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Gong, Z.

Publications and source records attributed to Gong, Z..

At least 73 records · Page 4Linked to original sources

The minor spliceosome offers a therapeutically viable target for the treatment of a broad spectrum of cancers

Minor splicing is a second splicing system required for the correct expression of [~]700 human minor intron-containing genes (MIGs). Many MIGs are expressed in vigorously proliferating cells and are frequently dysregulated in cancer including BRAF, ERK, JNK and p38. Minor splicing is carried out by the minor spliceosome which comprises several unique components, including a 65kDa protein encoded by RNPC3. We show that Rnpc3 heterozygosity reduces tumour burden in a broad spectrum of in vivo cancer settings, without harming normal tissues. Using the collective power of zebrafish, mouse and human cancer models, we reveal a sequence of events connecting Rnpc3 deficiency and impaired splicing of MIGs to DNA damage and activation of a Tp53-dependent transcriptional program that restricts tumour burden by inducing cell cycle arrest and apoptosis. Interrogation of human liver and lung cancer transcriptomes curated in TCGA revealed that the expression of many of the genes encoding protein components of the minor spliceosome is upregulated in these cancers. This is accompanied by upregulation of the expression of MIGs that are enriched in cell cycle and DNA damage pathways. These findings suggest that cancer cells can invoke mechanisms to increase the efficiency of minor splicing to support their high proliferation rates. Finally, Kaplan Meier survival analysis shows that highly expressed MIGs are frequently associated with poor patient survival. Taken together, these results indicate that the minor spliceosome offers a therapeutically viable target for the treatment of a broad spectrum of cancers.

cancer biology↗

Representation of Drosophila larval behaviors by muscle activity patterns

How muscle actions are coordinated to realize animal movement is a fundamental question in behavioral study. To obtain the overall muscular activity patterns accompanying behaviors at high spatiotemporal resolution is technically difficult. In this work, we used light sheet microscopy to simultaneously image and analyze the activity, length and orientation of Drosophila larval muscles across body segments at single muscle resolution in nearly free behaviors. For typical behavioral modes such as peristalsis, head cast and turning, larval muscles showed behavioral mode specific activity patterns. Unexpectedly, reorientation of larval head involves muscle tone in the apparently motionless posterior segments. With a STGCN(spatial temporal graph convolution neural network)-Generator model, sequence of larval behavioral poses outlined by morphological patterns of muscles could be accurately predicted based on the time series of ventral but not dorsal muscle activities, and vice versa. Laser ablation of ventral but not dorsal muscles interrupted peristaltic wave and undermined head cast in both frequency and amplitude. Our results provide a simplified muscle activity representation of soft body motion that can be used for probing the key components of animal motor control.

neuroscience↗

Chemo-mechanical Diffusion Waves Orchestrate Collective Dynamics of Immune Cell Podosomes

Immune cells, such as macrophages and dendritic cells, can utilize podosomes, actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. In these cells, individual podosomes exhibit periodic protrusion and retraction cycles (vertical oscillations) to probe their microenvironment, while multiple podosomes arranged in clusters demonstrate coordinated wave-like spatiotemporal dynamics. However, the mechanisms governing both the individual vertical oscillations and the coordinated oscillation waves in clusters remain unclear. By integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for both the oscillatory growth of individual podosomes and wave-like dynamics in clusters. Our model reveals that podosomes show oscillatory growth when the actin polymerization-associated protrusion and the signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers within the cluster drives mesoscale coordination of individual podosome oscillations in an apparent wave-like fashion. Our model predicts the influence of different pharmacological treatments targeting myosin activity, actin polymerization, and mechanosensitive pathways, as well as the impact of the microenvironment stiffness on the wavelengths, frequencies, and speeds of the chemo-mechanical waves. Overall, our integrated theoretical and experimental approach reveals how collective wave dynamics arise due to the coupling between chemo-mechanical signaling and actin diffusion, shedding light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.

biophysics↗

Whole transcriptome sequencing reveals drought resistance-related genes in upland cotton

