Biology subjects

Fang, J.

Publications and source records attributed to Fang, J..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Bio-macromolecular assembly machine for human limb lengthening

Growth plate (GP) is the critical cartilaginous structure for longitudinal bone growth. Herein, employing high-resolution analytical techniques, we explore the intricate mechanisms that govern the polarized mineralization patterns within GP. The GP-epiphysis interface displays a sharp transition in tissue modulus, acting as a "protective shell" for the underlying GP, whereas the GP-metaphysis interface exhibits a gradual modulus increase, enabling efficient load redistribution to metaphysis. The unique mechanical environments at these two interfaces contribute to polarized CaP mineralization patterns, which are regulated by a complex protein-based molecular machinery. The mineralization inhibitors SPP1 and AHSG enriched at the GP-epiphysis interface could act as a line of defence against mineralization. When these two proteins coexisted with the mineralization-promoting ENPP1 and ALPL at the GP-metaphysis interface, a sequential event of precise nucleation and programmable assembly of CaP minerals occur, forming "mineralization waves" to guide bone elongation. By replicating such specific macromolecular environment at GP-metaphysis interface, a hypertable amorphous calcium phosphate (ACP) phase is well-retained in vitro, demonstrating the possibility for precise and gentle control of ACP-hydroxyapatite (HAp) transformation under physiological conditions. Our study defines a novel concept of "mineralization waves" that govern the velocity and amplitude of GP-guided mineralization process.

bioengineering↗

bioRxiv2024

Centrocortin potentiates co-translational localization of its mRNA to the centrosome via dynein

Centrosomes rely upon proteins within the pericentriolar material to nucleate and organize microtubules. Several mRNAs also reside at centrosomes, although less is known about how and why they accumulate there. We previously showed that local Centrocortin (Cen) mRNA supports centrosome separation, microtubule organization, and viability in Drosophila embryos. Here, using Cen mRNA as a model, we examine mechanisms of centrosomal mRNA localization. We find that while the Cen N-terminus is sufficient for protein enrichment at centrosomes, multiple domains cooperate to concentrate Cen mRNA at this location. We further identify an N-terminal motif within Cen that is conserved among dynein cargo adaptor proteins and test its contribution to RNA localization. Our results support a model whereby Cen protein enables the accumulation of its own mRNA to centrosomes through a mechanism requiring active translation, microtubules, and the dynein motor complex. Taken together, our data uncover the basis of translation-dependent localization of a centrosomal RNA required for mitotic integrity. SummaryEnrichment of Centrocortin (Cen) mRNA at centrosomes is required for mitotic fidelity. This study describes a mechanism underlying co-translational Cen mRNA targeting involving microtubules, the dynein motor, and a highly conserved dynein binding motif within the Cen coding sequence.

cell biology↗

bioRxiv2024

A Tough Biointerface in Human Knee Empowered by Dynamic Phase-transforming Minerals in Collagenous Matrix

Joining heterogeneous materials in engineered structures remains a daunting challenge because of stress concentration, often resulting in unexpected failures1,2. Studying the structures in organisms that evolved for centuries provides valuable insights that can be instrumental in addressing this mechanical challenge3-5. The human meniscus root-bone interface is a remarkable example known for its exceptional fatigue resistance, toughness and interfacial adhesion properties throughout its lifespan6-8. We studied the multiscale graded mineralization structure designs within the 30-micron soft-hard interface at the root-bone junction and examined its toughening mechanisms. This graded interface with interdigitated structures and exponential modulus increase exhibits a phase transition from amorphous calcium phosphate (ACP) to gradually matured hydroxyapatite (HAP) crystals, mediated by location-specific distributed biomolecules. In coordination with collagen fibril deformation and reorientation, ACP particles debond with collagen and slide to new positions which enable frictional energy dissipation, and HAP particles arrest cracks. The mineral in transforming phases work synergistically to provide interfacial toughening. The presented biointerface model exemplifies human musculoskeletal systems adaptations to mechanical requirements, offering a blueprint for developing tough interfaces in broad applications.

bioengineering↗

bioRxiv2024

Substrate specificity and protein stability drive the divergence of plant-specific DNA methyltransferases

