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Zhuang, H.

Publications and source records attributed to Zhuang, H..

At least 19 recordsLinked to original sources

A single cortical circuit implements fast and slow visual search

How the brain produces different behaviors from a fixed anatomical substrate is a foundational question in neuroscience. The dominant account holds that behavioral flexibility requires distinct neural circuits: dedicated systems selectively recruited for different processing modes. An alternative proposes that flexibility arises not from switching between circuits, but from dynamically controlling the speed at which a shared circuit operates. Here, we test this account directly using intracranial EEG recordings from nineteen human patients performing two visual search tasks of markedly different difficulty: an easy color-singleton search and a difficult orientation search, a fast vs. slow dissociation attributed for four decades to distinct anatomical and oscillatory neural systems. We show that both search tasks recruit the same cortical regions, oscillatory frequencies, and processing hierarchy. Dynamic time warping reveals that the two neural trajectories are time-stretched versions of one another; the same temporal scaling appears within each condition between faster and slower trials, indexing response speed rather than the distinction between tasks. Alpha-band oscillations (~8-10 Hz) support this temporal scaling through two coordinated mechanisms: synchronizing activity across a posterior cortical network and phase-gating local high-frequency activity (70-150 Hz) within those regions at the same preferred phase in both conditions. These findings establish that, for the two tasks studied here, fast and slow visual search are not implemented by selecting between distinct dedicated circuits, but by adjusting the speed of a single alpha-coordinated architecture. The same principle may apply to other search tasks, and to other domains in which dual-process architectures have been invoked, a testable prediction for future studies.

neuroscience↗

Whole-genome duplication drives biosynthetic gene cluster fragmentation and regulatory rewiring of monoterpene indole alkaloid metabolism in Strychnos

Whole-genome duplications (WGDs) reshape plant genomes by generating redundancy, after which lineage-specific architectures emerge through fractionation, gene loss and rearrangement. How specialized metabolic pathways remain functionally integrated after such large-scale restructuring remains poorly understood. This problem is especially relevant for biosynthetic gene clusters (BGCs), which physically organize specialized-metabolism genes yet can be disrupted by post-duplication rearrangement. Here, we present the first chromosome-level genomes for Loganiaceae, including near telomere-to-telomere assemblies of Strychnos ignatii and S. pubescens, together with a draft genome of the extinct species S. ridleyi. Following a lineage-specific WGD, the two extant Strychnos species evolved contrasting genome-evolutionary trajectories and metabolite profiles: S. ignatii shows expansion of monoterpenoid- and monoterpene indole alkaloid (MIA)-associated gene families and strychnine-type MIA dominance, whereas S. pubescens exhibits elevated transposable element activity associated with DNA-binding with one finger (DOF)-linked regulatory rewiring and broader sesquiterpenoid- and triterpenoid-rich chemistry. Crucially, both species retain active strychnine biosynthesis despite fragmentation of a deeply conserved alkaloid BGC in MIA-producing Gentianales, revealing how pathway function can persist after disruption of ancestral BGC architecture. Comparative metabolomic and transcriptomic pathway analyses indicate norfluorocurarine oxidase (NO) as a major divergence point associated with strychnine accumulation. Promoter analyses, yeast one-hybrid assays, and electrophoretic mobility shift assays support a model in which S. ignatii retains the canonical jasmonate-responsive MYB, MYC2/bHLH, and AP2/ERF cis-regulatory module at NO, whereas the orthologous S. pubescens promoter shows reduced capacity to recruit these activators and instead exhibits a DOF-associated architecture. Together, our results show that WGD can decouple physical cluster architecture from pathway function, allowing specialized metabolic pathways to remain active while divergent chemical phenotypes evolve through lineage-specific combinations of coding-space expansion and transposable-element-associated cis-regulatory rewiring.

evolutionary biology↗

Halo: a pretrained model for whole-cell segmentation from nuclei images in spatial transcriptomics

