Biology subjects

Fang, Z.

Publications and source records attributed to Fang, Z..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Endocytic dynamin deficiency impairs the host colonization of phytopathogenic fungi

During host-pathogen interactions, fungal pathogens exploit the endolysosomal trafficking network to fine-tune their responses to host and environmental stimuli, thereby facilitating disease progression. However, the molecular mechanisms underlying the fungal-specific functions of the endolysosomal network require further investigation. Here, we systematically characterized the endolysosomal network in Fusarium graminearum using the dynamin-like GTPase FgVps1 as an entry point. Functional analysis revealed that FgVps1 is essential for the release of retromer- and sorting nexin-associated vesicles from endosomes, thereby facilitating the trafficking of v-SNARE protein FgSnc1 and promoting fungal development and pathogenicity. Building on this, we further discovered that the retromer core subunit FgVps35 interacts with sorting nexin FgSnx4 and identified the corresponding interaction interface, which involves residues FgVps35N383 and FgSnx4E373. In addition, the ESCRT-II component FgVps36 bridges ESCRT-I and -III and interacts with both FgVps35 and FgSnx4, thereby preventing their mislocalization to the vacuole and maintaining endolysosomal trafficking. Notably, we demonstrated that inhibition of FgVps1 function, either by blocking its GTPase activity or by disrupting actin polymerization, effectively impaired endosomal trafficking and attenuates fungal pathogenicity. Altogether, our results uncover key mechanisms underlying the function of fungal endolysosomal network and providing a promising broad-spectrum strategy for controlling phytopathogenic fungi.

microbiology↗

bioRxiv2024

The penetration ring is a novel infection structure formed by the penetration peg for invading plant cell membrane in rice blast fungus

Many fungal pathogens develop specialized infection structures such as appressoria to penetrate plant cells. However, it is not clear whether special structures are formed after cell wall penetration before invading host plasma membrane in hemibiotrophic pathogens. Here, we showed that a penetration ring consisting of Ppe1 secreted proteins is formed after appressorium-mediated cell wall penetration and remained at the base of penetration site after invading plant plasma membrane by the rice blast fungus Magnaporthe oryzae. The same persistent Ppe1 ring is formed after the penetration of neighboring cells by transpressoria. PPE1 is specifically expressed during plant infection and the {Delta}ppe1 mutant is defective in penetration and invasive growth. Blockage of penetration peg formation impedes the development of the Ppe1 ring. Close examinations showed that the penetration ring is formed at the collar of penetration pegs between the plant cell wall and plasma membrane and it is persistent as a fixed ring even after invasive hyphae invaded neighboring cells. Furthermore, Ppe1 is a member of an expanded family of secreted proteins that are unique to fungal pathogens using extreme appressorium turgor for plant penetration. Other members of the Ppe1 family also localize to the penetration ring for anchoring on plasma membrane during plant infection. Taken together, a penetration ring consisting of a family of secreted proteins is formed between plant cell wall and plasma membrane, which may function as a novel physical structure at the interface between the tip of penetration pegs and plant plasma membrane before the differentiation of invasive hyphae. Significance StatementLike many other plant pathogens, the rice blast fungus forms melanized appressoria (specialized infection structures) to penetrate plant cells. In this study, we showed that a penetration ring is formed by penetration pegs after appressorium-mediated penetration of plant cell wall. This ring of secreted proteins is persistent at the point of penetration pegs invading plant plasma membrane to form invasive hyphae. Therefore, after the penetration of plant cell wall, the rice blast fungus forms a penetration ring that consists of a family of secreted proteins unique to pathogens using extreme appressorium turgor for penetration and may function as a physical structure for anchoring onto plant plasma membrane and developing invasive hyphae in penetrated cells.

pathology↗

bioRxiv2024

Structural insights into the in situ assembly of clustered protocadherin γB4

Clustered protocadherins (cPcdhs) belong to the cadherin superfamily and play important roles in neural development. cPcdhs can mediate homophilic adhesion and lead to self-avoidance and tiling by giving neurons specific identities in vertebrates. Structures and functions of cPcdhs have been studied extensively in the past decades, but the mechanisms behind the functions have not been fully understood. Here we investigate the in situ assembly of cPcdh-{gamma}B4, a member in the {gamma} subfamily of cPcdhs, by electron tomography and find that the full length cPcdh-{gamma}B4 does not show regular organization at the adhesion interfaces. By contrast, cPcdh-{gamma}B4 lacking the intracellular domain can generate an ordered zigzag pattern between cells and the cis interacting mode is different from the crystal packing of the ectodomain. We also identify the residues on the ectodomain that might be important for the zigzag pattern formation by mutagenesis. Furthermore, truncation mutants of the intracellular domain of cPcdh-{gamma}B4 reveal different assembly patterns between cell membranes, suggesting that the intracellular domain plays a crucial role in the intermembrane organization of cPcdh-{gamma}B4. Taken together, these results suggest both ectodomain and intracellular domain regulate the in situ assembly of cPcdh-{gamma}B4 at the adhesion interfaces, thereby providing mechanistic insights into the functional roles of cPcdhs during neuronal wiring.

