Biology subjects

Yuan, L.

Publications and source records attributed to Yuan, L..

At least 109 records · Page 6Linked to original sources

bioRxiv2021

ADP-ribose triggers neuronal ferroptosis via metabolic orchestrating

Hyperactivation of NAD+-consuming pathways frequently occurs in neurological diseases, however therapies replenishing NAD+ levels show limited therapeutic efficacy, indicating more complex underlying pathophysiology. Here, we delineate a pathogenic link between ADP-ribose --a product of NAD+ consumption--and a metabolic rewiring-dependent form of neuronal ferroptosis. We demonstrate that oxidative stress induces neurons to produce ADP-ribose through the PARP1-PARG axis. ADP-ribose directly binds and inhibits the equilibrative nucleoside transporter ENT2, remodeling de novo purine and pyrimidine synthesis by hyperactivating the inosine-hypoxanthine-xanthine oxidase and glutamine-dihydroorotate-dihydroorotate dehydrogenase axes. This overproduces superoxide radicals and drives lipid peroxidation and neuronal ferroptosis. Elevated ADP-ribose levels were observed in neurological disease models, and acute ADP-ribose exposure severely reduced mouse brain neurons in vivo. Critically, interventions blocking ADP-ribose signaling alleviated cognitive decline in mouse intracerebral hemorrhage models. Our findings characterize ADP-ribose signaling as linking NAD+ consumption to neuronal ferroptosis, and provide a theraputic strategy for neuropathologies involving NAD+ consumption and oxidative stress.

neuroscience↗

bioRxiv2021

Nasal BCG Exposure Accelerates Dural Lymphatics Development via Macrophages' Role in Newborn Mice

The dural lymphatics develop mainly during the first postnatal month. Lymphatics may be shaped by immune activation when bacterial infection happens. BCG, a strong immune activator, is widely injected to newborns. Moreover, human beings are nasally exposed in daily life to bacterial stimuli. These background prompted us to investigate whether neonatal BCG injection combined with nasally exposure exerts an influence on dural lymphatics develop. Here, mice received a single dose intracutaneous (i.c.) BCG injection immediately after birth followed by repeated nasal BCG challenge once a day (i.c./nasal group). These mice had an accelerated dural lymphatics growth and increased levels of several cytokines and VEGFR-3. Furthermore, macrophages were identified as a key mediator of these alterations. Mice that received mere one dose i.c. BCG injection showed no significant alterations in these indexes. Additionally, mere repeated nasal BCG challenge induced similar effects to i.c./nasal challenge but with a slighter extent. Taken together, these findings show that repeated nasal BCG vaccination accelerates dural lymphatics development in neonatal mice, especially in the presence of neonatal i.c. BCG injection.

neuroscience↗

bioRxiv2021

Using mixed-effects modeling to estimate decay kinetics of response to SARS-CoV-2 infection

The duration of natural immunity in response to SARS-CoV-2 is a matter of some debate in the literature at present. For example, in a recent publication characterizing SARS-CoV-2 immunity over time, the authors fit pooled longitudinal data, using fitted slopes to infer the duration of SARS-CoV-2 immunity. In fact, such approaches can lead to misleading conclusions as a result of statistical model-fitting artifacts. To exemplify this phenomenon, we reanalyzed one of the markers (pseudovirus neutralizing titer) in the publication, using mixed-effects modeling, a methodology better suited to longitudinal datasets like these. Our findings showed that the half-life was both longer and more variable than reported by the authors. The example selected by us here illustrates the utility of mixed-effects modeling in provide more accurate estimates of the duration and heterogeneity of half-lives of molecular and cellular biomarkers of SARS-CoV-2 immunity.

immunology↗

bioRxiv2020

Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

microbiology↗

bioRxiv2020

Sewage-Borne Pathogens and Indigenous Denitrifiers are Active and Key Multi-Antibiotic Resistant Players in Wastewater Treatment Plants