Spatial transcriptomics enables measurement of gene expression while preserving spatial organization within tissues. Accurate reconstruction of single-cell transcriptomes requires precise whole-cell segmentation, yet many spatial transcriptomics experiments provide only nuclear staining images, making reliable inference of cell boundaries difficult. Here we introduce Halo, a pretrained segmentation model that reconstructs whole-cell boundaries by integrating nuclear morphology with the spatial distribution of RNA transcripts. Halo converts transcript coordinates into molecular density maps that are processed jointly with DAPI images using a Cellpose-SAM segmentation architecture. Unlike existing approaches that require dataset-specific training, Halo is pretrained on multimodal Xenium data from 12 tissue types and can be directly applied to new datasets without additional training. Across diverse tissues, Halo substantially outperforms the widely used nuclear expansion strategy, achieving higher agreement with ground-truth cell boundaries and more accurate RNA-to-cell assignment. Improved segmentation leads to more reliable cell type identification and more accurate estimation of cell morphological features. By providing a pretrained, generalizable model for whole-cell reconstruction, Halo enables scalable and reproducible cell segmentation for image-based spatial transcriptomics.

bioinformatics↗

Structural insights on the ligand selectivity of the mouse trace amine-associated receptor TAAR7e

Trace amine-associated receptors (TAARs), a subclass of G protein-coupled receptors involved in detecting volatile amines, are co-expressed with odorant receptors in the main olfactory epithelium. Although many behaviorally relevant amines have been identified for olfactory TAARs, the molecular mechanisms underlying their selectivity for amines with varying carbon chain lengths and degrees of amine substitution remain unclear. In this study, we used mTAAR7e as a model to investigate these mechanisms. Homology modeling revealed a conserved ligand-binding pocket, supported by sequence-structure covariance analysis across TAARs. Structure-activity relationship profiling revealed key chemical determinants integral to mTAAR7e-mediated odorant recognition and provided, for the first time, a structural explanation for its selective preference toward longer carbon chains and tertiary amines. Computationally predicted interactions between mTAAR7e and the representative ligand N,N-dimethylcyclohexylamine (DMCHA) were validated through site-directed mutagenesis. Furthermore, conformational dynamics of mTAAR7e during receptor activation were characterized, providing insights into activation-related structural rearrangements. Together, these findings offer novel insights into the molecular logic of TAAR ligand selectivity and may advance our understanding of how TAARs mediate both olfactory and systemic aminergic signaling.

molecular biology↗

Scientifically Uninformed Legislation System Undermines Ecological Sustainability of the Yangtze River

Legal frameworks typically aim to protect environmental systems through regulations, treaties, and conservation measures. However, without scientifically informed enforcement, these policies may inadvertently exacerbate environmental degradation, particularly when addressing complex socio-environmental issues. We reviewed the development of Chinas environmental legislation related to ecosystem protection in the Yangtze River watershed and evaluated its effectiveness by analyzing illegal fishing cases from 2015 to 2021, prosecuted under Chinas Environmental Public Interest Litigation framework. Our findings reveal that court-ordered fish release remedies often undermine, rather than support, the sustainability of the Yangtze River ecosystem. This is primarily due to mismatches between the taxonomic identity of illegally caught fishes and those specified for release, species misidentification, and a bias toward economically valuable species in court-ordered release decisions. These unintended discrepancies between environmental protection goals and actual ecological outcomes underscore the need to integrate scientific expertise into legal practice to enhance the sustainability of socio-environmental systems.

ecology↗

The hollow truth: ethylene-triggered ROS, PCD, senescence, and autophagy drive hollow stem formation