biophysics↗

bioRxiv2024

Viscoelastic Extracellular Matrix Enhances Epigenetic Remodeling and Cellular Plasticity

Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function compared to those on purely elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility at cis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering.

cell biology↗

bioRxiv2024

Intracranial neural representation of phenomenal and access consciousness in the human brain

After more than 30 years of extensive investigation, impressive progress has been made in identifying the neural correlates of consciousness (NCC). However, the functional role of spatiotemporally distinct consciousness-related neural activity in conscious perception is debated. Based on empirical EEG findings, e.g., of the enhanced early negative wave and late positive wave under conscious conditions, an influential framework proposed that consciousness-related neural activities could be dissociated into two distinct processes: phenomenal and access consciousness. This framework has been supported mainly by comparison of neural activity between report and no-report paradigms; however, though hotly debated, its authenticity has not been examined in a single paradigm with more informative intracranial recordings. In the present study, we employed a novel visual awareness task and recorded the local field potential (LFP) of epilepsy patients with electrodes implanted in cortical and subcortical regions. Overall, we found that the latency of visual awareness-related activity exhibited a bimodal distribution, and the recording sites with short and long latencies were largely separated in location, except in the lateral prefrontal cortex (lPFC). The mixture of short and long latencies in the lPFC indicates that it plays a critical role in linking phenomenal and access consciousness. However, the division between the two is not as simple as the central sulcus, as proposed previously. Moreover, in 4 patients with electrodes implanted in the bilateral prefrontal cortex, early awareness-related activity was confined to the contralateral side, while late awareness-related activity appeared on both sides. Finally, Granger causality analysis showed that awareness-related information flowed from the early sites to the late sites. These results provide the first LFP evidence of neural correlates of phenomenal and access consciousness, which sheds light on the spatiotemporal dynamics of NCC in the human brain.

neuroscience↗

bioRxiv2024

Human intralaminar and medial thalamic nuclei transiently gate conscious perception through the thalamocortical loop

Human high-order thalamic nuclei have been known to closely correlate with conscious states. However, given the great difference of conscious states and contents (conscious perception), it is nearly unknown how those thalamic nuclei and thalamocortical interactions directly contribute to the transient process of conscious perception. To address this question, we simultaneously recorded local field potentials (LFP) in the human intralaminar, medial and ventral thalamic nuclei as well as in the prefrontal cortex (PFC), while patients with implanted electrodes performing a visual consciousness task. Overall, compared to the ventral nuclei, intralaminar and medial nuclei showed earlier and stronger consciousness-related activity. Moreover, the transient thalamocortical neural synchrony and cross-frequency coupling were both driven by the theta phase of the intralaminar and medial nuclei during conscious perception. These results indicated that the intralaminar and medial thalamic nuclei, rather than the commonly believed PFC, play a decisive gate role in conscious perception. Highlights O_LIIntralaminar and medial thalamic nuclei showed earlier and stronger visual consciousness-related activity, comparing to the ventral nuclei. C_LIO_LIIntralaminar and medial thalamic transiently drove the thalamocortical synchronization through theta (2-8Hz) phase modulation during the emergence of visual consciousness. C_LIO_LITheta phase of intralaminar and medial thalamic activity dynamically regulated the amplitude of PFC activity during the emergence of consciousness. C_LIO_LIIntralaminar and medial thalamic nuclei showed more regulation on lateral PFC than on other PFC subregions during the emergence of consciousness. C_LI

neuroscience↗

bioRxiv2024

Identification of a Conserved B-Cell Epitope on the Capsid Protein of Porcine Circovirus Type 4