China, especially the Xinjiang cotton area, is facing severe agricultural water shortages, which seriously restrain the development of the cotton industry. Discovering cotton drought resistance genes and cultivating high-quality and drought-resistant cotton materials through molecular breeding methods are of great significance to the development of the cotton industry. In this study, the drought-resistant cotton material Xinluzhong NO.82 and the drought-sensitive cotton material Kexin NO.1 were used to identify a batch of drought-resistant candidate genes through whole transcriptome sequencing. The main research results obtained were as follows: the ceRNA (competing endogenous RNAs) network was constructed using full transcriptional sequencing to screen the core genes in the core pathway; two drought-related candidate genes were obtained. Gohir.A11G156000 was upregulated at 0 h vs 12 h and downregulated at 12 h vs 24 h. Gohir.A07G220600 was downregulated at 0 h vs 12 h and upregulated at 12 h vs 24 h. The results for drought-resistant materials and drought-sensitive materials were similar. Gohir.A11G156000, encoding GABA-T, which is homologous to POP2 in Arabidopsis thaliana, affects the drought resistance of plants by regulating the GABA content. Gohir.A07G220600 encodes L-aspartate oxidase, which is homologous to AO in Arabidopsis thaliana, and is involved in the early steps of NAD biosynthesis and in plant antioxidant reactions. This study confirmed that the use of gene expression regulatory networks can quickly screen reliable drought-resistance genes and can be used for subsequent gene function verification.

genomics↗

Nucleobase clustering contributes to the formation and hollowing of repeat-expansion RNA condensate

RNA molecules with repeat expansion sequences can phase separate into gel-like condensate, and this process may lead to neurodegenerative diseases. Here we report that in the presence of Mg2+ ion, RNA molecules containing 20xCAG repeats coacervate into filled droplets or hollowed condensate. Using hyperspectral stimulated Raman spectroscopy, we show that RNA coacervation is accompanied by the stacking and clustering of nucleobases, while forfeiting the canonical base-paired structure. At an increasing RNA/Mg2+ ratio, the RNA droplets first expand in sizes, and then shrink and adopt hollow vesicle-like structures. Significantly, for both large and vesicle-like droplets, the nucleobase-clustered structure is more prominent at the rim than at the center, accounting for the rigidification of RNA droplets. Thus, our finding has broad implications for the general aging processes of RNA-containing membrane-less organelles.

biochemistry↗

Autophagy-dependent TOR reactivation drives fungal growth in living host rice cells

Eukaryotic filamentous plant pathogens with biotrophic growth stages like the devastating hemibiotrophic rice blast fungus Magnaporthe oryzae grow for extended periods in living host plant cells without eliciting defense responses. M. oryzae elaborates invasive hyphae (IH) that grow in and between living rice cells while separated from host cytoplasm by plant-derived membrane interfaces. However, although critical to the plant infection process, the molecular mechanisms and metabolic strategies underpinning this intracellular growth phase are poorly understood. Eukaryotic cell growth depends on activated target-of-rapamycin (TOR) kinase signaling, which inhibits autophagy. Here, using live-cell imaging coupled with plate growth tests and RNAseq, proteomic, quantitative phosphoproteomics and metabolic approaches, we show how cycles of autophagy in IH modulate TOR reactivation via -ketoglutarate to sustain biotrophic growth and maintain biotrophic interfacial membrane integrity in host rice cells. Deleting the M. oryzae serine-threonine protein kinase Rim15-encoding gene attenuated biotrophic growth, disrupted interfacial membrane integrity and abolished the in planta autophagic cycling we observe here for the first time in wild type.{Delta} rim15 was also impaired for glutaminolysis and depleted for -ketoglutarate. -ketoglutarate treatment of{Delta} rim15-infected leaf sheaths remediated{Delta} rim15 biotrophic growth. In WT, -ketoglutarate treatment suppressed autophagy. -ketoglutarate signaling is amino acid prototrophy- and GS-GOGAT cycle-dependent. We conclude that, following initial IH elaboration, cycles of Rim15- dependent autophagic flux liberate -ketoglutarate - via the GS-GOGAT cycle - as an amino acid-sufficiency signal to trigger TOR reactivation and promote fungal biotrophic growth in nutrient-restricted host rice cells.

