Biology subjects

Zhou, D.

Publications and source records attributed to Zhou, D..

At least 127 records · Page 7Linked to original sources

bioRxiv2023

Sterile Soil as Prebiotics Mitigate Intergenerational Loss of Gut Microbial Diversity and Anxiety-Like Behavior Induced by Antibiotics in mice

The decline in gut microbial diversity of modern human is closely associated with the rising prevalence of various diseases. It is imperative to investigate the underlying causes of gut microbial loss and the rescue measures. Although the impact of non-perinatal antibiotic use on gut microbiota has been recognized, its intergenerational effects remain unexplored. Our previous research has highlighted soil in the farm environment as a key prebiotic for gut microbiome health by restoring gut microbial diversity and balance. In this study, we investigated the intergenerational consequences of antibiotic exposure and the therapeutic potential of soil prebiotics. We treated mice with vancomycin and streptomycin for 2 weeks continuously, followed by 4-8 weeks of withdrawal period before breeding. The process was repeated across 3 generations. Half of the mice in each generation received an oral soil prebiotic intervention. We assessed gut microbial diversity, anxiety behavior, microglia reactivity, and gut barrier integrity across generations. The antibiotics exposure led to a decrease in gut microbial diversity over generations, along with aggravated anxiety behavior, microglia abnormalityies, and altered intestinal tight junction protein expression. Notably, the third generation of male mice exhibited impaired reproductive capacity. Oral sterile soil intervention restored gut microbial diversity in adult mice across generations, concomitantly rescuing abnormalities in behavior, microglia activity, and intestinal barrier integrity. In conclusion, this study simulated an important process of the progressive loss gut microbiota diversity in modern human and demonstrated the potential of sterile soil as a prebiotic to reverse this process. The study provides a theoretical and experimental basis for the research and therapeutic interventions targeting multiple modern chronic diseases related to intestinal microorganisms.

microbiology↗

bioRxiv2023

Identification of a novel MCR-1 variant displaying low level of co-resistance to β-lactam antibiotics that uncovers a potential novel antimicrobial peptide

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. It is accepted that MCR-1 affects bacterial fitness, and this fitness cost correlates with bacterial membrane lipid A perturbation. However, the detailed molecular mechanism remains unclear. Here, we screened out a novel MCR-1 variant, named M6, with a two-point mutation that rendered a low level of co-resistance to {beta}-lactam antibiotics. Compared to wild-type (WT) MCR-1, this variant caused severe lipid A perturbation resulting in peptidoglycan layer remodelling and thus resulted in phenotypic co-resistance to {beta}-lactams. Moreover, we found that a lipid A loading cavity is localized at the linker domain of MCR-1 and governs colistin resistance and bacterial membrane permeability, and the mutated pocket of M6 facilitates the binding affinity of lipid A. More importantly, synthetic peptides derived from M6 achieved broad-spectrum antimicrobial activity. These findings provide insights into a potential vulnerability that could be exploited in future antimicrobial drug design.

microbiology↗

bioRxiv2023

Quantitative relations among causality measures with applications to pulse-output nonlinear network reconstruction