Porcine circovirus type 4 (PCV4), a recently identified circovirus, is prevalent in numerous provinces in China, as well as in South Korea, Thailand, and Europe. PCV4 virus rescued from an infectious clone showed pathogenicity, suggesting the economic impact of PCV4. However, there remains a lack of understanding regarding the immunogenicity and epitopes of PCV4. This study generated a monoclonal antibody (MAb) 1D8 by immunizing mice with PCV4 virus-like particles (VLPs). Subsequently, the epitope recognized by the MAb 1D8 was identified by truncated protein expression and alanine scanning mutagenesis analysis. Results showed that the 225PKQG228 located at the C-terminus of the PCV4 Cap protein is the minimal motif binding to the MAb. Homology modeling analysis and immunoelectron microscopy revealed that the epitope extends beyond the outer surface of the PCV4 VLP. Moreover, the epitope is highly conserved among PCV4 strains and does not react with other PCVs. Together, the MAb 1D8 recognized epitope shows potential for detecting PCV4. These findings significantly contribute to the design of antigens for PCV4 detection and control strategies. IMPORTANCEPorcine circovirus type 4 (PCV4) is a novel circovirus. Although PCV4 has been identified in several countries, including China, Korea, Thailand, and Spain, no vaccine is available. Given the potential pathogenic effects of PCV4 on pigs, PCV4 could threaten the global pig farming industry, highlighting the urgency for further investigation. Thus, epitopes of PCV4 remain to be determined. Our finding of a conserved epitope significantly advances vaccine development and pathogen detection.

microbiology↗

bioRxiv2024

Metabolic Deficiencies Underlie Plasmacytoid Dendritic Cell Exhaustion After Viral Infection

Type I Interferons (IFN-I) are central to host protection against viral infections1. While any cell can produce IFN-I, Plasmacytoid Dendritic Cells (pDCs) make greater quantities and more varieties of these cytokines than any other cell type2. However, following an initial burst of IFN- I, pDCs lose their exceptional IFN-I production capacity and become "exhausted", a phenotype that associates with enhanced susceptibility to secondary infections3-5. Despite this apparent cost for the host, pDC exhaustion is conserved across multiple species and viral infections, but the underlying mechanisms and the potential evolutionary advantages are not well understood. Here we characterize pDC exhaustion and demonstrate that it is associated with a reduced capacity of pDCs to engage both oxidative and glycolytic metabolism. Mechanistically, we identify lactate dehydrogenase B (LDHB) as a novel positive regulator of pDC IFN-I production in mice and humans, show that LDHB deficiency is associated with suppressed IFN-I production, pDC metabolic capacity, and viral control following a viral infection, and demonstrate that preservation of LDHB expression is sufficient to partially restore exhausted pDC function in vitro and in vivo. Furthermore, restoring LDHB in vivo in exhausted pDCs increased IFNAR dependent infection- associated pathology. Therefore, our work identifies a novel and conserved mechanism for balancing immunity and pathology during viral infections, while also providing insight into the highly preserved but previously unexplained phenomenon of pDC exhaustion.

immunology↗

bioRxiv2024

Multi-gradient Permutation Survival Analysis Identifies Mitosis and Immune Signatures Steadily Associated with Cancer Patient Prognosis

The inconsistency of the association between genes and cancer prognosis is often attributed to many variables that contribute to patient survival. Whether there exist the Genes Steadily Associated with Prognosis (GEARs) and what their functions are remain largely elusive. Here we developed a novel method named "Multi-gradient Permutation Survival Analysis " (MEMORY) to screen the GEARs by using RNA-seq data from the TCGA database. We employed a network construction approach to identify hub genes from GEARs, and utilized them for cancer classification. In the case of lung adenocarcinoma (LUAD), the GEARs were found to be related to mitosis. Our analysis suggested that LUAD cell lines carrying PIK3CA mutations exhibit increased drug resistance. For breast invasive carcinoma (BRCA), the GEARs were related to immunity. Further analysis revealed that CDH1 mutation might regulate immune infiltration through the EMT process. Moreover, we explored the prognostic relevance of mitosis and immunity through their respective scores and demonstrated it as valuable biomarkers for predicting patient prognosis. In summary, our study offered significant biological insights into GEARs and highlights their potentials as robust prognostic indicators across diverse cancer types.

