Biology subjects

He, J.

Publications and source records attributed to He, J..

At least 217 records · Page 12Linked to original sources

bioRxiv2024

Deep learning modeling of ribosome profiling reveals regulatory underpinnings of translatome and interprets disease variants

Gene expression involves transcription and translation. Despite large datasets and increasingly powerful methods devoted to calculating genetic variants effects on transcription, discrepancy between mRNA and protein levels hinders the systematic interpretation of the regulatory effects of disease-associated variants. Accurate models of the sequence determinants of translation are needed to close this gap and to interpret disease-associated variants that act on translation. Here, we present Translatomer, a multimodal transformer framework that predicts cell-type-specific translation from mRNA expression and gene sequence. We train Translatomer on 33 tissues and cell lines, and show that the inclusion of sequence substantially improves the prediction of ribosome profiling signal, indicating that Translatomer captures sequence-dependent translational regulatory information. Translatomer achieves accuracies of 0.72 to 0.80 for de novo prediction of cell-type-specific ribosome profiling. We develop an in silico mutagenesis tool to estimate mutational effects on translation and demonstrate that variants associated with translation regulation are evolutionarily constrained, both within the human population and across species. Notably, we identify cell-type-specific translational regulatory mechanisms independent of eQTLs for 3,041 non-coding and synonymous variants associated with complex diseases, including Alzheimers disease, schizophrenia, and congenital heart disease. Translatomer accurately models the genetic underpinnings of translation, bridging the gap between mRNA and protein levels, and providing valuable mechanistic insights toward mapping "missing regulation" in disease genetics.

genomics↗

bioRxiv2024

Ilamycins are dual inhibitors of ClpX and ClpC1 involved in proteostasis in Mycobacteria

The mycobacterial caseinolytic protease (Clp) system has been recognized as a promising therapeutic target. In this study, we identified two novel ilamycin analogs, ilamycin E (ILE) and ilamycin F (ILF), both targeting the ClpC1 component of the ClpC1P1P2 proteasome. ILE potently disrupts ClpC1P1P2-mediated proteolysis, leading to delayed bactericidal activity, while ILF also binds ClpC1, albeit with lower affinity. Notably, we discovered a unique mutation in clpX and a novel insertion in clpC1, both conferring resistance to ILE and ILF in mycobacterium, validated by gene editing. Furthermore, ILE can also inhibit the proteolytic activity of ClpXP1P2 in a manner dependent on the substrates tag sequence and adaptor. This first demonstration of clpX- and clpC1-mediated ilamycin resistance underscores the potential of ilamycins to target multiple components of the Clp protease system, offering a novel dual-target strategy for combating mycobacterial infections.

microbiology↗

bioRxiv2024

EmbB and EmbC Regulate the Sensitivity of Mycobacterium abscessus to Echinomycin

Treatment of Mycobacterium abscessus (Mab) infection is a major challenge due to its intrinsic resistance to most available drugs. It is thus imperative to find new anti-Mab drugs. In this study, we investigated the activity and intrinsic resistance mechanism of echinomycin (ECH) against Mab. ECH is active against Mab (MIC: 2 {micro}g/mL). The embC gene knockout strain (Mab{Delta}embC) showed hyper-sensitive to ECH (MIC: 0.0078-0.0156 {micro}g/mL). The MICs of ECH-resistant strains screened based on the Mab{Delta}embC strain were 0.25-1 {micro}g/mL. Mutations were found in the EmbB, including Asp306Ala, Asp306Asn, Arg350Gly, Val555Ile, and Gly581Ser, which led to increased resistance to ECH when overexpressed in Mab{Delta}embC individually (0.25-0.5 {micro}g/mL). The EmbB mutants edited by the CRISPR/Cpf1 system became more resistant to ECH (MIC: 0.25-0.5 {micro}g/mL). The permeability of gene-edited and overexpressed Mab strains was reduced, as shown by the ethidium bromide accumulation assay, but it was still significantly higher than that of the parent Mab. To summarize, our study demonstrates that ECH has a strong anti-Mab activity and confirms that EmbB and EmbC are related to the sensitivity of Mab to ECH. EmbB mutation may partially compensate for the function of EmbC. Impact StatementMycobacterium abscessus (Mab) is a rapidly growing, intrinsic multidrug-resistant Mycobacterium. This study demonstrated that echinomycin (ECH) has potent antibacterial activity against Mab, and the mechanism of ECH resistance to Mab is related to EmbB and EmbC. EmbB and EmbC can alter the sensitivity of Mab to ECH by altering the permeability of its cell wall. In addition, there is a functional complementary evolution between EmbB and EmbC to regulate sensitivity to ECH. Overall, our study provides a novel anti-Mab drug candidate ECH and a scientific foundation for developing effective strategies to prevent and control Mab.