The causal connectivity of a network is often inferred to understand the network function. It is arguably acknowledged that the inferred causal connectivity relies on the causality measure one applies, and it may differ from the networks underlying structural connectivity. However, the interpretation of causal connectivity remains to be fully clarified, in particular, how causal connectivity depends on causality measures and how causal connectivity relates to structural connectivity. Here, we focus on nonlinear networks with pulse signals as measured output, e.g., neural networks with spike output, and address the above issues based on four intensively utilized causality measures, i.e., time-delayed correlation coefficient, time-delayed mutual information, Granger causality, and transfer entropy. We theoretically show how these causality measures are related to one another when applied to pulse signals. Taking the simulated Hodgkin-Huxley neural network and the real mouse brain network as two illustrative examples, we further verify the quantitative relations among the four causality measures and demonstrate that the causal connectivity inferred by any of the four well coincides with the underlying network structural connectivity, therefore establishing a direct link between the causal and structural connectivity. We stress that the structural connectivity of networks can be reconstructed pairwise without conditioning on the global information of all other nodes in a network, thus circumventing the curse of dimensionality. Our framework provides a practical and effective approach for pulse-output network reconstruction. Significance StatementInferring network connectivity is a key challenge in many diverse scientific fields. We investigate networks with pulse signal as measured output and solve the above reverse-engineering issue by establishing a direct link between the networks causal connectivity and structural connectivity. Here, the causal connectivity can be inferred by any one of the four causality measures, i.e., time-delayed correlation coefficient, time-delayed mutual information, Granger causality, and transfer entropy. We analytically reveal the relationship among these four measures and show that they are equally effective to fully reconstruct the network connectivity pairwise. Our work provides a practical framework to reconstruct the structural connectivity in general pulse-output nonlinear networks or subnetworks.

neuroscience↗

bioRxiv2023

Calponin 2 harnesses metabolic reprogramming to determine kidney fibrosis

In the fibrotic kidneys, the extent of a formed deleterious microenvironment is determined by cellular mechanical forces. This process requires metabolism for energy; however, how cellular mechanics and metabolism are connected remains unclear. Our proteomics revealed that actin filament binding and cell metabolism are the two most dysregulated events in the fibrotic kidneys. As a prominent actin stabilizer, Calponin 2 (CNN2) is predominantly expressed in fibroblasts and pericytes. CNN2 knockdown preserves kidney function and alleviates fibrosis. Global proteomics profiled that CNN2 knockdown enhanced the activities of the key rate-limiting enzymes and regulators of fatty acid oxidation (FAO) in diseased kidneys. Inhibiting carnitine palmitoyltransferase 1 in the FAO pathway results in lipid accumulation and extracellular matrix deposition in the fibrotic kidneys, which were restored after CNN2 knockdown. In patients, increased serum CNN2 levels are correlated with lipid content. Bioinformatics and chromatin immunoprecipitation showed that CNN2 interactor, estrogen receptor 2 (ESR2) binds peroxisome proliferator-activated receptor- (PPAR) to transcriptionally regulate FAO downstream target genes expression amid kidney fibrosis. In vitro, ESR2 knockdown repressed the mRNA levels of PPAR and the key genes in the FAO pathway. Conversely, activation of PPAR reduced CNN2-induced matrix inductions. Our results suggest that balancing cell mechanics and metabolism is crucial to develop therapeutic strategies to halt kidney fibrosis.

pathology↗

bioRxiv2022

STING-dependent cytosolic DNA sensing pathway drives the progression to leukemia in TET2-mutated HSPCs

Somatic loss-of-function mutations of the dioxygenase Ten-eleven translocation-2 (TET2) occur frequently in individuals with clonal hematopoiesis (CH) and acute myeloid leukemia (AML). These common hematopoietic disorders can be recapitulated in mouse models. However, the underlying mechanisms by which the deficiency in TET2 promotes these disorders remain largely unknown. Here we show that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated to mediate the effect of TET2 deficiency in leukemogenesis in mouse models. DNA damage arising in Tet2-deficient hematopoietic stem/progenitor cells (HSPCs) leads to activation of the cGAS-STING pathway which in turn induces the development of CH and myeloid transformation. Notably, both pharmacological inhibition and genetic deletion of STING suppresses Tet2 mutation-induced aberrant myelopoiesis. In patient-derived xenograft (PDX) models, STING inhibition specifically attenuates the proliferation of leukemia cells from TET2-mutated individuals. These observations suggest that the hematopoietic transformation associated with TET2 mutations is powered through sterile inflammation dependent on the activated cGAS-STING pathway, and that STING may represent a potential target for intervention of relevant hematopoietic malignancies. Key pointsO_LITet2 deficiency leads to DNA damage which in turn activates the cGAS-STING pathway to induce an inflammatory response C_LIO_LIBlocking STING in TET2-mutated hematopoietic stem/progenitor cells suppresses clonal hematopoiesis in mice and leukemogenesis in patient-derived xenograft models C_LI

cancer biology↗

bioRxiv2022

Compression supports low-dimensional representations of behavior across neural circuits