DNA methylation is an important epigenetic mechanism essential for transposon silencing and genome integrity. Across evolution, the substrates of DNA methylation have diversified between kingdoms to account for genome complexity. In plants, Chromomethylase3 (CMT3) and CMT2 are the major methyltransferases mediating CHG and CHH methylation, respectively. However, how these two enzymes diverge on substrate specificities during evolution remains unknown. Here, we reveal that CMT2 originates from a duplication of the evolutionarily more ancient CMT3 in flowering plants. Lacking a key arginine residue recognizing CHG in CMT2 impairs its CHG methylation activity in most flowering plants. An engineered V1200R mutation empowers CMT2 to restore both CHG and CHH methylation in Arabidopsis cmt2cmt3 mutant, testifying a loss-of-function effect for CMT2 after [~]200 million years of evolution. Interestingly, CMT2 has evolved a long and unstructured N-terminus critical for balancing protein stability, especially under heat stress. Furthermore, CMT2 N-terminus is plastic and can be tolerant to various natural mutations. Together, this study reveals the mechanism of chromomethylase divergence for context-specific DNA methylation in plants and sheds important lights on DNA methylation evolution and function.

plant biology↗

bioRxiv2024

A multi-gene predictive model for the radiation sensitivity of nasopharyngeal carcinoma based on machine learning

BackgroundRadiotherapy resistance is a major obstacle to the long-term survival of nasopharyngeal cancer patients, as it is a primary cause of recurrence and metastasis. Identifying radiotherapy-associated biomarkers can help improve the survival prognosis of nasopharyngeal cancer patients. Consequently, discovering biomarkers associated with radiosensitization is crucial. MethodsWe evaluated 113 combinations of machine learning algorithms and ultimately selected 48 to construct a radiotherapy sensitivity score (NPC-RSS) that can predict radiosensitivity in nasopharyngeal cancer patients. Furthermore, we analyzed the relationship between NPC-RSS and the expression of genes associated with immune and radiotherapy sensitivity profiles. We employed GSEA and ssGSEA to investigate the connection between NPC-RSS and signaling pathways. ResultsWe selected the combined model glmBoost+NaiveBayes, which had the best AUC among 48 models, for our subsequent study. The NPC-RSS, built based on the 18 genes included in this model, can predict the results of the public dataset and the in-house dataset of Zhujiang Hospital, Southern Medical University, with considerable efficiency. The key genes of NPC-RSS are closely associated with immune characteristics, including chemokine and chemokine receptor families, and histocompatibility complex (MHC), and show more active immune processes. Meanwhile, these key genes were significantly associated with the expression of radiosensitization-related genes. Furthermore, GSVA and GSEA analyses demonstrated that different expression levels of key NPC-RSS genes influenced signaling pathways, such as the Wnt/{beta}-catenin signaling pathway, JAK-STAT signaling pathway,NF-kappa B signaling pathway and T cell receptor signaling pathway, which are associated with immunity and disease progression. The consistency of the expression of key genes SMARCA2 and CD9 with NPC-RSS was validated in in-house cell lines. The radiosensitive group, classified according to NPC-RSS, exhibited a more enriched and activated state of immune infiltration compared to the radioresistant group. Moreover, in single-cell samples, NPC-RSS was higher in the radiotherapy-sensitive group, with immune cells playing a predominant role. ConclusionsIn this study, we used machine learning to construct a predictive score, called NPC-RSS, associated with radiosensitivity in nasopharyngeal carcinoma patients; moreover, NPC-RSS is strongly associated with immune characteristics, expression of radiosensitivity-related genes, and signaling pathways related to disease progression. We hope that the NPC-RCC will enable more precise selection of the NPC population of potential beneficiaries of radiation therapy.

bioinformatics↗

bioRxiv2024

Universal protection of allogeneic cell therapies from natural killer cells via CD300a agonism

Immunogenicity limits the persistence of off-the-shelf, allogeneic cell therapies and transplants. While ablation of human leukocyte antigen (HLA) removes most T cell and humoral alloreactivity, no solution has enabled universal protection against the resulting natural killer (NK) cell response. Here, we engineered Trans Antigen Signaling Receptors (TASR) as a new class of NK inhibitory ligands and discovered CD300a, a previously inaccessible receptor, as a functional target. CD300a TASR outperformed leading alternative strategies in focused screens, including CD47 and HLA-E, and was solely capable of universally protecting allogeneic T cells against a large human cohort (45/45 donors), spanning diverse demographics and NK cell phenotypes. A model allogeneic T cell therapy co-expressing an anti-CD19 Chimeric Antigen Receptor (CAR) and CD300a TASR, produced using multiplexed non-viral integration, exhibited enhanced B cell killing potency under allogeneic immune pressure. CD300 TASR represents a universal solution to NK alloreactivity, broadening the population that could be effectively treated by next-generation allogeneic cell therapies. CategoryImmunobiology and Immunotherapy Key PointsO_LIAn engineered CD300a agonist ligand (CD300a TASR) universally protects HLA-deficient allogeneic T cells from NK-mediated rejection. C_LIO_LICD300a TASR is more protective in CMV seropositive hosts than HLA-E ligand and enhances CAR-T efficacy under allogeneic immune pressure. C_LI

immunology↗

bioRxiv2024

Imaging the large-scale and cellular cortical response to focal traumatic brain injury in mouse neocortex