plant biology↗

The genome of an apodid holothuroid (Chiridota heheva) provides insights into its adaptation to deep-sea reducing environment

Cold seeps and hydrothermal vents are deep-sea reducing environments that are characterized by a lack of oxygen, photosynthesis-derived nutrients and a high concentration of reducing chemicals. Apodida is an order of deep-sea echinoderms lacking tube feet and complex respiratory trees, which are commonly found in holothurians. Chiridota heheva Pawson & Vance, 2004 (Apodida: Chiridotidae) is one of the few echinoderms that resides in deep-sea reducing environments. Unlike most cold seep and hydrothermal vent-dwelling animals, C. heheva does not survive by maintaining an epi- or endosymbiotic relationship with chemosynthetic microorganisms. The species acquires nutrients by extracting organic components from sediment detritus and suspended material. Here, we report a high-quality genome of C. heheva as a genomic reference for echinoderm adaptation to reducing environments. Chiridota heheva likely colonized its current habitats in the early Miocene. The expansion of the aerolysin-like protein family in C. heheva compared with other echinoderms might be involved in the disintegration of microbes during digestion, which in turn facilitates the species adaptation to cold seep environments. Moreover, several hypoxia-related genes were subject to positive selection in the genome of C. heheva, which contributes to their adaptation to hypoxic environments.

genomics↗

Genome-wide association analysis of cotton salt stress response-related sites

Soil salinization is the main abiotic stress factor affecting agricultural production worldwide, and salt stress has a significant impact on plant growth and development. Cotton is one of the most salt-tolerant crops. Its salt tolerance varies greatly depending on the variety, growth stage, organs, and soil salt types. Therefore, the selection and utilization of excellent salt-tolerant germplasm resources and the excavation of excellent salt-tolerant salt and salt resistance genes play important roles in improving cotton production in saline-alkali soils. In this study, we analysed the population structure and genetic diversity of 144 elite Gossypium hirsutum cultivar accessions collected from around the world, and especially from China. Illumina Cotton SNP 70K was used to obtain genome-wide single-nucleotide polymorphism (SNP) data for 149 experimental materials, and 18,432 highly consistent SNP loci were obtained by filtering. PCA (principal component analysis) indicated that 149 upland cotton materials could be divided into 2 subgroups, including subgroup 1 with 78 materials and subgroup 2 with 71 materials. Using the obtained SNP and other marker genotype test results, under salt stress, the salt tolerance traits 3d_Germination_potential, 3d_Bud_length_drop_rate, 7d_Germination_rate, 7d_Bud_length_drop_rate, 7d_Germination_weight, 3d_Bud_length, 7d_Bud_length, relative_germination_potential, Relative_germination_rate, 7d_Bud_weight_drop_rate, Salt tolerance index 3d_Germination_potential_index, 3d_Bud_length_index, 7d_Bud_length_index, 7d_Bud_weight_index, and 7d_Germination_rate_index were evaluated by genome association analysis. A total of 27 SNP markers closely related to salt tolerance traits and 15 SNP markers closely related to salt tolerance index were detected. At the SNP locus associated with the traits of the bud length decline rate at 7 days, alleles Gh_A01G0034 and Gh_D01G0028 related to plant salt tolerance were detected, and they are related to intracellular transport, membrane microtubule formation and actin network. This study provides a theoretical basis for the selection and breeding of salt-tolerant upland cotton varieties.

genomics↗

Elys deficiency constrains Kras-driven tumour burden by amplifying oncogenic stress

The nucleoporin ELYS, encoded by AHCTF1, is a large multifunctional protein with essential roles in nuclear pore assembly and mitosis. Using a zebrafish model of hepatocellular carcinoma, in which the expression of an inducible mutant kras transgene (krasG12V) drives hepatocyte-specific hyperplasia and liver enlargement, we show that reducing ahctf1 gene dosage by 50% markedly shrinks tumour burden, while non-hyperplastic tissues are unaffected. We demonstrate that ahctf1 heterozygosity impairs nuclear pore formation, mitotic spindle assembly and chromosome segregation, leading to DNA damage and activation of TP53-dependent and independent mechanisms of cell death and cell cycle arrest. This selective vulnerability of cancer cells to mild disruption of Elys function uncovers a novel synthetic lethal interaction between ahctf1 and kras mutations that could be exploited therapeutically. Heterozygous expression of both ahctf1 and ranbp2, or treatment of heterozygous ahctf1 larvae with the nucleocytoplasmic transport inhibitor, Selinexor, completely blocked krasG12V-driven hepatocyte hyperplasia, revealing promising avenues for combinatorial treatments.