Dimensionality reduction, a form of compression, can simplify representations of information to increase efficiency and reveal general patterns. Yet, this simplification also forfeits information, thereby reducing representational capacity. Hence, the brain may benefit from generating both compressed and uncompressed activity, and may do so in a heterogeneous manner across diverse neural circuits that represent low-level (sensory) or high-level (cognitive) stimuli. However, precisely how compression and representational capacity differ across the cortex remains unknown. Here we predict different levels of compression across regional circuits by using random walks on networks to model activity flow and to formulate rate-distortion functions, which are the basis of lossy compression. Using a large sample of youth (n = 1, 040), we test predictions in two ways: by measuring the dimensionality of spontaneous activity from sensorimotor to association cortex, and by assessing the representational capacity for 24 behaviors in neural circuits and 20 cognitive variables in recurrent neural networks. Our network theory of compression predicts the dimensionality of activity (t = 12.13, p < 0.001) and the representational capacity of biological (r = 0.53, p = 0.016) and artificial (r = 0.61, p < 0.001) networks. The model suggests how a basic form of compression is an emergent property of activity flow between distributed circuits that communicate with the rest of the network.

neuroscience↗

bioRxiv2022

KDM5A/B promotes HIV-1 latency and KDM5 inhibitors promote HIV-1 lytic reactivation

Combinational antiretroviral therapy (cART) effectively suppresses HIV-1 infection, replication, and pathogenesis in HIV-1 patients. However, the patients HIV-1 reservoir still cannot be eliminated by current cART or other therapies. One putative HIV-1 eradication strategy is "shock and kill", which reactivates HIV-1 in latently-infected cells and induces their cytopathic effect or immune clearance to decrease the patients reservoir size. KDM5A and KDM5B act as the HIV-1 latency-promoting genes, decreasing the HIV-1 viral gene transcription and reactivation in infected cells. Depletion of KDM5 A/B by siRNA knockdown (KD) increases H3K4 trimethylation (H3K4me3) in HIV-1 Tat-mediated transactivation. We also found that the KDM5-specific inhibitor JQKD82 can increase H3K4me3 at the HIV-1 LTR region during HIV-1 reactivation and induce cytopathic effects. We applied the JQKD82 in combination with the non-canonical NF-{kappa}B activator AZD5582, which synergistically induced HIV-1 reactivation and cell apoptosis in HIV-1 infected cells. These results suggested that the KDM5 inhibition can be a putative HIV-1 latency-reversing strategy for the HIV-1 "shock and kill" eradication therapy.

microbiology↗

bioRxiv2022

Methadone alters transcriptional programs associated with synapse formation in human cortical organoids

Opioid use disorder (OUD) among pregnant women has become an epidemic in the United States. Pharmacological interventions for OUD involve methadone, a synthetic opioid analgesic that attenuates withdrawal symptoms and behaviors linked with maternal drug abuse. However, methadones ability to readily accumulate in neural tissue, and cause long-term neurocognitive sequelae, has led to concerns regarding its effect on prenatal brain development. We took advantage of human cortical organoid (hCO) technology to probe how this drug impacts the earliest mechanisms giving rise to the cerebral cortex. To this end, we conducted bulk mRNA sequencing of 2-month-old hCOs derived from two cell lines that were chronically treated with a clinically relevant dose of 1M methadone for 50 days. Differential expression and gene ontology analyses revealed a robust transcriptional response to methadone associated with functional components of the synapse, the underlying extracellular matrix (ECM), and cilia. Further unsupervised co-expression network and predictive protein-protein interaction analyses demonstrated that these changes occurred in concert, centered around a regulatory axis consisting of growth factors, developmental signaling pathways, and matricellular proteins. Our results demonstrate that exposure to methadone during early cortico-genesis fundamentally alters transcriptional programs associated with synapse formation, and that these changes arise by modulating extra-synaptic molecular mechanisms in the ECM and cilia. These findings provide novel insight into methadones putative effect on cognitive and behavioral development and a basis for improving interventions for maternal opioid addiction.

