Biology subjects

Zhan, W.

Publications and source records attributed to Zhan, W..

4 recordsLinked to original sources

bioRxiv2021

Artemisinin-based hybrids produce intracellular proteasome inhibitors that overcome resistance in Plasmodium falciparum

Artemisinin resistant Plasmodium falciparum (Pf) is spreading despite combination chemotherapy (ACT). Here we report the design of artezomibs, single-molecule hybrids of an artemisinin and a Pf-selective proteasome inhibitor. Artezomibs exert a novel mode of action inside the malaria parasites. The artemisinin component covalently modifies parasite proteins, which become substrates of the Pf proteasome. The proteasomal degradation products that bear the proteasome inhibitor component of the hybrid then inhibit Pf proteasomes, including those with mutations that reduce binding affinity of the proteasome inhibitor component on its own. We demonstrated that artezomibs circumvent both artemisinin resistance conferred by Kelch13 polymorphism and resistance to the proteasome inhibitor associated with mutations in Pf proteasomes. This mode of action may enable the use of a single molecule with one pharmacokinetic profile to prevent the emergence of resistance.

microbiology↗

bioRxiv2021

The First High-Quality Reference Genome of Sika Deer Provides Insights for High-Tannin Adaptation

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement in the elucidation of the genomics of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of UGT genes in a subfamily. The first chromosome-level assembly and genetic characterization of the tolerance toa highly toxic diet suggest that the sika deer genome will serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

genomics↗

bioRxiv2020

Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming

Degeneration of retinal ganglion cells (RGCs) and their axons underlies vision loss in glaucoma and various optic neuropathies. There are currently no treatments available to restore lost vision in patients affected by these diseases. Regenerating RGCs and reconnecting the retina to the brain represent an ideal therapeutic strategy; however, mammals do not have a reservoir of retinal stem/progenitor cells poised to produce new neurons in adulthood. Here, we regenerated RGCs in adult mice by direct lineage reprogramming of retinal interneurons. We successfully converted amacrine and displaced amacrine interneurons into RGCs, and observed that regenerated RGCs projected axons into brain retinorecipient areas. They convey visual information to the brain in response to visual stimulation, and are able to transmit electrical signals to postsynaptic neurons, in both normal animals and in a diseased model. The generation of functional RGCs in adult mammals points to a therapeutic strategy for vision restoration in patients.

neuroscience↗

bioRxiv2019

Transcriptome analysis of the Larimichthys polyactis under heat and cold stress

The small yellow croaker (Larimichthys polyactis) is an important marine economic fish that is widely distributed in the East Sea, Yellow Sea and Bohai of China. However, the wild populations of small yellow croaker are severely depleted, and there is currently a developing large-scale artificial propagation of this fish for aquaculture. However, the current variety of small yellow croaker that is cultivated is not capable to coping with large fluctuations in temperature. Therefore, it is important to understand the molecular mechanisms that are activated in response to temperature stress in the small yellow croaker. Here, we conducted transcriptomic analysis of the liver of small yellow croaker under heat and cold stress. A total of 270,844,888, 265,727,006 and 259,666,218 clean reads were generated from heat temperature group, low temperature group and control group, respectively, and comparing expression of genes in these transcriptomes,10,878 unigenes that were differential expressed were identified. Sixteen of the differentially expressed unigenes were validated by qRT-PCR. Pathway enrichment analysis identified that the ER pathway, immune signaling pathway and metabolic response pathway were affected by temperature stress. The results of this study provide a comprehensive overview of temperature stress-induced transcriptional patterns in liver tissues of the small yellow croaker. In addition, these results can guide future molecular studies of heat and cold stress response in this species for improving the stock used for aquaculture.

physiology↗