cancer biology↗

A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice

The emergence of Zika virus (ZIKV) infection, which is an unexpectedly associated with congenital defects, has prompted the development of safe and effective vaccines. The gram-positive enhancer matrix-protein anchor (GEM-PA) display system has emerged as a versatile and highly effective platform for delivering target proteins for vaccines. In this article, we developed a bacterium-like particle vaccine ZI-{Delta}-PA-GEM based on the GEM-PA system. The fusion protein ZI-{Delta}-PA, which contains the prM-E-{Delta} protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3, was expressed. The fusion protein was successfully displayed on the GEM surface, forming ZI-{Delta}-PA-GEM. Moreover, when BALB/c mice were immunized intramuscularly with ZI-{Delta}-PA-GEM combined with 201 VG and poly(I:C) adjuvants, durable ZIKV-specific IgG and protective neutralizing antibody responses were induced. Potent B cell/DC activation was also be stimulated early after immunization. Remarkably, splenocyte proliferation, the secretion of multiple cytokines, T/B cell activation and central memory T cell responses were elicited. These data indicate that ZI-{Delta}-PA-GEM is a promising bacterium-like particle vaccine candidate for ZIKV. Author summaryBecause Zika virus (ZIKV) infection is considered as an example of "disease X", the development of a safe and effective ZIKV vaccine is essential. The gram-positive enhancer matrix-protein anchor (GEM-PA) display system has been used in many vaccine studies due to its advantages. In this study, prM-E-{bigtriangleup} protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3 was fusion expressed, termed ZI-{bigtriangleup}-PA. Then the fusion protein ZI-{bigtriangleup}-PA could be displayed on the surface of GEM, forming ZI-{bigtriangleup}-PA-GEM. The author evaluated the immunogenicity of ZI-{bigtriangleup}-PA-GEM with the 201 VG and poly(I:C) adjuvants. The study demonstrates that ZI-{bigtriangleup}-PA-GEM induced mice to produce neutralizing antibody and specific cellular immune responses. The author believe that the bacterium-like particle vaccine ZI-{bigtriangleup}-PA-GEM has the potential to be used as the ZIKV vaccine.

microbiology↗

Preferential interactions of a crowder protein with the specific binding site of a native protein complex

The crowded cellular environments provide ample opportunities for proteins to interact with bystander macromolecules, yet direct evidence, let alone residue-specific information, for such nonspecific binding is rare. Here, by combining NMR spectroscopy and atomistic modeling, we investigated how crowders influence the association equilibrium and kinetics of two protein partners, EIN and HPr. Ficoll-70 increases the EIN-HPr binding affinity whereas bovine serum albumin (BSA) decreases the affinity. The opposite effects of the two crowders are quantitatively explained by atomistic modeling, which shows that the stabilizing effect of Ficoll-70 arises from volume exclusion favoring the bound state. In contrast, the destabilizing effect of BSA arises from preferential soft interactions with the free state; notably, BSA has favorable electrostatic interactions with positively charged HPr residues within the EIN-binding site. Some of the residues from this site indeed experience significant chemical shift perturbation when titrated with BSA, while the relaxation rates of HPr backbone amides exhibit overall elevation. Furthermore, relaxation dispersion data indicate that Ficoll-70 and BSA both slow down the EIN-HPr association rate, but change the dissociate rate in opposite directions. The observations on kinetics are accounted for by two effects of the crowders: increasing the solution microviscosity and reshaping the EIN-HPr interaction energy surface. The kind of preferential interactions between BSA and HPr that leads to competition with EIN should be prevalent in cellular environments. Our NMR results and atomistic modeling provide benchmarks, at both qualitative and quantitative levels, for the effects of crowded cellular environments on protein-protein specific interactions. Significance StatementAlthough nonspecific binding of crowder macromolecules with functional proteins is likely prevalent in vivo, direct evidence is rare. Here we present NMR characterizations showing that bovine serum albumin preferentially interacts with a specific binding site on HPr, leading to competition with the latters partner EIN. The preferential interactions result in destabilization of the EIN-HPr native complex and speedup of its dissociation, contrary to expectations from excluded-volume and viscosity effects. Atomistic modeling of macromolecular crowding rationalizes the experimental observations, and provides qualitative and quantitative insight into the influences of the crowded cellular environment on protein-protein specific interactions. Our work also has implications for evolution, regarding how nonspecific binding can be either minimized or exploited for gaining new functions.