neuroscience↗

bioRxiv2022

A frameshift in Yersinia pestis rcsD leads to expression of a small HPt variant that alters canonical Rcs signalling to preserve flea-mammal plague transmission cycles

Multiple genetic changes in the enteric pathogen Yersinia pseudotuberculosis have driven the emergence of Yesinia pestis, the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenisation of rcsA, encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating Y. pestis flea-borne transmission. Additionally, rcsD, another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this rcsD mutation resulted in predominant production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and low levels of full-length RcsD. Genetic analysis revealed that the rcsD frameshift mutation followed the emergence of rcsA pseudogenisation. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the pgm locus in modern lineages of Y. pestis. Taken together, our findings suggest that a frameshift mutation in rcsD, is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.

microbiology↗

bioRxiv2022

FGFR1 governs iron metabolism via regulating post-translational modification of IRP2 in prostate cancer cells

The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression. However, how FGFR1 facilitates PCa progression is not fully revealed, although it is known to confer tumor growth advantage and metastasis. Here we report that FGFR1 deletion in DU145 human PCa cells retards the iron metabolism and reduces transferrin receptor 1 (TFR1), which synergistically enhances the anti-cancer effect of iron chelator. FGFR1 and TFR1 are highly expressed in PCa, and FGFR1 overexpression increased TFR1 in PCa cell lines. Furthermore, we first time demonstrate that FGFR1 deletion boosts and shifts the degradation of iron regulatory proteins 2 (IRP2) to downregulate TFR1. Detailed characterization revealed that based on FGFR1 deletion the stability of IRP2 is broken, whose degradation is accelerated, which can be not observed without FGFR1 deletion. In addition, IRP2 overexpression rescue the malignancy degree of DU145 cells. Our results here unravel a novel mechanism by which FGFR1 promotes PCa progression by upregulating iron metabolism, and that the FGFR1/IRP2/TFR1 axis can be a potential target for managing PCa progression.

cancer biology↗

bioRxiv2022

Cell division history encodes directional information of fate transitions

Single-cell RNA-sequencing (scRNA-seq) enables systematic mapping of cellular differentiation trajectories. However, inferring the cell-fate transitions under diseases or perturbations is still challenging due to the high cellular plasticity. Here, we demonstrate that monotonically expressed genes (MEGs) along cell divisions record the directions of state transitions regardless of the cellular processes. We developed a computational framework (PhyloVelo) to identify MEGs and reconstruct a novel transcriptomic velocity field by leveraging both scRNA-seq and phylogenetic information. PhyloVelo accurately recovered linear, bifurcated and convergent differentiations in simulations and C. elegans. It outperformed current approaches for delineating cellular trajectories in embryo development and tumor evolution through analysis of five CRISPR/Cas9-based lineage tracing datasets. Together, our study unveils an internal cellular clock and provides a powerful method for cellfate analysis in diverse biological contexts.