microbiology↗

bioRxiv2024

Convergent evolution of plant prickles is drivenby repeated gene co-option over deep time

An enduring question in evolutionary biology concerns the degree to which episodes of convergent trait evolution depend on the same genetic programs, particularly over long timescales. Here we genetically dissected repeated origins and losses of prickles, sharp epidermal projections, that convergently evolved in numerous plant lineages. Mutations in a cytokinin hormone biosynthetic gene caused at least 16 independent losses of prickles in eggplants and wild relatives in the genus Solanum. Strikingly, homologs promote prickle formation across angiosperms that collectively diverged over 150 million years ago. By developing new Solanum genetic systems, we leveraged this discovery to eliminate prickles in a wild species and an indigenously foraged berry. Our findings implicate a shared hormone-activation genetic program underlying evolutionarily widespread and recurrent instances of plant morphological innovation.

evolutionary biology↗

bioRxiv2024

STING contributes to pulmonary hypertension by targeting the interferon and BMPR2 signaling through regulating F2RL3

Rational/ObjectivesPulmonary hypertension (PH) is an incurable disease characterized by pulmonary arterial remodeling. Endothelial injury and inflammation are the key triggers of the disease initiation. Recent findings suggest that STING (stimulator of interferon genes) activation plays a critical role in the endothelial dysfunction and interferon signaling. Here, we investigated the involvement of STING in the pathogenesis of PH. MethodsPH patients and rodent PH model samples, Sugen5416/hypoxia (SuHx) PH model, and pulmonary artery endothelial cells (PAECs) were used to evaluate the hypothesis. Measurement and Main ResultsThe cyclic GMP-AMP (cGAS)-STING signaling pathway was activated in the lung tissues from rodent PH models and PH patients, and the TNF- induced PAECs in vitro. In particular, STING significantly elevated in the endothelial cell in PH disease settings. In SuHx mouse model, genetic knockout or pharmacological inhibition of STING prevented the progression of PH. Functionally, knockdown of STING reduced the proliferation and migration in PAECs. Mechanistically, STING transcriptional regulates its binding partner F2RL3 through STING-NF-{kappa}B axis, which activated the interferon signaling and repressed the BMPR2 signaling both in vitro and in vivo. Further analysis revealed that F2RL3 expression was increased in PH settings and identified negative feedback regulation of F2RL3/BMPR2 signaling. Accordingly, a positive correlation of expression levels between STING and F2RL3/ interferon-stimulated genes (ISGs) was observed in vivo. ConclusionsOur findings suggest that STING activation in PAECs plays a critical role in the pathobiology of PH. Targeting STING may be a promising therapeutic strategy for preventing the development of PH.

cell biology↗

bioRxiv2024

Arsinothricin Biosynthesis Involving a Noncanonical Radical SAM Enzyme for C-As Bond Formation

Arsinothricin is a potent antibiotic secreted by soil bacteria. The biosynthesis of Arsinothricin was proposed to involve two steps. The first step is C-As bond formation between trivalent As and the 3-amino-3-carboxypropyl (ACP) group of S-adenosyl-L-methionine (SAM), which is catalyzed by the protein ArsL. However, the reaction has not been verified in vitro, and ArsL has not been characterized in detail. Interestingly, ArsL contains a CxxxCxxC motif and thus belongs to the radical SAM enzyme superfamily, the members of which cleave SAM and generate a 5'-deoxyadenosyl radical. Here, we found that ArsL cleaves the C{gamma},Met-S bond of SAM and generates an ACP radical that resembles Dph2, a noncanonical radical SAM enzyme involved in diphthamid biosynthesis. As Dph2 does not contain the CxxxCxxC motif, ArsL is a unique noncanonical radical SAM enzyme that contains this motif but generates an ACP radical. Together with the methyltransferase ArsM, we successfully reconstituted arsinothricin biosynthesis in vitro. ArsL has a conserved RCCLKC motif in the C-terminal sequence and belongs to the RCCLKC-tail radical SAM protein subfamily. By truncation, we showed that this motif binds to the substrate arsenite and is highly important for its activity. Our results suggested that ArsL is a noncanonical radical SAM enzyme with a canonical radical SAM enzyme motif, implying that more noncanonical radical SAM chemistry may exist within the radical SAM enzyme superfamily. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=40 SRC="FIGDIR/small/577332v1_ufig1.gif" ALT="Figure 1"> View larger version (8K): org.highwire.dtl.DTLVardef@14547e2org.highwire.dtl.DTLVardef@172753eorg.highwire.dtl.DTLVardef@16f4a99org.highwire.dtl.DTLVardef@18ab4c8_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