biophysics↗

Development of a compact alkynyl-enrichable crosslinker for in-depth in-vivo crosslinking analysis

Chemical crosslinking coupled with mass spectrometry (CXMS) has emerged as a powerfl technique to capture the dynamic information of protein complexes with high sensitivity, throughput and sample universality. To advance the study of in-vivo protein structures and protein-protein interactions on the large scale, a new alkynyl-enrichable crosslinker was developed with high efficiency of membrane penetration, reactivity and enrichment. The crosslinker was successfully used for in-vivo crosslinking of intact human cells, reslting in 6820 non-redundant crosslinks identified at a false discovery rate (FDR) of 1% using pLink 2.0, which 4898 (71.8%) of the cross-links were assigned as intraprotein and 1922 (28.2%) were interprotein links. To our knowledge, this is also the first time to realize the in-vivo crosslinking with a non-cleavable crosslinker for homo species cells.

biochemistry↗

Analysis of the Genetic Structure and Diversity of Upland Cotton Groups in Different Planting Areas Based on SNP Markers

Genetic diversity, kinship and population genetic structure analyses of Gossypium hirsutum germplasm can provide a better understanding of the origin and evolution of G. hirsutum biodiversity. In this study, 1313331 SNP molecular markers were used to construct a phylogenetic tree of each sample using MEGAX, to perform population structure analysis by ADMIXTURE software and principal component analysis (PCA) by EIGENSOFT software, and to estimate relatedness using SPAGeDi. ADMIXTURE software divided the experimental cotton population into 16 subgroups, and the Gossypium hirsutum samples could be roughly clustered according to source place, but there were some overlapping characteristics among samples. The experimental cotton population was divided into six groups according to source to calculate the genetic diversity index (H), and the obtained value (0.306) was close to that for germplasm collected by others in China. Cluster 4 had a relatively high genetic diversity level (0.390). The degrees of genetic differentiation within the experimental cotton population groups were low (the population differentiation indexes ranged from 0.02368 to 0.10664). The genetic distance among cotton accessions varied from 0.000332651 to 0.562664014, with an average of 0.25240429. The results of this study may provide a basis for mining elite alleles and using them for subsequent association analysis.

genomics↗

Deep-learning on-chip DSLM enabling video-rate volumetric imaging of neural activities in moving biological specimens

Volumetric imaging of dynamic signals in a large, moving, and light-scattering specimen is extremely challenging, owing to the requirement on high spatiotemporal resolution and difficulty in obtaining high-contrast signals. Here we report that through combing a microfluidic chip-enabled digital scanning light-sheet illumination strategy with deep-learning based image restoration, we can realize isotropic 3D imaging of crawling whole Drosophila larva on an ordinary inverted microscope at single-cell resolution and high volumetric imaging rate up to 20 Hz. Enabled with high performances even unmet by current standard light-sheet fluorescence microscopes, we intoto record the neural activities during the forward and backward crawling of 1st instar larva, and successfully correlate the calcium spiking of motor neurons with the locomotion patterns.

bioengineering↗

Verticillium dahliae effector VDAL protects MYB6 from degradation by interacting with PUB25/26 E3 ligases for enhancing Verticillium wilt resistance in Arabidopsis