Hollow stems have independently evolved multiple times across the plant kingdom, and play crucial roles in plant development and various environmental adaptations. However, the mechanisms underlying stem hollowness remain poorly understood. Water spinach (Ipomoea aquatica) is one of the few hollow-stemmed plants in the Convolvulaceae family, and its hollow stems are essential for thriving in aquatic environments. Using histochemical staining and transcriptome analysis, we identified programmed cell death (PCD) is involved in cavity formation of water spinach shoot tips. Single-cell transcriptome analysis further revealed that ethylene and reactive oxygen species (ROS) drive and regulate this process by activating transcription factors IaNAC074, IaNAC087, IaNAC029, IaNTL9, and IaTGA9, which initiate PCD, senescence, and autophagy, collectively controlling cell death. These findings were validated through treatments with ethylene and ROS reagents in water spinach and transient expression in tobacco. Additionally, transcriptomic data suggest that these mechanisms may also play a role in hollow stem formation in bamboo, highlighting the conservation of PCD regulatory mechanisms in plant development. This work not only fills a major knowledge gap in the adaptive mechanisms of hollow stem formation but also opens new avenues for agricultural and ecological applications, offering strategies to enhance crop tolerance to flooding and accelerate crop growth.

plant biology↗

High-resolution imaging atlas reveals context-dependent role of pancreatic sympathetic innervation in diabetic mice

Gaining a better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in islets of adult WT and diabetic mice. Our data shows that more than [~]30% /{beta}-cells are innervated by sympathetic nerves in both WT and diabetic mice. Also, sympathetic innervated /{beta}-cells are reduced in DIO mice, whereas sympathetic innervated {beta}-cells are increased in db/db mice. Besides, in situ chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in WT and db/db mice, but decreases in DIO mice. In situ cPSD also enhances insulin sensitivity in diabetic mice without affecting WT mice. Overall, our findings advance our comprehension of diabetes by highlighting the distinctive impact of pancreatic sympathetic innervation on glucose regulation. HighlightsPancreatic sympathetic innervation plays an important role in glucose homeostasis. In our study, we systematically investigate sympathetic innervation in the islets of WT and diabetic mice. O_LI45.9% -cells and 31.8% {beta}-cells are innervated by sympathetic nerves in 10-week-old WT mice. C_LIO_LISympathetic innervated /{beta}-cells are reduced in DIO mice, whereas sympathetic innervated {beta}-cells are increased in db/db mice. C_LIO_LIUnlike the core-mantle structure observed in WT and DIO mice, -cells and {beta}-cells are intermixed in db/db mice. C_LIO_LIPancreatic sympathetic denervation elicits varied responses across diabetic models, where it improves glucose tolerance and insulin sensitivity in db/db mice, yet it increases insulin sensitivity but reduces glucose tolerance in DIO mice. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/623708v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@183be78org.highwire.dtl.DTLVardef@4dc76borg.highwire.dtl.DTLVardef@5f5ca0org.highwire.dtl.DTLVardef@ba3cc7_HPS_FORMAT_FIGEXP M_FIG Summary of morphological and physiological phenotypes in diabetic mice. All data are normalized to that of WT-10 mice. The numbers of "+" refer to their relative numbers. {uparrow} or {downarrow} refers to increase or decrease, ns refers to "not significant". "-" refers to the experiment has not been carried out. C_FIG

neuroscience↗

Trajectory-guided dimensionality reduction for multi-sample single-cell RNA-seq data reveals biologically relevant sample-level heterogeneity

The analysis of single-cell RNA-sequencing (scRNA-seq) data with multiple biological samples remains a pressing challenge. We present MUSTARD, a trajectory-guided dimension reduction method for multi-sample multi-condition scRNA-seq data. This all-in-one decomposition reveals major gene expression variation patterns along the trajectory and across multiple samples simultaneously, providing opportunities to discover sample endotypes along with associated genes and gene modules. In data-driven simulation, MUSTARD achieves high accuracy in distinguishing sample-level group differences that existing methods fail to capture. MUSTARD also demonstrates a robust ability to capture gene markers and pathways associated with phenotypes of interest across multiple real-world case studies.

bioinformatics↗

MEK1/2 and ERK1/2 mediated lung endothelial injury and altered hemostasis promote diffuse alveolar hemorrhage in murine lupus