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behavior are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that traveled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two-photon calcium imaging in primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced traveling wave. A depression of calcium signals followed the wave, during which we observed atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioral measures. Neural and behavioral changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

neuroscience↗

bioRxiv2024

Chromosomal-level genome assembly and single-nucleotide polymorphism sites of black-faced spoonbill Platalea minor

Platalea minor, the black-faced spoonbill (Threskiornithidae) is a wading bird that is confined to coastal areas in East Asia. Due to habitat destruction, it has been classified by The International Union for Conservation of Nature (IUCN) as globally endangered species. Nevertheless, the lack of its genomic resources hinders our understanding of their biology, diversity, as well as carrying out conservation measures based on genetic information or markers. Here, we report the first chromosomal-level genome assembly of P. minor using a combination of PacBio SMRT and Omni-C scaffolding technologies. The assembled genome (1.24 Gb) contains 95.33% of the sequences anchored to 31 pseudomolecules. The genome assembly also has high sequence continuity with scaffold length N50 = 53 Mb. A total of 18,780 protein-coding genes were predicted, and high BUSCO score completeness (93.7% of BUSCO metazoa_odb10 genes) was also revealed. A total of 6,155,417 bi-allelic SNPs were also revealed from 13 P. minor individuals, accounting for [~]5% of the genome. The resource generated in this study offers the new opportunity for studying the black-faced spoonbill, as well as carrying out conservation measures of this ecologically important spoonbill species.

genomics↗

bioRxiv2024

An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking

BackgroundIdentifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. MethodsSurface EEG signals and real-time Ca2+ activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. ResultsAn EEG waveform derivative - a modified theta-to-delta ratio (EEG Ratio) - accurately tracks real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions. ConclusionsThe identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.

neuroscience↗

bioRxiv2024

RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticity

The cellular plasticity of neuroblastoma is defined by a mixture of two major cell states, adrenergic (ADRN) and mesenchymal (MES), which may contribute to therapy resistance. However, how neuroblastoma cells switch cellular states during therapy remains largely unknown and how to eradicate neuroblastoma regardless of their cell states is a clinical challenge. To better understand the lineage switch of neuroblastoma in chemoresistance, we comprehensively defined the transcriptomic and epigenetic map of ADRN and MES types of neuroblastomas using human and murine models treated with indisulam, a selective RBM39 degrader. We showed that cancer cells not only undergo a bidirectional switch between ADRN and MES states, but also acquire additional cellular states, reminiscent of the developmental pliancy of neural crest cells. The lineage alterations are coupled with epigenetic reprogramming and dependency switch of lineage-specific transcription factors, epigenetic modifiers and targetable kinases. Through targeting RNA splicing, indisulam induces an inflammatory tumor microenvironment and enhances anticancer activity of natural killer cells. The combination of indisulam with anti-GD2 immunotherapy results in a durable, complete response in high-risk transgenic neuroblastoma models, providing an innovative, rational therapeutic approach to eradicate tumor cells regardless of their potential to switch cell states.

cancer biology↗

bioRxiv2024

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma

The MYC proto-oncogenes (c-MYC, MYCN, MYCL) are among the most deregulated oncogenic drivers in human malignancies including high-risk neuroblastoma, 50% of which are MYCN-amplified. Genetically engineered mouse models (GEMMs) based on the MYCN transgene have greatly expanded the understanding of neuroblastoma biology and are powerful tools for testing new therapies. However, a lack of c-MYC-driven GEMMs has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and therapy development given that c-MYC is also an important driver of many high-risk neuroblastomas. In this study, we report two transgenic murine neuroendocrine models driven by conditional c-MYC induction in tyrosine hydroxylase (Th) and dopamine {beta}-hydroxylase (Dbh)-expressing cells. c-MYC induction in Th-expressing cells leads to a preponderance of Pdx1+ somatostatinomas, a type of pancreatic neuroendocrine tumor (PNET), resembling human somatostatinoma with highly expressed gene signatures of {delta} cells and potassium channels. In contrast, c-MYC induction in Dbh-expressing cells leads to onset of neuroblastomas, showing a better transforming capacity than MYCN in a comparable C57BL/6 genetic background. The c-MYC murine neuroblastoma tumors recapitulate the pathologic and genetic features of human neuroblastoma, express GD2, and respond to anti-GD2 immunotherapy. This model also responds to DFMO, an FDA-approved inhibitor targeting ODC1, which is a known MYC transcriptional target. Thus, establishing c-MYC-overexpressing GEMMs resulted in different but related tumor types depending on the targeted cell and provide useful tools for testing immunotherapies and targeted therapies for these diseases.

