural fungicides is widespread in the U.S.

microbiology↗

bioRxiv2023

Benchmarking the translational potential of spatial gene expression prediction from histology

Spatial transcriptomics has enabled the quantification of gene expression at spatial coordinates, offering crucial insights into molecular underpinnings of diseases. In light of this, several methods predicting spatial gene expression from paired histology images have offered the opportunity of enhancing the utility of readily obtainable and cost-effective haematoxylin-and-eosin-stained histology images. To this end, we conducted a comprehensive benchmarking study encompassing six developed methods. These methods were reproduced and evaluated using HER2-positive breast tumour and human cutaneous squamous cell carcinoma datasets, followed by external validation using The Cancer Genome Atlas data. Our evaluation incorporates diverse metrics which capture the performance of predicted gene expression, model generalisability, translational potential, usability and computational efficiency of each method. Our findings demonstrate the capacity of methods to spatial gene expression from histology and highlight key areas that can be addressed to support the advancement of this emerging field.

bioinformatics↗

bioRxiv2023

stGCL: A versatile cross-modality fusion method based on multi-modal graph contrastive learning for spatial transcriptomics

Advances in spatial transcriptomics (ST) technologies have provided unprecedented opportunities to depict transcriptomic and histological landscapes in the spatial context. Multi-modal ST data provide abundant and comprehensive information about cellular status, function, and organization. However, in dealing with the processing and analysis of spatial transcriptomics data, existing algorithms struggle to effectively fuse the multi-modal information contained within ST data. Here, we propose a graph contrastive learning-based cross-modality fusion model named stGCL for accurate and robust integrating gene expression, spatial information as well as histological profiles simultaneously. stGCL adopts a novel histology-based Vision Transformer (H-ViT) method to effectively encode histological features and combines multi-modal graph attention auto-encoder (GATE) with contrastive learning to fuse cross-modality features. In addition, stGCL introduces a pioneering spatial coordinate correcting and registering strategy for tissue slices integration, which can reduce batch effects and identify cross-sectional domains precisely. Compared with state-of-the-art methods on spatial transcriptomics data across platforms and resolutions, stGCL achieves a superior clustering performance and is more robust in unraveling spatial patterns of biological significance. Additionally, stGCL successfully reconstructed three-dimensional (3D) brain tissue structures by integrating vertical and horizontal slices respectively. Application of stGCL in human bronchiolar adenoma (BA) data reveals intratumor spatial heterogeneity and identifies candidate gene biomarkers. In summary, stGCL enables the fusion of various spatial modality data and is a powerful tool for analytical tasks such as spatial domain identification and multi-slice integration.

bioinformatics↗

bioRxiv2023

E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation

E3 ubiquitin ligases are very important to regulate antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly Influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and H9N2, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-{beta} and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 showed a decreased susceptibility to H9N2 and PR8 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation levels of TBK1 and IRF3, downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator in controlling the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported. IMPORTANCEIAV is a significant zoonotic pathogen that causes infections of the respiratory system. Hosts have evolved multiple strategies to defend against IAV infection. However, not all host proteins play an active defense role. In this study, we found that the E3 ligase ASB3 regulates antiviral immunity by manipulating MAVS stability. Briefly, overexpression of ASB3 degrades MAVS, thereby promoting viral replication. In contrast, ASB3 deletion restores MAVS expression, upregulating IFN-I responses. Additional research revealed that ASB3 mediates the K48-linked polyubiquitination of MAVS at K297, resulting in ASB3 being degraded via the ubiquitin-proteasome pathway. These findings reveal, for the first time, a novel mechanism by which ASB3 negatively regulates antiviral immunity and provides a potential target for anti-IAV drug development.

immunology↗

bioRxiv2023

AhR ligands from LGG metabolites promote piglet intestinal ILC3 activation and IL-22 secretion to inhibit PEDV infection

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationship between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG (LGG) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3 cells and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor exerts its influence on various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, fostering their growth and development, suggesting a broad impact of AhR on intestinal health. In conclusion, our study demonstrates the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock.

immunology↗

bioRxiv2023

GABA(A) receptor activation drives GABARAP-Nix mediated autophagy to radiation-sensitize primary and brain-metastatic lung adenocarcinoma tumors

In non-small cell lung cancer (NSCLC) treatment, targeted therapies benefit only a subset of NSCLC, while radiotherapy responses are not durable and toxicity limits therapy. We find that a GABA(A) receptor activator, AM-101, impairs viability and clonogenicity of NSCLC primary and brain metastatic cells. Employing an ex vivo chip, AM-101 is as efficacious as the chemotherapeutic docetaxel, which is used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a survival benefit to mice bearing NSCLC intracranial tumors. GABA(A) receptor activation stimulates a selective-autophagic response via multimerization of GABA(A) Receptor-Associated Protein (GABARAP), stabilization of mitochondrial receptor Nix, and utilization of ubiquitin-binding protein p62. A targeted-peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis triggering autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity. HighlightsO_LIActivating GABA(A) receptors intrinsic to lung primary and metastatic brain cancer cells triggers a cytotoxic response. C_LIO_LIGABA(A) receptor activation works as well as chemotherapeutic docetaxel in impairing lung cancer viability ex vivo. C_LIO_LIGABA(A) receptor activation increases survival of mice bearing lung metastatic brain tumors. C_LIO_LIA selective-autophagic response is stimulated by GABA(A) receptor activation that includes multimerization of GABARAP and Nix. C_LIO_LIEmploying a new nanomolar affinity peptide that abrogates autophagosome formation inhibits cytotoxicity elicited by GABA(A) receptor activation. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/569295v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1df2f4eorg.highwire.dtl.DTLVardef@19ac26forg.highwire.dtl.DTLVardef@1533986org.highwire.dtl.DTLVardef@e59653_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

Middle-infrared Modulation Of Sleep By Cardiometabolic Function

The interdependence of sleep and overall well-being is profound. Sleep has the capacity to regulate hematopoiesis, thereby sustaining our physiological equilibrium. Nevertheless, our understanding regarding the potential reversibility of this regulatory process remains limited. In this study, we present evidence suggesting that exposure to middle-infrared radiation (MIR) within the 5-7 mm wavelength range can elicit non-thermal biological effects within the human body. These effects are characterized by an augmentation in blood circulation, mediated through modifications in red blood cell properties. Furthermore, MIR exposure is accompanied by a reduction in homocysteine levels and suppressor T-cell populations. Importantly, daytime modulation of MIR has been shown to significantly facilitate the amelioration of insomnia symptoms during nighttime, primarily through its impact on the architecture of deep sleep. Conclusively, our investigation reveals a robust association between cardiometabolic function and human sleep, with MIR presenting a promising avenue for enhancing sleep quality by regulating both the circulatory system and the immune system. These findings pave the way for the development of therapeutic strategies aimed at mitigating prevalent sleep-related disorders by disentangling the intricate links between sleep and cardiometabolic function.

physiology↗