Endogenous labeling empowers accurate detection of m6A from single long reads of direct RNA sequencing

Although plenty of machine learning models have been developed to detect m6A RNA modification sites using the electric current signals of ONT direct RNA sequencing (DRS) reads, the landscape of m6A on different RNA isoforms is still a mystery due to their limited capacity to distinguish the m6A on individual long reads and RNA isoforms. The primary challenge in training the model with single-read accuracy is the difficulty of obtaining the training data from individual DRS reads that comprehensively represent the m6A on endogenous RNAs. Here, we endogenously label the methylated m6A sites on single ONT DRS reads by APOBEC1-YTH induced C-to-U mutations, strategically positioned 10-100 nt away from the known m6A sites on the same reads. Adopting a semi-supervised leaning strategy, we obtain 700,438 reliable 5-mer single-read level m6A signals, providing a comprehensive representation of m6A on endogenous RNAs. Leveraging this dataset, we develop m6Aiso, a deep residual neural network model that not only accurately identifies and quantifies known m6A sites but also reveals unknown, subtly methylated m6A sites responsive to METTL3 depletion. Analyzing m6Aiso-determined m6A on single reads and isoforms uncovers distance-dependent linkages of m6A sites along single molecules, as well as differential methylation of identical m6A sites on different isoforms. Moreover, we find wide-spread functionally important dynamic changes of m6A sites on specific isoforms during epithelial-mesenchymal transition (EMT). The pivotal utilization of the endogenous labeling strategy empowers m6Aiso to achieve remarkable precision in pinpointing m6A on individual molecules, underscores its effectiveness in elucidating the intricate dynamics and complexities of m6A across RNA isoforms.

bioinformatics↗

bioRxiv2024

Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2

The cardiovascular system generates and responds to mechanical forces. The heartbeat pumps blood through a network of vascular tubes, which adjust their caliber in response to the hemodynamic environment. However, how endothelial cells in the developing vascular system integrate inputs from circulatory forces into signaling pathways to define vessel caliber is poorly understood. Using vertebrate embryos and in vitro-assembled microvascular networks of human endothelial cells as models, flow and genetic manipulations, and custom software, we reveal that Plexin-D1, an endothelial Semaphorin receptor critical for angiogenic guidance, employs its mechanosensing activity to serve as a crucial positive regulator of the Dorsal Aortas (DA) caliber. We also uncover that the flow-responsive transcription factor KLF2 acts as a paramount mechanosensitive effector of Plexin-D1 that enlarges endothelial cells to widen the vessel. These findings illuminate the molecular and cellular mechanisms orchestrating the interplay between cardiovascular development and hemodynamic forces. HighlightsO_LIPlexin-D1 mechanosensing of blood flow tunes the caliber of the Dorsal Aorta (DA) C_LIO_LIThe DA widens without raising endothelial cell numbers, which can change separate from the caliber C_LIO_LIThe Kruppel-like transcription factor 2 (KLF2) is a key Plexin-D1 mechano-effector during development C_LIO_LIKLF2 increases endothelial cell size to expand the DA caliber C_LI

developmental biology↗

bioRxiv2024

Self-inspired learning to denoise for live-cell super-resolution microscopy

Every collected photon is precious in live-cell super-resolution (SR) fluorescence microscopy for contributing to breaking the diffraction limit with the preservation of temporal resolvability. Here, to maximize the utilization of accumulated photons, we propose SN2N, a Self-inspired Noise2Noise engine with self-supervised data generation and self-constrained learning process, which is an effective and data-efficient learning-based denoising solution for high-quality SR imaging in general. Through simulations and experiments, we show that the SN2Ns performance is fully competitive to the supervised learning methods but circumventing the need for large training-set and clean ground-truth, in which a single noisy frame is feasible for training. By one-to-two orders of magnitude increased photon efficiency, the direct applications on various confocal-based SR systems highlight the versatility of SN2N for allowing fast and gentle 5D SR imaging. We also integrated SN2N into the prevailing SR reconstructions for artifacts removal, enabling efficient reconstructions from limited photons. Together, we anticipate our SN2N and its integrations could inspire further advances in the rapidly developing field of fluorescence imaging and benefit subsequent precise structure segmentation irrespective of noise conditions.