cancer biology↗

bioRxiv2024

A Microphysiological HHT-on-a-Chip Platform Recapitulates Patient Vascular Lesions

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations focally develop in multiple organs. These can be small (telangiectasias) or large (arteriovenous malformations, AVMs) and may rupture leading to frequent, uncontrolled bleeding. There are few treatment options and no cure for HHT. Most HHT patients are heterozygous for loss-of-function mutations for Endoglin (ENG) or Alk1 (ACVRL1), however, why loss of these genes manifests as vascular malformations remains poorly understood. To complement ongoing work in animal models, we have developed a microphysiological system model of HHT. Based on our existing vessel-on-a-chip (VMO) platform, our fully human cell-based HHT-VMO recapitulates HHT patient vascular lesions. Using inducible ACVRL1 (Alk1)-knockdown, we control timing and extent of endogenous Alk1 expression in primary human endothelial cells (EC) in the HHT-VMO. HHT-VMO vascular lesions develop over several days, and are dependent upon timing of Alk1 knockdown. Interestingly, in chimera experiments AVM-like lesions can be comprised of both Alk1-intact and Alk1-deficient EC, suggesting possible cell non-autonomous effects. Single cell RNA sequencing data are consistent with microvessel pruning/regression as contributing to AVM formation, while loss of PDGFB expression implicates mural cell recruitment. Finally, lesion formation is blocked by the VEGFR inhibitor pazopanib, mirroring the positive effects of this drug in patients. In summary, we have developed a novel HHT-on-a-chip model that faithfully reproduces HHT patient lesions and that is sensitive to a treatment effective in patients. The VMO-HHT can be used to better understand HHT disease biology and identify potential new HHT drugs. SignificanceThis manuscript describes development of an organ-on-a-chip model of Hereditary Hemorrhagic Telangiectasia (HHT), a rare genetic disease involving development of vascular malformations. Our VMO-HHT model produces vascular malformations similar to those seen in human HHT patients, including small (telangiectasias) and large (arteriovenous malformations) lesions. We show that VMO-HHT lesions are sensitive to a drug, pazopanib, that appears to be effective in HHT human patients. We further use the VMO-HHT platform to demonstrate that there is a critical window during vessel formation in which the HHT gene, Alk1, is required to prevent vascular malformation. Lastly, we show that lesions in the VMO-HHT model are comprised of both Alk1-deficient and Alk1-intact endothelial cells.

cell biology↗

bioRxiv2024

Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma1,2. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance3. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD+) catabolism, is highly expressed in exhausted CD8+ T cells in melanoma and is associated with ICB resistance. Tumour-derived CD38hiCD8+ T cells are dysfunctional, characterised by impaired proliferative capacity, effector function, and dysregulated mitochondrial bioenergetics. Genetic and pharmacological blockade of CD38 in murine and patient-derived organotypic tumour models (MDOTS/PDOTS) enhanced tumour immunity and overcame ICB resistance. Mechanistically, disrupting CD38 activity in T cells restored cellular NAD+ pools, improved mitochondrial function, increased proliferation, augmented effector function, and restored ICB sensitivity. Taken together, these data demonstrate a role for the CD38-NAD+ axis in promoting T cell exhaustion and ICB resistance, and establish the efficacy of CD38 directed therapeutic strategies to overcome ICB resistance using clinically relevant, patient-derived 3D tumour models.

cancer biology↗

bioRxiv2024

Genome assembly of the edible jelly fungus Dacryopinax spathularia (Dacrymycetaceae)