genomics↗

bioRxiv2022

DEED: A Dataset for Dream-related Emotion Research

Emotion is closely related to human cognition and behaviour. In recent years, scholars have conducted extensive research on emotion in waking state based on electroencephalography (EEG) and achieved certain results. However, Emotional activity continues after sleep, with a concentrated response of sleep emotions in dreams. Sleep emotions are concentrated in dreams, which can better reflect a series of real physical and psychological states of the human body. Currently, there is no publicly available dataset for the assessment of dream mood. Therefore, we present a physiological dataset Dream Emotion Evaluation Dataset (DEED) for the assessment of dream mood, which recorded EEG signals from 38 participants over 89 whole sleep nights and 533 dream segments(after exclusion of unqualified nights, those dream segments are extracted from 82 whole sleep nights). We studied the correlations between the subjective ratings and the EEG signals and brain network patterns for dream emotions. In addition, the relationship between the asymmetry of left and right brain bands and positive and negative dream emotions was studied. The machine learning algorithm was also used to classify different emotional EEG, which confirmed the validity of the dataset. In the meantime, we encourage other researchers to explore the underlying neural mechanisms involved in sleep.

neuroscience↗

bioRxiv2022

Co-targeting BCL-XL and MCL-1 with DT2216 and AZD8055 synergistically inhibits small-cell lung cancer growth without causing on-target toxicities in mice

Small-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. The dismal prognosis in SCLC is in part associated with an upregulation of BCL-2 family anti-apoptotic proteins, including BCL-XL and MCL-1. Unfortunately, the currently available inhibitors of BCL-2 family anti-apoptotic proteins, except BCL-2 inhibitors, are not clinically relevant because of various on-target toxicities. We, therefore, aimed to develop an effective and safe strategy targeting these anti-apoptotic proteins with DT2216 (our platelet-sparing BCL-XL degrader) and AZD8055 (an mTOR inhibitor) to avoid associated on-target toxicities while synergistically optimizing tumor response. Through BH3 mimetic screening, we identified a subset of SCLC cell lines that is co-dependent on BCL-XL and MCL-1. After screening inhibitors of selected tumorigenic pathways, we found that AZD8055 selectively downregulates MCL-1 in SCLC cells and its combination with DT2216 synergistically killed BCL-XL/MCL-1 co-dependent SCLC cells, but not normal cells. Mechanistically, the combination caused BCL-XL degradation and suppression of MCL1 expression, and thus disrupted MCL-1 interaction with BIM leading to an enhanced apoptotic induction. In vivo, DT2216+AZD8055 combination significantly inhibited the growth of cell line-derived and patient-derived xenografts and reduced tumor burden accompanied with extended survival in a genetically-engineered mouse (GEM) model of SCLC without causing significant thrombocytopenia or other normal tissue injury. Thus, these preclinical findings lay a strong foundation for future clinical studies to test DT2216+mTOR inhibitor combination in a subset of SCLC patients whose tumors are co-driven by BCL-XL and MCL-1.

cancer biology↗

bioRxiv2022

Molecular mechanism of substrate recognition by folate transporter SLC19A1

Folate (vitamin B9) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe diseases. Notably, mammalian cells lack the ability to de novo synthesize folate but instead rely on its intake from extracellular sources via specific transporters or receptors, among which SLC19A1 is the ubiquitously expressed one in tissues. However, the mechanism of substrate recognition by SLC19A1 has been unclear. Here we report the cryo-EM structures of human SLC19A1 and its complex with 5-methyltetrahydrofolate at 3.5-3.6 [A] resolution and elucidate the critical residues for substrate recognition. In particular, we reveal that two variant residues among SLC19 subfamily members would designate the specificity for folate. Moreover, we identify intracellular thiamine pyrophosphate as the favorite coupled substrate for folate transport by SLC19A1. Together, this work has established the molecular basis of substrate recognition by this central folate transporter.

biochemistry↗

bioRxiv2022

IL-22/IL-22RA1 promotes human Tenon's capsule fibroblasts proliferation and regulates fibrosis through STAT3 signaling pathway