ObjectiveAbout 3% of lupus patients develop severe diffuse alveolar hemorrhage (DAH) with pulmonary vasculitis. B6 mice with pristane-induced lupus also develop DAH, but BALB/c mice are resistant. DAH is independent of TLR signaling and other inflammatory pathways. This study examined the role of the mitogen-activated protein kinase pathway (MEK1/2-ERK1/2, JNK, p38). MethodsB6 and BALB/c mice were treated with pristane {+/-} inhibitors of MEK1/2 (trametinib/GSK1120212, "GSK"), ERK1/2 (SCH772984, "SCH"), JNK, or p38. Effects on lung hemorrhage and hemostasis were determined. ResultsGSK and SCH abolished DAH, whereas JNK and p38 inhibitors were ineffective. Apoptotic cells were present in lung from pristane-treated mice, but not mice receiving pristane+GSK and endothelial dysfunction was normalized. Expression of the ERK1/2-regulated transcription factor Egr1 increased in pristane-treated B6, but not BALB/c, mice and was normalized by GSK. Pristane also increased expression of the anticoagulant genes Tfpi (tissue factor pathway inhibitor) and Thbd (thrombomodulin) in B6 mice. The ratio of tissue factor (F3) to Tfpi increased in B6 (but not BALB/c) mice and was normalized by GSK. Circulating Thbd protein increased in B6 mice and returned to normal after GSK treatment. Consistent with augmented endothelial anticoagulant activity, pristane treatment increased tail bleeding in B6 mice. ConclusionPristane treatment promotes lung endothelial injury and DAH in B6 mice by activating the MEK1/2-ERK1/2 pathway and impairing hemostasis. The hereditary factors determining susceptibility to lung injury and bleeding in pristane-induced lupus are relevant to the pathophysiology of life-threatening DAH in SLE and may help to optimize therapy.

immunology↗

PreTSA: computationally efficient modeling of temporal and spatial gene expression patterns

Modeling temporal and spatial gene expression patterns in large-scale single-cell and spatial transcriptomics data is a computationally intensive task. We present PreTSA, a method that offers computational efficiency in modeling these patterns and is applicable to single-cell and spatial transcriptomics data comprising millions of cells. PreTSA consistently matches the results of state-of-the-art methods while significantly reducing computational time. PreTSA provides a unique solution for studying gene expression patterns in extremely large datasets.

bioinformatics↗

A bacterial type III effector hijacks plant ubiquitin proteases to evade degradation

Gram-negative bacterial pathogens inject effector proteins inside plant cells using a type III secretion system. These effectors manipulate plant cellular functions and suppress the plant immune system in order to promote bacterial proliferation. Despite the fact that bacterial effectors are exogenous threatening proteins potentially exposed to the protein degradation systems inside plant cells, effectors are relative stable and able to perform their virulence functions. In this work, we found that RipE1, an effector protein secreted by the bacterial wilt pathogen, Ralstonia solanacearum, undergoes phosphorylation of specific residues inside plant cells, and this promotes its stability. Moreover, RipE1 associates with plant ubiquitin proteases, which contribute to RipE1 deubiquitination and stabilization. The absence of those specific phosphorylation sites or specific host ubiquitin proteases leads to a substantial decrease in RipE1 protein accumulation, indicating that RipE1 hijacks plant post-translational modification regulators in order to promote its own stability. These results suggest that effector stability or degradation in plant cells constitute another molecular event subject to co-evolution between plants and pathogens.

plant biology↗

m6A RNA methylation impairs gene expression variability and reproductive thermotolerance in Arabidopsis