cancer biology↗

bioRxiv2024

Diaminopurine in Nonenzymatic RNA Template Copying

In the primordial RNA World, before the advent of ribozymes, nonenzymatic template copying would have been essential for the transmission of genetic information. However, the products of chemical copying with the canonical nucleotides are heavily biased towards the incorporation of G and C. Diaminopurine (D) can form a D:U base pair that is almost as strong as a G:C base pair. We therefore asked whether replacing A with D might lead to more efficient and less biased nonenzymatic template copying. As expected, primer extension substrates containing D bind to U in the template more tightly than substrates containing A. However, primer extension with D exhibited elevated reaction rates on a C template, leading to concerns about fidelity. To investigate the nature of the D:C mismatch, we solved the crystal structure of RNA duplexes containing D:C mismatches, and showed that D can form a wobble-type base pair with C. We then asked whether competition with G would decrease mismatched primer extension. We performed nonenzymatic primer extension with all four activated nucleotides on randomized RNA templates containing all four letters, and used deep sequencing to analyze the products. We found that the DUCG genetic system exhibited a more even product distribution and a lower mismatch frequency than the canonical AUCG system. Furthermore, primer extension is greatly reduced following all mismatches, including the D:C mismatch. Our study suggests that diaminopurine deserves further attention for its possible role in the RNA World, and as a potentially useful component of artificial nonenzymatic RNA replication systems.

biochemistry↗

bioRxiv2024

ATP13A1 engages GET3 to facilitate substrate-specific translocation

Proper localization of proteins to their final destinations is crucial for preserving cellular structure and functions. The interpretation and sorting of highly variable targeting sequences in secreted and membrane proteins, however, pose a challenge in achieving precise localization within specific secretory apparatus. In this study, we demonstrate that atypical signal sequences characterized by high hydrophobicity and/or the absence of characteristic charges undergo targeting to the endoplasmic reticulum (ER) in a reverse orientation, followed by partial cleavage. The P5A- ATPase ATP13A1 recognizes the cleaved signal sequence and dislocates it to the targeting factor GET3, subsequently engaging SEC61 for further translocation. Our findings unveil a comprehensive translocation pathway that operates in a substrate- specific manner, ensuring both high efficiency and fidelity in the protein subcellular localization.

biochemistry↗

bioRxiv2024

Intermittent energy restriction inhibits tumor growth and enhances paclitaxel response in a transgenic mouse model of endometrial cancer

ObjectiveOverweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential abilities of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC. MethodsLkb1fl/flp53fl/fl mice were fed high-fat diet (HFD) or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on HFD or switched to LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial tumor, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed. ResultsHFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment. ConclusionIn Lkb1fl/flp53fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as a EC prevention strategy in women with overweight/obesity.

cancer biology↗

bioRxiv2023

MOBFinder: a tool for MOB typing for plasmid metagenomic fragments based on language model

BackgroundMOB typing is a classification scheme that classifies plasmid genomes based on their relaxase gene. The host range of plasmids of different MOB categories are diverse and MOB typing is crucial for investigating the mobilization of plasmid, especially the transmission of resistance genes and virulence factors. However, MOB typing of plasmid metagenomic data is challenging due to the highly fragmented characteristic of metagenomic contigs. ResultsWe developed MOBFinder, an 11-class classifier to classify the plasmid fragments into 10 MOB categories and a non-mobilizable category. We first performed the MOB typing for classifying complete plasmid genomes using the relaxes information, and constructed the artificial benchmark plasmid metagenomic fragments from these complete plasmid genomes whose MOB types are well annotated. Based on natural language models, we used the word vector to characterize the plasmid fragments. Several random forest classification models were trained and integrated for predicting plasmid fragments with different lengths. Evaluating the tool over the benchmark dataset, MOBFinder demonstrates higher performance compared to the existing tool, with an overall accuracy of approximately 59% higher than the MOB-suite. Moreover, the balanced accuracy, harmonic mean and F1-score could reach 99% in some MOB types. In an application focused on a T2D cohort, MOBFinder offered insights suggesting that the MOBF type might accelerate the antibiotic resistance transmission in patients suffering from T2D. ConclusionsTo the best of our knowledge, MOBFinder is the first tool for MOB tying for plasmid metagenomic fragments. MOBFinder is freely available at https://github.com/FengTaoSMU/MOBFinder.

bioinformatics↗

bioRxiv2023

Genetic Discovery Enabled by A Large Language Model

Artificial intelligence (AI) has been used in many areas of medicine, and recently large language models (LLMs) have shown potential utility for clinical applications. However, since we do not know if the use of LLMs can accelerate the pace of genetic discovery, we used data generated from mouse genetic models to investigate this possibility. We examined whether a recently developed specialized LLM (Med-PaLM 2) could analyze sets of candidate genes generated from analysis of murine models of biomedical traits. In response to free-text input, Med-PaLM 2 correctly identified the murine genes that contained experimentally verified causative genetic factors for six biomedical traits, which included susceptibility to diabetes and cataracts. Med-PaLM 2 was also able to analyze a list of genes with high impact alleles, which were identified by comparative analysis of murine genomic sequence data, and it identified a causative murine genetic factor for spontaneous hearing loss. Based upon this Med-PaLM 2 finding, a novel bigenic model for susceptibility to spontaneous hearing loss was developed. These results demonstrate Med-PaLM 2 can analyze gene-phenotype relationships and generate novel hypotheses, which can facilitate genetic discovery.