The global rise and spread of antibiotic resistance greatly challenge the treatment of bacterial infections. Wastewater treatment plants (WWTPs) harbor and discharge antibiotic resistance genes (ARGs) as environmental contaminants. However, the knowledge gap on the host identity, activity and functionality of ARGs limits transmission and health risk assessment of WWTPs resistome. Hereby, a genome-centric quantitative metatranscriptomic approach was exploited to realize high-resolution qualitative and quantitative analyses of bacterial hosts of ARGs (i.e., multi-resistance, pathogenicity, activity and niches) throughout 12 urban WWTPs. We found that [~]45% of 248 recovered genomes expressed ARGs against multiple classes of antibiotics, among which bacitracin and aminoglycoside resistance genes in Proteobacteria was the most prevalent scenario. Both potential pathogens and indigenous denitrifying bacteria were transcriptionally active hosts of ARGs. The almost unchanged relative expression levels of ARGs in the most resistant populations (66.9%) and the surviving ARG hosts including globally emerging pathogens (e.g., Aliarcobacter cryaerophilus) in treated WWTP effluent prioritizes future examination on the health risks related with resistance propagation and human exposure in the receiving environment.

microbiology↗

bioRxiv2020

An interactive viral genome evolution network analysis system enabling rapid large-scale molecular tracing of SARS-CoV-2

Comprehensive analyses of viral genomes can provide a global picture on SARS-CoV-2 transmission and help to predict the oncoming trends of pandemic. This molecular tracing is mainly conducted through extensive phylogenetic network analyses. However, the rapid accumulation of SARS-CoV-2 genomes presents an unprecedented data size and complexity that has exceeded the capacity of existing methods in constructing evolution network through virus genotyping. Here we report a Viral genome Evolution Network Analysis System (VENAS), which uses Hamming distances adjusted by the minor allele frequency to construct viral genome evolution network. The resulting network was topologically clustered and divided using community detection algorithm, and potential evolution paths were further inferred with a network disassortativity trimming algorithm. We also employed parallel computing technology to achieve rapid processing and interactive visualization of >10,000 viral genomes, enabling accurate detection and subtyping of the viral mutations through different stages of Covid-19 pandemic. In particular, several core viral mutations can be independently identified and linked to early transmission events in Covid-19 pandemic. As a general platform for comprehensive viral genome analysis, VENAS serves as a useful computational tool in the current and future pandemics.

evolutionary biology↗

bioRxiv2020

Reverse-transcription recombinase-aided amplification assay for H5 subtype avian influenza virus

The H5 subtype Avian Influenza Virus has caused huge economic losses to the poultry industry and is a threat to human health. A rapid and simple test is needed to confirm infection in suspected cases during disease outbreaks. In this study, we developed a reverse-transcription recombinase-aided amplification assay for the detection of H5 subtype avian influenza virus. Assays were performed at a single temperature (39{degrees}C), and the results were obtained within 20 min. The assay showed no cross-detection with Newcastle disease virus or infectious bronchitis virus. The analytical sensitivity was 103 RNA copies per reaction at a 95% confidence interval according to probit regression analysis, with 100% specificity. Compared with published reverse-transcription quantitative real-time polymerase chain reaction assays, the {kappa} value of the reverse transcription recombinase-aided amplification assay in 365 avian clinical samples was 0.970 (p < 0.001). The sensitivity for avian clinical sample detection was 94.44% (95%CI, 70.63% - 99.71%), and the specificity was 100% (95%CI, 98.64% - 100%). These results indicated that our reverse-transcription recombinase-aided amplification assay may be a valuable tool for detecting H5 subtype avian influenza virus.

molecular biology↗

bioRxiv2020

Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors

The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.

microbiology↗

bioRxiv2020

Distinct growth stages shaped by an interplay of deterministic and neutral processes are indispensable for functional anammox biofilms

Complex microbial biofilms orchestrating mainstream anaerobic ammonium oxidation (anammox) represent one of the most promising energy-efficient mechanisms of fixed nitrogen elimination from anthropogenic waste waters. However, little is known about the ecological processes that are driving microbial community assembly leading to functional anammox biofilms in engineered ecosystems. Here, we use fluorescence in situ hybridization and 16S rRNA sequencing combined with network modelling to elucidate the contribution of stochastic and deterministic processes during anammox biofilm development from first colonization to maturation in a carrier-based anammox reactor. We find that distinct stages of biofilm development emerge naturally in terms of structure and community composition. These stages are characterized by dynamic succession and an interplay of stochastic and deterministic processes. The staged process of biofilm establishment appears to be the prerequisite for the anticipated growth of anammox bacteria and for reaching a biofilm community structure with the desired metabolic capacities. We discuss the relevance of this improved understanding of anammox community ecology and biofilm development concerning its practical application in the start-up and configuration of anammox biofilm reactors.

