Biology subjects

Zhong, N.

Publications and source records attributed to Zhong, N..

23 records · Page 2Linked to original sources

bioRxiv2020

Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients

As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.

genomics↗

bioRxiv2020

In vitro activities of the tetrazole SHR8008 compared to itraconazole and fluconazole against Candida and Cryptococcus species

Candida and Cryptococcus are the main pathogens of clinical fungal infection associated with high morbidity and mortality. SHR8008 (in fact, this is the only official name in China and it is called VT-1161 by FDA) is a novel tetrazole agent that selectively inhibits fungal CYP51A compared to mammalian cytochrome P450 enzymes to achieve a better antifungal effect. The in vitro activities of SHR8008 and its comparators itraconazole and fluconazole were determined in 127 Candida and 50 Cryptococcus strains isolated from Chinese patients in the last 2 years by Invasive Fungal Infection Group. The MICs of SHR8008 and other triazoles were measured by the Clinical and Laboratory Standards Institute guidelines M27-E4. For Candida spp., SHR8008 (geometric mean MIC=0.078 g/mL) was 6.5-fold and 11.2-fold more potent than itraconazole and fluconazole, respectively. There is a good correlation of MICs between SHR8008 and itraconazole/fluconazole. The MIC values of SHR8008 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, while for Candida albicans and Candida parapsilosis, the differences between SHR8008 and fluconazole were not statistically significant, either. For Cryptococcus spp., SHR8008 (geometric mean MIC=0.024 g/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven Cryptococcus neoformans isolates with elevated fluconazole MICs ([≥]8g/mL based on the MIC90 value for this azole), SHR8008 maintained potent activity, with MICs ranging between 0.031 and 0.5 g/mL. The results showed that tetrazole SHR8008 was more promising in the treatment of Candida and Cryptococcus infection than itraconazole and fluconazole.

microbiology↗

bioRxiv2020

In-depth 15 H7N9 Human Serum Proteomics Profiling Study

BackgroundHuman infection by avian influenza viruses is characterized by rapid development of acute respiratory distress and severe pneumonia. However, the underlying host response leading to this severe outcome is not well studied. MethodsWe conducted mass spectrometry-based serum proteome profiling on 10 healthy controls and 15 H7N9 infected cases with two time points and carried out statistical and biology functional enrichment analysis. ResultsIn total, we identified 647 proteins, 273 proteins were only found in H7N9 infected cases which might generate from cell leakage/death (apoptosis and/or necrosis) and identified 50 proteins with statistically significant difference between healthy control and H7N9 infected cases from 168 qualified proteins. We also found that M1 and PB2 tightly associated with the hosts HSPA8 (P11142, p=0.0042) which plays an important role in the protein quality control system. ConclusionsH7N9 infection may increase cell programmed/unprogrammed cell death, and we suggested that upregulated extracellular HSPA8 may suppress the H7N9 virion replication via activation amyloid-beta binding network.

molecular biology↗

bioRxiv2019

TeraVR Empowers Precise Reconstruction of Complete 3-D Neuronal Morphology in the Whole Brain

Neuron morphology is recognized as a key determinant of cell type, yet the quantitative profiling of a mammalian neurons complete three-dimensional (3-D) morphology remains arduous when the neuron has complex arborization and long projection. Whole-brain reconstruction of neuron morphology is even more challenging as it involves processing tens of teravoxels of imaging data. Validating such reconstructions is extremely laborious. We developed TeraVR, an open-source virtual reality annotation system, to address these challenges. TeraVR integrates immersive and collaborative 3-D visualization, interaction, and hierarchical streaming of teravoxel-scale images. Using TeraVR, we produced precise 3-D full morphology of long-projecting neurons in whole mouse brains and developed a collaborative workflow for highly accurate neuronal reconstruction.

neuroscience↗

bioRxiv2018

Exploring morphological motifs for a single neuron based on multiple 3D reconstructions

The morphology of individual neurons is useful to study structures and functions of nervous system. Researchers have invented many semi or fully automatic tracing methods to efficiently generate a reconstruction from a single neuron. Different tracing methods have different design principles, and could produce different reconstructions. However, the \"common substructures\" of various reconstructions, called morphological motifs, should be highly reliable. In this work, we propose a Vaa3D based framework to explore morphological motifs of 3D reconstructions from a single neuron. The framework contains four steps: (1) resampling and sorting each reconstruction according to a standard reconstruction, such as a gold standard reconstruction, consensus reconstruction or a certain reliable reconstruction; (2) applying local alignment algorithm for each pair of the standard reconstruction and a reconstruction, or each pair of two reconstructions; (3) constructing overlaps based on selected points in local alignment pairs; (4) obtaining morphological motifs by post-processing these overlaps. Under the proposed framework, three methods were implemented and tested on a dataset of 73 fruitfly neurons released by the BigNeuron project (http://bigneuron.org), which contains a gold standard reconstruction, a consensus reconstruction and about 40 automatic reconstructions for each neuron. We quantitatively evaluated these three methods to choose reliable morphological motifs.

bioinformatics↗