genetics↗

bioRxiv2023

Structure of scavenger receptor SCARF1 and its interaction with lipoproteins

SCARF1 (Scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDL) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases.

biophysics↗

bioRxiv2023

A peptide-centric local stability assay to unveil protein targets of diverse ligands

While tremendous progress has been made in chemical proteomics for identifying protein-ligand interactions, it remains challenging for proteome-wide identification of ligand-binding regions without modifying the ligands. Here, we discovered that "disruptive trypsinization" amplifies the readout of ligand-induced protein local stability shifts, and explored this notion in developing "peptide-centric local stability assay" (PELSA), a modification-free approach which achieves unprecedented sensitivity in proteome-wide target identification and binding-region determination. We demonstrate the versatility of PELSA by investigating the interactions across various biological contexts including drug-target interactions, metabolism, epitope mapping, metal proteomics, and post-translational modification recognition. A PELSA study of the oncometabolite R2HG revealed functional insights about its targets and pathogenic processes in both cancer and immune cells. Thus, beyond offering users unprecedented sensitivity for characterizing diverse target-ligand interactions, PELSA supports informative screening and hypothesis generation studies throughout life science.

biochemistry↗

bioRxiv2023

One-pot virus detection based on isothermal amplificationcoupled with temperature-activated argonaute

Advances in programmable nucleases like CRISPR-associated protein (Cas) and Argonaute (Ago), combined with isothermal amplification, have made point-of-care testing (POCT) more accessible. However, the specific binding of the nuclease resulted in compatibility issues between the amplification and nuclease systems, substantially limiting the feasibility of a one-step workflow. Here, a temperature control solution based on immobilized thermotolerant Pyrococcus furiosus Ago (PfAgo) has been proposed. The use of immobilized PfAgo can effectively prevent interference with loop-mediated isothermal amplification (LAMP) at 65{degrees}C and accurately identifies amplicons when activated at 95{degrees}C. Following optimization, a sensitivity of 0.6 copies/L was achieved within 45 minutes, and high specificity was verified with no cross-reactivity among 22 other viruses. Additionally, the multiplex detection was designed for herpes virus sensing, with agreements of 86.4% for positive and 100% for negative samples. Our research presents an effective method for combining amplification and cleavage through the use of controllable nucleases, significantly improving the clinical applicability of diagnostic techniques dependent on programmable nucleases.

biochemistry↗

bioRxiv2023

Anti-adipogenic properties of clock activator chlorhexidine and a new derivative

BackgroundThe circadian clock exerts temporal control of metabolic pathways to maintain homeostasis, and its disruption leads to the development of obesity and insulin resistance. In adipose tissue, key regulators of clock machinery orchestrate adipogenic processes via the Wnt signaling pathway to impact mature adipocyte development. MethodsBased on the recent finding of chlorhexidine as a new clock activator, we determined its potential anti-adipogenic activities in distinct adipogenic progenitor models. Furthermore, we report the structural optimization of chlorhexidine leading to the discovery of analogs with improved efficacy in inhibiting adipogenesis. ResultsIn adipogenic progenitors with Per2::dLuc luciferase reporter, Chlorhexidine shortened clock period length with induction of core clock components. Consistent with its clock-activating function, Chlorhexidine robustly suppressed the lineage commitment and maturation of adipogenic mesenchymal precursors, with comparable effect on inhibiting preadipocyte terminal differentiation. Mechanistically, we show that Chlorhexidine induces signaling components of the Wnt pathway resulting in activation of Wnt activity. Via modification of its chemical scaffold, we generated analogs of chlorhexidine that led to the identification of CM002 as a new clock- activating molecule with improved anti-adipogenic activity. ConclusionsCollectively, our findings uncovered the anti-adipogenic functions of a new class of small molecule clock activators. These compounds provide novel chemical probes to dissect clock function in maintaining metabolic homeostasis and may have therapeutic implications in obesity and associated metabolic disorders.

cell biology↗