Verticillium wilt is a severe plant disease that causes massive losses in multiple crops. Increasing the plant resistance to Verticillium wilt is a critical challenge worldwide. Here, we report that the hemibiotrophic Verticillium dahliae (V. dahliae)-secreted Asp f2-like protein VDAL causes leaf wilting when applied to cotton leaves in vitro, but enhances the resistance to V. dahliae when overexpressed in Arabidopsis or cotton without affecting the plant growth and development. VDAL protein interacts with Arabidopsis E3 ligases PUB25 and PUB26 (PUBs) and is ubiquitinated by PUBs in vitro. However, VDAL is not degraded by PUB25 or PUB26 in planta. Besides, the pub25 pub26 double mutant shows higher resistance to V. dahliae than the wild type. PUBs interact with the transcription factor MYB6 in a yeast two-hybrid screen. MYB6 promotes plant resistance to Verticillium wilt while PUBs ubiquitinate MYB6 and mediate its degradation. VDAL competes with MYB6 for binding to PUBs, and the role of VDAL in increasing Verticillium wilt resistance depends on MYB6. Taken together, these results suggest that plants evolute a strategy to utilize the invaded effector protein VDAL to resist the V. dahliae infection without causing a hypersensitive response (HR), Alternatively, in order to take nutrients from host cells, hemibiotrophic pathogens may use some effectors to keep plant cells alive during its infection in order to take nutrients from host cells. This study provides the molecular mechanism for plants increasing disease resistance when overexpressing some effector proteins without inducing HR, and may promote searching for more genes from pathogenic fungi or bacteria to engineer plant disease resistance. One-sentence summaryEctopically expressed VDAL in Arabidopsis alleviates the degradation of a positive disease response factor MYB6 through its interaction with PUB25/26 E3 ligases.

plant biology↗

Lymphocyte-specific Protein Tyrosine Kinase Regulates Homologous Recombination (HR) DNA Repair and Targeting Enhances PARPi Utility in HR Proficient Ovarian Cancer

Poly-ADP Ribose Polymerase (PARP) targeted therapy is clinically approved for the treatment of homologous recombination (HR) repair deficient tumors. The remarkable success in treatment of HR repair deficient cancers has not translated to HR-proficient cancer. Our studies identify the mechanism of non-receptor lymphocyte-specific protein tyrosine kinase (LCK) in HR repair in endometrioid epithelial ovarian cancer (eEOC). LCK expression is induced and activation in the nucleus in response to DNA damage insult. LCK inhibition attenuates expression of RAD51, BRCA1, and BRCA2 proteins necessary for HR-mediated DNA repair, sufficient to suppress RAD51 foci formation, and augments {gamma}H2AX foci formation. Mechanistically, DNA damage leads to direct interaction of LCK with RAD51 and BRCA1 in a kinase dependent manner. Attenuation of LCK sensitized HR-proficient eEOC cells to PARP inhibitor in cell culture and pre-clinical mouse studies. These findings identify a new mechanism for expanding utility of PARP inhibitors in HR proficient ovarian cancer. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/433791v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1715c60org.highwire.dtl.DTLVardef@167cb5forg.highwire.dtl.DTLVardef@158d807org.highwire.dtl.DTLVardef@1ced201_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

Genome Warehouse: A Public Repository Housing Genome-scale Data

The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB, https://bigd.big.ac.cn/), GWH accepts both full genome and partial genome (chloroplast, mitochondrion, and plasmid) sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata including biological project and sample, and genome assembly information, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By December 2020, GWH has received 17,264 direct submissions covering a diversity of 949 species, and has released 3370 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://bigd.big.ac.cn/gwh/.

bioinformatics↗

Fucoidan but not 2'-Fucosyllactose could inhibit human norovirus replication in zebrafish larvae

Human noroviruses (hNoVs) cause heavy disease burden worldwide and there is no clinically approved vaccination or antivirals hitherto. In this study, with the use of a zebrafish larvae in vivo platform, we investigated the anti-hNoV potentials of fucoidan and 2-Fucosyllactose (2-FL). As a result, although both fucoidan and 2-FL were able to block hNoV GII.4 virus-like particle (VLPs) from binding to type A saliva as expected, only fucoidan but not 2-FL was able to inhibit the replication of hNoV GII.P16-GII.4 in zebrafish larvae, indicating the possible needs of higher molecular weights for fucosylated carbohydrates to exert anti-hNoV effect.

microbiology↗