bioengineering↗

bioRxiv2024

Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy

Tumor-associated macrophages (TAMs) are a crucial factor in reprogramming the tumor microenvironment following radiotherapy. The mechanisms underlying this process remain to be elucidated. Here, we seek to investigate the effects of hypofractionated radiotherapy on macrophages dynamics in a subcutaneous Lewis lung carcinoma murine model. Utilizing single-cell RNA sequencing, we identified a distinct M2-like population of macrophages with high Ccl8 expression level post-hypofractionated radiotherapy. Remarkbly, hypofractionated radiotherapy promoted CCL8high macrophages infiltration and reprogrammed them by upregulating immunosuppressive genes and downregulating antigen-presenting genes, leading to an immunosuppressive tumor microenvironment. Further, we demonstrated that hypofractionated radiotherapy amplified the CCL signaling pathway, enhancing the pro-tumorigenic functions of CCL8high macrophages and promoting macrophages recruitment. The combination therapy of hypofractionated radiotherapy with the CCL signal inhibitor Bindarit was effective in reducing M2 macrophages infiltration and extending the duration of local tumor control. This research highlights the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

immunology↗

bioRxiv2024

BLADE-ON-PETIOLE interacts with CYCLOIDEA to fine-tune CYCLOIDEA-mediated flower symmetry in Monkeyflowers (Mimulus)

AbstractMorphological novelties, or key innovations, are instrumental to the diversification of the organisms. In plants, one such innovation is the evolution of zygomorphic flowers, which is thought to promote outcrossing and increases flower morphological diversity. We isolated three allelic mutants from two Mimulus species displaying altered floral symmetry and identified the causal gene as the orthologue of Arabidopsis BLADE-ON-PETIOLE. We found that MlBOP and MlCYC2a physically interact and this BOP-CYC interaction module is highly conserved across the angiosperms. Furthermore, MlBOP self-ubiquitinates and suppresses MlCYC2a self- activation. MlCYC2a, in turn, impedes MlBOP ubiquitination. Thus, this molecular tug-of-war between MlBOP and MlCYC2a fine-tunes the expression of MlCYC2a, contributing to the formation of bilateral symmetry flowers, a key trait in angiosperm evolution. One Sentence SummaryMolecular tug-of-war between MlBOP and MlCYC2a fine-tunes the expression of MlCYC2a, contributing to the bilateral flower symmetry formation.

developmental biology↗

bioRxiv2024

Tractography-based automated identification of the retinogeniculate visual pathway with novel microstructure-informed supervised contrastive learning

The retinogeniculate visual pathway (RGVP) is responsible for carrying visual information from the retina to the lateral geniculate nucleus. Identification and visualization of the RGVP are important in studying the anatomy of the visual system and can inform the treatment of related brain diseases. Diffusion MRI (dMRI) tractography is an advanced imaging method that uniquely enables in vivo mapping of the 3D trajectory of the RGVP. Currently, identification of the RGVP from tractography data relies on expert (manual) selection of tractography streamlines, which is time-consuming, has high clinical and expert labor costs, and is affected by inter-observer variability. In this paper, we present a novel deep learning framework, DeepRGVP, to enable fast and accurate identification of the RGVP from dMRI tractography data. We design a novel microstructure-informed supervised contrastive learning method that leverages both streamline label and tissue microstructure information to determine positive and negative pairs. We propose a simple and successful streamline-level data augmentation method to address highly imbalanced training data, where the number of RGVP streamlines is much lower than that of non-RGVP streamlines. We perform comparisons with several state-of-the-art deep learning methods that were designed for tractography parcellation, and we show superior RGVP identification results using DeepRGVP. In addition, we demonstrate a good generalizability of DeepRGVP to dMRI tractography data from neurosurgical patients with pituitary tumors and we show DeepRGVP can successfully identify RGVPs despite the effect of lesions affecting the RGVPs. Overall, our study shows the high potential of using deep learning to automatically identify the RGVP.

neuroscience↗

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

EMformer: Transformer-Based Isotropic Reconstruction for Volume Electron Microscopy