The edible jelly fungus Dacryopinax spathularia (Dacrymycetaceae) is wood-decaying and can be commonly found worldwide. It has also been used in food additives given its ability to synthesize long-chain glycolipids. In this study, we present the genome assembly of D. spathularia using a combination of PacBio HiFi reads and Omni-C data. The genome size of D. spathularia is 29.2 Mb and in high sequence contiguity and completeness, including scaffold N50 of 1.925 Mb and 92.0% BUSCO score, respectively. A total of 11,510 protein-coding genes, and 474.7 kb repeats accounting for 1.62% of the genome, were also predicted. The D. spathularia genome assembly generated in this study provides a valuable resource for understanding their ecology such as wood decaying capability, evolutionary relationships with other fungus, as well as their unique biology and applications in the food industry.

genomics↗

bioRxiv2024

Chromosomal-level genome assembly of the long-spined sea urchin Diadema setosum (Leske, 1778)

The long-spined sea urchin Diadema setosum is an algal and coral feeder widely distributed in the Indo-Pacific and can cause severe bioerosion on the reef community. Nevertheless, the lack of genomic information has hindered the study its ecology and evolution. Here, we report the chromosomal-level genome (885.8 Mb) of the long-spined sea urchin D. setosum using a combination of PacBio long-read sequencing and Omni-C scaffolding technology. The assembled genome contained scaffold N50 length of 38.3 Mb, 98.1 % of BUSCO (Geno, metazoa_odb10) genes, and with 98.6% of the sequences anchored to 22 pseudo-molecules/chromosomes. A total of 27,478 genes including 23,030 protein-coding genes were annotated. The high-quality genome of D. setosum presented here provides a significant resource for further understanding on the ecological and evolutionary studies of this coral reef associated sea urchin.

genomics↗

bioRxiv2024

Genome assembly of the rare and endangered Grantham's camellia, Camellia granthamiana

The Granthams camellia (Camellia granthamiana Sealy) is a rare and endangered tea species that is endemic to southern China, and was first discovered in Hong Kong in 1955. Despite its high conservation value, genomic resources of C. granthamiana remain limited. Here, we present a chromosome-scale draft genome of the tetraploid C. granthamiana (2n = 4x = 60) using a combination of PacBio long read sequencing and Omni-C data. The assembled genome size is [~]2.4 Gb with most sequences anchored to 15 pseudochromosomes that resemble a monoploid genome. The genome is of high contiguity, with a scaffold N50 of 139.7 Mb, and high completeness with a 97.8% BUSCO score. Gene model prediction resulted in a total 76,992 protein-coding genes with a BUSCO score of 85.9%. 1.65 Gb of repeat content was annotated, which accounts for 68.48% of the genome. The Granthams camellia genome assembly provides a valuable resource for future investigations on its biology, ecology, phylogenomic relationships with other Camellia species, as well as set up a foundation for further conservation measures.

plant biology↗

bioRxiv2024

Chromosome-level genome assembly of the common chiton, Liolophura japonica (Lischke, 1873)

Chitons (Polyplacophora) are marine molluscs that can be found worldwide from cold waters to the tropics, and play important ecological roles in the environment. Nevertheless, there remains only two chiton genomes sequenced to date. The chiton Liolophura japonica (Lischke, 1873) is one of the most abundant polyplacophorans found throughout East Asia. Our PacBio HiFi reads and Omni-C sequencing data resulted in a high-quality near chromosome-level genome assembly of [~]609 Mb with a scaffold N50 length of 37.34 Mb (96.1% BUSCO). A total of 28,233 genes were predicted, including 28,010 protein-coding genes. The repeat content (27.89%) was similar to the other Chitonidae species and approximately three times lower than in the genome of the Hanleyidae chiton. The genomic resources provided in this work will help to expand our understanding of the evolution of molluscs and the ecological adaptation of chitons.

genomics↗

bioRxiv2024

Genome assembly of the milky mangrove Excoecaria agallocha

The milky mangrove Excoecaria agallocha is a latex-secreting mangrove that are distributed in tropical and subtropical regions. While its poisonous latex is regarded as a potential source of phytochemicals for biomedical applications, the genomic resources of E. agallocha remains limited. Here, we present a chromosomal level genome of E. agallocha, assembled from the combination of PacBio long-read sequencing and Omni-C data. The resulting assembly size is 1,332.45 Mb and has high contiguity and completeness with a scaffold N50 of 58.9 Mb and a BUSCO score of 98.4 %. 73,740 protein-coding genes were also predicted. The milky mangrove genome provides a useful resource for further understanding the biosynthesis of phytochemical compounds in E. agallocha.

genomics↗