microbiology↗

bioRxiv2020

Effect of allelopathy on plant performance

Allelopathy (i.e. chemical interactions between plants) is known to affect individual performance, community structure and plant invasions. Yet, a quantitative synthesis is lacking. We performed a meta-analysis of 385 studies that measured allelopathic effects of one species (allelopathy plant) on another species or itself (test plant). Overall, allelopathy reduced plant performance by 25%, but the variation in allelopathy was high. Type of method affected allelopathic effect. Compared to leachates, allelopathy was more negative when residues of allelopathy plants were applied, and less negative when soil conditioned by allelopathy plants was applied. The negative effects of allelopathy diminished with study duration, and increased with concentrations of leachates or residues. Although allelopathy was not significantly related to life span, life form and domestication of the interacting plants, it became more negative with increasing phylogenetic distance. Moreover, native plants suffered more negative effects from leachates of naturalized alien plants than of other native plants. Our synthesis reveals that allelopathy could contribute to success of alien plants. The negative relationship between phylogenetic distance and allelopathy indicates that allelopathy might drive coexistence of close-related species (i.e. convergence) or dominance of single species.

ecology↗

bioRxiv2019

Testosterone Changes in Female Pandas in Estrus

Currently, the majority of giant panda breeding is carried out by cage-mating or artificial insemination based on estrogen levels and behavior in female pandas. However, studies have shown that testosterone levels both in women and in non-human primate females have a significant effect on the desire to mate. In this study, we wanted to explain how testosterone levels of female giant pandas would change during estrous. In this study, 23 accounts of rutting were recorded in 10 female pandas from 2009 to 2012. Changes in urinal testosterone levels were monitored and compared with estradiol values. Our data showed that, for female pandas in estrus, testosterone levels after the estradiol peak was significantly higher than before, and the testosterone peak occurred 4 days after the estradiol peak. Furthermore, testosterone and estradiol level were only significantly correlated after peak estradiol levels peaked, and not before. Finally, out findings suggest that testosterone could help us better understand hormone variation during panda estrus, as well as help aid in the natural breeding of pandas.

zoology↗

bioRxiv2019

Protein adlayer thickness on colloidal nanoparticle determined by Rayleigh-Gans-Debye approximation

Reference materials (RM)-assisted Rayleigh-Gans-Debye approximation (rm-RGDA) has been developed and used to in situ determine the size and thickness of the adlayer on the particles in solution. The particle size determined by rm-RGDA is quite close to that measured by electron microscopy but significantly smaller than that measured by DLS. The BSA adlayer absorbed on PS50, PS100 and SiO2 NPs is 3.3, 0.9 and 1.2 nm, respectively, and close to those observed by SEM, which is 4.6, 1.3 and 3.8 nm, respectively. The FTIR analysis results show that the BSA absorbed on larger particles or hydroxyl-abundant surface, e.g. PS100 and SiO2 NPs can lose its secondary structure, e.g. -helix, to a great extent and that absorbed on a more curve surface, e.g. smaller PS50 particles can largely preserve its secondary structure as its free state. The measurement results show the curvature of the NPs is closely related to the structure change of the adsorbed protein. This method provide a facile and new approach to measure the size and its adlayer change of the hybrid and core-shell structured nanoparticles in a wide range of wavelength. SIGNIFICANCEQuantitative study on the adsorption of the protein on colloidal nanoparticles is an important approach to understand the biophysical effect, compared with other ex situ methods such as TEM and SEM, where the specimen are undergone pre-processing and no longer the original state in measurement. It is, therefore, a big challenge. In order to cope with this challenge, UV-vis based RGDA has been developed and applied to in situ measure the size of the dispersed colloidal nanoparticles and their protein adlayer thickness, where the protein adlayer thickness on the colloidal nanoparticles can be easily determined. We believe this method provide a facile and sensitive way to in situ measure the dimension change of hybrid colloidal nanoparticles.

biophysics↗

bioRxiv2019

New genotype invasion of dengue virus serotype 1 drove massive outbreak in Guangzhou, China

BackgroundDengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. However, the associations of DENV genes with epidemic scale have not been extensively examined. Here, we assessed new genotype invasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks.\n\nMethodology/Principal FindingsWe used DENV-1 strains isolated from sera of dengue cases from 2002 to 2016 in Guangzhou for complete genome sequencing. A neighbor-joining phylogenetic tree was constructed to elucidate the genotype characteristics and determine if new genotype invasion correlated with major outbreaks. In our study, a new genotype invasion event was observed during each significant outbreak period in 2002-2003, 2006-2007 and 2013-2014. Genotype II was the main epidemic genotype in 2003 and before. Invasion of genotype I in 2006 caused an unusual outbreak with 765 cases (relative risk (RR)=16.24, 95% confidence interval (CI) =12.41-21.25). At the middle and late stages of the 2013 outbreak, genotype III was introduced to Guangzhou as a new genotype invasion responsible for 37340 cases with RR 541.73 (95%CI=417.78-702.45), after which genotypes I and III began co-circulating. Base mutations occurred after new genotype invasion, and the gene sequence of NS3 protein had the lowest average similarity ratio (99.82%), followed by the gene sequence of E protein (99.86%), as compared to the 2013 strain.\n\nConclusions/SignificanceGenotype replacement and co-circulation of multiple DENV-1 genotypes were observed. New genotype invasion was highly correlated with local unusual outbreaks. In addition to DENV-1 genotype I in the unprecedented outbreak in 2014, new genotype invasion by DENV-1 genotype III occurred in Guangzhou.\n\nAuthor SummaryNew genotype invasion of dengue virus highly correlates with the massive outbreaks. In this study, we examined the association of the genotype of dengue virus serorype 1 (DENV-1) from human cases through complete genome sequencing with outbreak scale during 2002 and 2016 in Guangzhou, China. It was observed that genotype replacement and co-circulation of multiple genotypes occurred. Most importantly, it indicated that new genotype invasion was highly related with local unusual outbreaks in major outbreak periods in 2002-2003, 2006-2007 and 2013-2014. DENV-1 genotype II was the main epidemic genotype in 2003 and before. Invasion of genotype I in 2006 caused an unusual outbreak with 765 cases reported. In addition to genotype I circulation, new genotype invasion by genotype III was the key determinant for the 2014 massive outbreak reaching the highest number of cases with 37340. Furthermore, base mutations appeared after genotype III invasion, and the gene sequence of NS3 protein had the lowest average similarity ratio, followed by the gene sequence of E protein, as compared to the 2013 strain.

epidemiology↗

bioRxiv2019

Whole-genome sequencing of 128 camels across Asia provides insights into origin and migration of domestic Bactrian camels

The domestic Bactrian camels were treated as the principal means of locomotion between the eastern and western cultures in history. To address the question of their origin, we performed whole-genome sequencing of 128 camels across Asia, including representative populations of domestic Bactrian camels from the Mongolian Plateau to the Caspian Sea, as well as the extant wild Bactrian camels and dromedaries. The domestic and wild Bactrian camels showed remarkable genetic divergence since they were split from dromedaries, confirming they were separated species. The wild Bactrian camels made also little contribution to the ancestry of domestic ones. Among the domestic Bactrian camels, those from Iran exhibited the largest genetic distance from others, and were the first population to separate in the phylogeny. Although evident admixture was observed between domestic Bactrian camels and dromedaries living around the Caspian Sea, the large genetic distance and basal position of Iranian Bactrian camels could not be explained by introgression alone. Taken together, our study favored the Iranian origin of domestic Bactrian camels, which were then immigrated eastward to Mongolia where the native wild Bactrian camels inhabited. This study illustrated the complex genomic landscape of migration underlying domestication in Bactrian camels.

genomics↗

bioRxiv2019

Inhibition of ADORA1 attenuates hepatic steatosis by gut microbiota-derived acetic acid from Astragalus polysaccharides

The authors have withdrawn this manuscript, because some data could not be replicated. During the process of subsequent revision of the manuscript, we separated the data into two parts. The majority data of the preprint draft, the anti-NAFLD effect of Astragalus polysaccharides (APS) in mice and the contribution of gut microbiota, were independently published in 2021 after substantial revision (doi: https://doi.org/10.1080/19490976.2021.1930874). However, the data on figure 6 (about ARs inhibitors DPCPX orally ameliorating NAFLD in mice, and Adora1 si-RNA data in vitro) could not be fully replicated in subsequent experiments. The most probable reason might be due to the batch differences of mice / cells, or other undetermined factors during experiment. Moreover, we have carried out in-depth studies on the exact role of hepatic A1R on NAFLD formation, which is opposite to our prior assumption. Therefore, we do not wish this work to be cited as reference for the project. We apologize for any inconvenience caused to our readers. Any questions can be addressed to first/corresponding author.