The study is aimed to investigate that the IL-22/IL-22RA1 signaling pathway regulates scar formation. A total of 31 glaucoma patients who had been previously treated with trabeculectomy surgery and the intraocular pressure was uncontrollable because of scarring and 19 strabismus patients as control patient group. ELISA showed that the IL-22 content of serum from glaucoma patients was 29.80{+/-}5.1 ng/l which is higher than that 5.21{+/-}0.9 ng/l from healthy group significantly. Serum from patients was used to incubate human Tenons capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and western blot result showed that IL-22 mediates the biological function of HTFs cells via binding IL-22RA1 directly. When transfection of siR-IL-22RA1 or IL-22RA1 gene, the HTFs cells shown significantly anti-fibrosis or pro-fibrosis separately. By using STAT3 inhibitor BAY in IL-22RA1 overexpression group, IL-22-induced proliferation were reduced in HTFS cells. IL-22 promoted fibroblasts cell proliferation and -SMA via IL-22/IL-22RA1/STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis. This results also show the novel factor in process of postoperative scarring. Summary StatementThe present study suggested that IL-22 expression in glaucoma patient after surgery. IL-22/IL-22RA1 signaling pathway promoted fibroblasts cell proliferation and -SMA by activating the STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis.

cell biology↗

bioRxiv2022

Structural basis of a high-affinity antibody binding to glycoprotein region with consecutive glycosylation sites

Consecutive glycosylation sites occur in both self and viral proteins. Glycan-shielding of underneath peptide region is a double-edged sword, that avoids immune attack to self-proteins, but helps viruses including HIV-1 and SARS-CoV2 to escape antibody binding. Here we report a high-affinity antibody, 16A, binding to linear peptide containing consecutive glycosylation sites. Co-crystallization of 16A Fab and glycopeptides with GalNAc modifications at different sites showed that STAPPAHG is the sequence recognized by 16A antibody. GalNAc modification at Threonine site on STAPPAHG sequence significantly increased the affinity of Fab binding by 30.6 fold (KD=6.7nM). The increased affinity is conferred by hydrophilic and pi-stacking interactions between the GalNAc residue on Threonine site and a Trp residue from the CDR1 region of the heavy chain. Furthermore, molecular modeling suggested that GalNAc on T site causes more favorable conformation for antibody binding. These results showed that glycan modification most proximal to linear peptide core epitope significantly increases antigenicity of a glycopeptide epitope. The antibody recognition mode by peptide-binding CDR groove with a glycan-binding edge, may shed light on designing of linear glycopeptide-based vaccines for cancer and viral diseases. TeaserA high-affinity antibody was found to bind densely glycosylated glycoprotein region by a peptide binding groove of the antibodys variant region, with a glycan-binding edge specific to glycosylation site most proximal to core peptide epitope.

immunology↗

bioRxiv2022

Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2

Some COVID-19 patients are unable to clear their infection or are at risk of severe disease, requiring treatment with neutralising monoclonal antibodies (nmAb) and/or antivirals. The rapid roll-out of novel therapeutics means there is limited understanding of the likely genetic barrier to drug resistance. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to the detection of emerging drug resistance. Here we report the accrual of mutations in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the epitopes of the respective nmAbs. For casirivimab+imdevimab these are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.

genetics↗

bioRxiv2022

Fatty acid binding protein 1 and fatty acid synthetase overexpression have differential effects on collagen III and cross-linking in Zongdihua pig tissues

The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in Zongdihua pigs. We wished to identify processes affecting meat quality using molecular genetics to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were overexpressed from recombinant plasmids. Our sequence analysis of the cloned genes indicated that FABP1 gene encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane region. FAS encodes 333 amino acid hydrophobic protein containing with 26 phosphorylation sites and 0 transmembrane regions. The basal levels of FABP1 and FAS in pig tissues expression were 3 -3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) overexpression of FAS resulted in significantly increased expression of COL3A1 gene (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) overexpression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P < 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, enhancing FABP1 expression increases collagen accumulation and this preliminarily suggests that FAS and FABP1 can serve as fat-related candidate genes providing a theoretical basis for the study of fat deposition in Zongdihua pigs.

animal behavior and cognition↗