Plants are more susceptible to high temperature stress during reproductive development, which can cause drastic yield loss of fruit and seed crops. Unfortunately, the underlying mechanism remains largely unknown. Here we suggest that m6A RNA methylation level increases in the reproductive tissues of Arabidopsis and negatively regulates gene expression variability. It has been suggested that stochasticity of gene expression can be advantageous to fitness of living organisms under environmental challenges. Indeed, reduced gene expression variability in flowers was associated with compromised transcriptional activation of heat-responsive genes. Importantly, disruption of an RNA demethylase AtALKBH10B led to lower gene expression variability, hypo-responsiveness of heat-activated genes, and strong reduction of plant fertility. Overall, our work proposes a novel mechanism that m6A RNA modification mediates the bet-hedging strategy of plants challenged by heat stress.

plant biology↗

Two subsets of circulating Ly6Clo monocytes distinguished by CD138 (syndecan-1) expression and Nr4a1 dependence in pristane-treated mice

Chronic peritoneal inflammation following pristane injection induces lupus with diffuse alveolar hemorrhage (DAH) and pulmonary capillaritis in C57BL/6 mice. The pathogenesis involves pristane-induced microvascular lung injury. BALB/c mice are resistant to endothelial injury and DAH. Lung disease in C57BL/6 mice is abolished by depleting monocytes/macrophages. The objective of this study was to define the role of myeloid subsets in DAH. Hemorrhage and vasculitis were abolished in Ccr2-/- mice, indicating involvement of bone marrow-derived monocytes/macrophages. Along with Ly6Chi monocytes, we found two subsets of circulating Ly6Clo monocytes: one CD138- and a novel CD138+ subset. Nr4a1-dependent patrolling Ly6Clo monocytes maintain vascular integrity after endothelial injury. Circulating Ly6CloCD138+ monocytes were associated with DAH and were absent in mice without DAH. They also were absent in Nr4a1-/- mice, whereas Ly6CloCD138- monocytes were unaffected. However, Nr4a1-/- mice were susceptible to pristane-induced DAH and lung vasculitis, suggesting that disease onset does not require Ly6CloCD138- monocytes. Peritoneal Ly6CloCD138+ M{phi} were unchanged in Nr4a1-/- mice, indicating that they are not derived from Ly6CloCD138+ monocytes. We conclude that pristane-induced lung microvascular lung injury stimulates a wave of Nr4h1-dependent Ly6CloCD138+ patrolling monocytes in an ineffectual effort to maintain vascular integrity in the face of ongoing endothelial damage.

immunology↗

Inhibition of SAR S-CoV-2 infection and replication by lactoferrin, MUC1 and α-lactalbumin identified in human breastmilk

The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to the public health. Human breastmilk is an extremely complex with nutritional composition to nourish infants and protect them from different kinds of infection diseases and also SARS-CoV-2 infection. Previous studies have found that breastmilk exhibited potent antiviral activity against SARS-CoV-2 infection. However, it is still unknown which component(s) in the breastmilk is responsible for its antiviral activity. Here, we identified Lactoferrin (LF), MUC1 and -Lactalbumin (-LA) from human breastmilk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and in vitro confirmation that inhibited SARS-CoV-2 infection and analyzed their antiviral activity using the SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP) in the Huh7.5, Vero E6 and Caco-2-N cell lines. Additionally, we found that LF and MUC1 could inhibit viral attachment, entry and post-entry replication, while -LA just inhibit viral attachment and entry. Importantly, LF, MUC1 and -LA possess potent antiviral activities towards not only wild-type but also variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.1 (kappa). Moreover, LF from other species (e.g., bovine and goat) is still capable of blocking viral attachment to cellular heparan sulfate. Taken together, our study provided the first line of evidence that human breastmilk components (LF, MUC1 and -LA) are promising therapeutic candidates warranting further development or treatingVID-19 given their exceedingly safety levels.

microbiology↗

findPC: An R package to automatically select number of principal components in single-cell analysis