physiology↗

bioRxiv2019

Primary pterygium was not associated with corneal endothelial cell decrease in a rural Chinese population

PurposeTo investigate the corneal endothelial cell density (ECD) in eyes with primary pterygium.\n\nMethodsWe first conducted a retrospective study to compare the ECD between 1670 eyes with primary pterygium and 4060 eyes without pterygium. Then we designed a prospective study to confirm the critical findings of the retrospective study in 95 patients with unilateral primary pterygium.\n\nResultsIn the retrospective study, the mean preoperative ECD in eyes with primary ptergyium (2453{+/-}306 cells/mm2) was statistically significantly lower than those in eyes without pterygium (2529{+/-}313 cells/mm2, P<0.0001). However, the difference was minor (76 cells/mm2, 3.1%). In the prospective study, the mean ECD in eyes with unilateral primary pterygium (2480{+/-}263 cells/mm2) was not significantly different from those in the contralateral eyes (2527{+/-}277 cells/mm2, P=0.20). The hexagonality (P=0.10) or coefficient of variation of size (P=0.15) of corneal endothelial cells was not significantly different between eyes with pterygium and the contralateral eyes.\n\nConclusionPrimary pterygium may not be associated with ECD decrease in our study cohort.

epidemiology↗

bioRxiv2019

Rice bran supplementation modulates growth, microbiome and metabolome in weaning infants: a clinical trial in Nicaragua and Mali

Rice bran supplementation provides nutrients, prebiotics and phytochemicals that enhance gut immunity, reduce enteric pathogens in mice and diarrhea in neonatal pigs, and warranted attention for improvement of environmental enteric dysfunction (EED) in children at risk. EED is a condition that drives childhood stunting via intestinal dysbiosis and impaired nutrient metabolism. This study investigated effects of rice bran supplementation on growth, EED biomarkers, gut microbiome and metabolome in weaning infants from 6 to 12 months old in Nicaragua and Mali. Healthy infants were randomized to a control group or rice bran group that received daily supplementation at increasing doses each month. Stool microbiomes were characterized using 16S rDNA amplicon sequencing. Stool metabolomes were analyzed using ultra-high-performance liquid-chromatography tandem mass-spectrometry. Statistical comparisons were completed at 6, 8, and 12 months of age. Daily consumption of rice bran was safe and feasible for infant growth, decreasing alpha-1 antitrypsin levels, and modulating gut microbiome and metabolome when compared to control. Rice bran merits investigation as a practical intervention strategy that could decrease EED prevalence and risk for children from low- and middle-income countries where rice is grown as a staple food, and bran is used as animal feed or wasted. One Sentence SummaryDietary rice bran supplementation during infant weaning from 6-12 months of age improved growth outcomes, modulated environmental enteric dysfunction biomarkers, and supported metabolism by the gut microbiome. The authors declare no competing financial or non financial interests to disclose as defined by Nature Research. There are also no other interests that might be perceived to influence the results and/or discussion reported in this paper. Correspondence and requests for materials should be addressed to Dr. Elizabeth Ryan (e.p.ryan@colostate.edu).

clinical trials↗

bioRxiv2019

Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin {beta}4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. Specific ITGB4 deficiency in AECs induces exaggerated Th2 responses, severe allergen-induced airway inflammation and airway hyperresponsiveness (AHR) in mouse model of allergic asthma. However, the underlying mechanisms remain unexplored. In this study, we determine the role of ITGB4 of AECs in the regulation of Th2 response and in the induction of asthma and identify the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated Th2 cells infiltration, inflammation and AHR and higher production of CCL17 in HDM treated mice. ITGB4-regulated CCL17 production in AECs was regulated by EGFR, ERK and NF-{kappa}B pathways. EFGR-antagonist treatment or the neutralization of CCL17 by antibody inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated that ITGB4 of AECs negatively regulates the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway.

immunology↗