Volume electron microscopy (vEM) has become a rapidly developing technique for studying the 3D architecture of biological specimens, such as cells, tissues, and organs at nanometer resolution; this technique involves collecting a series of electron micrographs of axial sequential sections and reconstructing the 3D volume, providing useful information on the cellular ultrastructural spectrum. This technique currently suffers from anisotropic resolution between the lateral (x, y) and axial (z) directions and the loss/damage of sections. Here, we develop a new algorithm, IsoVEM, based on a video transformer model to boost the axial resolution and achieve isotropic reconstruction of vEM. By learning high-resolution axial structures and utilizing the 3D continuity of biological structures, IsoVEM can recover axial information and repair random lost/damaged sections based on a self-supervision strategy, achieving a higher resolution than existing methods, which has been validated for both simulated FIB-SEM datasets and experimental ssTEM datasets. In addition to visual validation, the segmentation efficiency and statistical precision of various ultrastructures, e.g., neurons, mitochondria, vesicles, and membrane bilayers, also prove the better performance of IsoVEM. Therefore, using IsoVEM, we achieve isotropic reconstruction via anisotropic axial sampling, which increases the vEM throughput for studying large-scale biological architectures.

biophysics↗

bioRxiv2023

Whole genome association testing in 333,100 individuals across three biobanks identifies rare non-coding single variant and genomic aggregate associations with height

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N=200,003), TOPMed (N=87,652) and All of Us (N=45,445). We performed rare (<0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal, intergenic and deep-intronic annotation. We observed 29 independent variants associated with height at P < 6 x 10-10 after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed a novel approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

genetics↗

bioRxiv2023

Photobodies enable the phase-separation and counterbalance of phytochrome B mediated PIF5 degradation and stabilization

Photoactivation of the plant photoreceptor and thermosensor phytochrome B (PHYB) triggers its condensation into subnuclear photobodies (PBs). However, the function of PBs remains frustratingly elusive. Here, we found that PHYB recruits PHYTOCHROME-INTERACTING FACTOR5 (PIF5) to PBs. Surprisingly, PHYB exerts opposing roles in degrading and stabilizing PIF5. Perturbing PB size by overproducing PHYB provoked a biphasic PIF5 response: while a moderate increase in PHYB enhanced PIF5 degradation, further elevating the PHYB level stabilized PIF5 by retaining more of it in enlarged PBs. These results reveal a PB-mediated light and temperature sensing mechanism, in which PHYB condensation confers the co-occurrence and competition of two antagonistic phase-separated PHYB signaling actions--PIF5 stabilization in PBs and PIF5 degradation in the surrounding nucleoplasm-- thereby enabling an environmentally-sensitive counterbalancing mechanism to titrate nucleoplasmic PIF5 and its transcriptional output. This PB-enabled signaling mechanism provides a framework for regulating a plethora of PHYB-interacting signaling molecules in diverse plant environmental responses.

plant biology↗

bioRxiv2023

A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally-scalable analytical pipeline for functionally-informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in 61,861 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered new associations with lipid traits missed by single-trait analysis, including rare variants within an enhancer of NIPSNAP3A and an intergenic region on chromosome 1.

genetics↗

bioRxiv2023

Adipokinetic hormone signaling mediates the fecundity of Diaphorina citri infected by Candidatus Liberibacter asiaticus

Diaphorina citri serves as the primary vector for Candidatus Liberibacter asiaticus (CLas), the bacterium associated with the severe Asian form of huanglongbing. CLas-positive D. citri are more fecund than their CLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response to CLas infection in D. citri. Knockdown of DcAKH and DcAKHR not only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity and CLas titer in ovaries. Combined in vivo and in vitro experiments showed that miR-34 suppresses DcAKHR expression by binding to its 3 untranslated region, whilst overexpression of miR-34 resulted in a decline of DcAKHR expression and CLas titer in ovaries and caused defects that mimicked DcAKHR knockdown phenotypes. Additionally, knockdown of DcAKH and DcAKHR significantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor, methoprene-tolerant (DcMet), and the transcription factor, Kruppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genes vitellogenin 1-like (DcVg-1-like), vitellogenin A1-like (DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result, CLas hijacks AKH/AKHR-miR-34-JH signaling to improve D. citri lipid metabolism and fecundity, while simultaneously increasing the replication of CLas, suggesting a mutualistic interaction between CLas and D. citri ovaries.

ecology↗