SummaryPrincipal component analysis (PCA) is widely used in analyzing single-cell genomic data. Selecting the optimal number of PCs is a crucial step for downstream analyses. The elbow method is most commonly used for this task, but it requires one to visually inspect the elbow plot and manually choose the elbow point. To address this limitation, we developed six methods to automatically select the optimal number of PCs based on the elbow method. We evaluated the performance of these methods on real single-cell RNA-seq data from multiple human and mouse tissues. The perpendicular line method with 20 PCs has the best overall performance, and its results are highly consistent with the numbers of PCs identified manually. We implemented the six methods in an R package, findPC, that objectively selects the number of PCs and can be easily incorporated into any automatic analysis pipeline. Availability and ImplementationfindPC R package is freely available at https://github.com/haotian-zhuang/findPC Contactzhicheng.ji@duke.edu Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells

Since the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several somatic cells, little is known about the infection of SASRS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that SARS-CoV-2 pseudovirus and GX_P2V could infect lung progenitor and even anterior foregut endoderm cells causing these cells death, which differentiated from human embryonic stem cells (hESCs). The infection and replication of SARS-CoV-2 and GX_P2V were inhibited when treated with whey protein of breastmilk and Remdesivir, confirming that these two viruses could infect lung progenitor and even anterior foregut endoderm. Moreover, we found that SARS-CoV-2 pseudovirus could infect endoderm and ectoderm. We found that whey protein blocked SARS-CoV-2 infecting these cells. In line with the SARS-CoV-2 results, GX_P2V could also infected endoderm and ectoderm, and also was inhibited by Remdesivir treatment. Although expressing coronavirus related receptor such as ACE2 and TMPRSS2, mesoderm cells are not permissive for SARS-CoV-2 and GX_P2V infection, which needed further to study the mechanisms. Interestingly, we also found that hESCs, which also express ACE2 and TMPRSS2 markers, are permissive for GX_P2V but not SARS-CoV-2 pseudovirus infection and replication, indicating the widespread cell types for GX_P2V infection. Heparin treatment blocked efficiently viral infection. These results provided insight that these stem cells maybe provided a stable repository of coronavirus function or genome. The potential consequence of SARS-CoV-2 and animal coronavirus such as GX_P2V infection in hESCs, germ layer and induced progenitors should be closely monitored.

microbiology↗

The effect of whey protein on viral infection and replication of SARS-CoV-2 and pangolin coronavirus in vitro

Since the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human breastmilk, little is known about the antiviral property of human breastmilk to SARS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that whey protein from human breastmilk effectively inhibited both SARS-CoV-2 and GX_P2V by blocking viral attachment, entry and even post-entry viral replication. Moreover, human whey protein inhibited infectious virus production proved by the plaque assay. We found that whey protein from different species such as cow and goat also showed anti-coronavirus properties. And commercial bovine milk also showed similar activity. Interestingly, the main antimicrobial components of breastmilk, such as Lactoferrin and IgA antibody, showed limited anti-coronavirus activity, indicating that other factors of breastmilk may play the important anti-coronavirus role. Taken together, we reported that whey protein inhibits SARS-CoV-2 and its related virus of GX_P2V. These results rule out whey protein as a direct-acting inhibitor of SARS-CoV-2 and GX_P2V infection and replication and further investigation of its molecular mechanism of action in the context of COVID-19.

microbiology↗

Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue

Aerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) platform. Interaction of aerobic capacity and aging was studied via regression analysis. Our results showed at young age, metabolites linked to amino acid metabolism differed in serum and muscle with aerobic capacity, whereas no difference were observed in WAT. In aged animals, most prominent changes in metabolites occurred in WAT. Aerobic capacity and aging interactively affected seven metabolites linked to energy metabolism. Our results support previous findings that high aerobic capacity is associated with more efficient amino acid metabolism in muscle. While impaired branched chain amino acids (BCAAs) and fatty acid metabolism in the muscle may associate to the high risk of metabolic disorders and shorter lifespan previously observed in LCRs. The interactive effects of aging and aerobic capacity on energy metabolism-related metabolites were largely driven by HCRs, reflecting the importance of inherited aerobic capacity in the aging process. Our results highlight that dysfunctional mitochondrial {beta}-oxidation in WAT may be one key mechanism related to aging.

molecular biology↗