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On page 1 showing 1 ~ 20 papers out of 28 papers

Synthesis and Characterization of Flower-like Carbon-encapsulated Fe-C Nanoparticles for Application as Adsorbing Material.

  • Lixin Zhao‎ et al.
  • Materials (Basel, Switzerland)‎
  • 2019‎

Carbon-encapsulated Fe-C (Fe-C@C) nanoparticles with a divergently flower-like morphology were successfully synthesized for application as an adsorbing material by using freeze-drying and chemical vapor deposition (CVD) methods. The Fe metallic source was first loaded onto a sodium chloride (NaCl) supporter via freeze-drying to obtain the Fe/NaCl composite powder. Then, Fe-C@C nanoparticles were synthesized in the temperature range of 300⁻450 °C via CVD of acetylene in the Fe/NaCl composite powder using Fe nanoparticles as catalysts and NaCl as supporters. Because the NaCl supporter is water-soluble, the synthesized Fe-C@C nanoparticles were easy to purify, and a high purity was obtained by simple washing and centrifugation. The optimal Fe-C@C nanoparticles, synthesized at 400 °C, possessed a unique divergently flower-like structure and a high specific surface area of 169.4 m²/g that can provide more adsorption sites for contaminants. Adsorption experiments showed that the flower-like Fe-C@C adsorbent exhibited high adsorption capacity (90.14 mg/g) and fast removal of methylene blue (MB). Moreover, the magnetic properties of the nanoparticles, with saturation magnetization of 36.544 emu/g, facilitated their magnetic separation from wastewater. Therefore, the novel flower-like Fe-C@C nanoparticles with integrated adsorptive and magnetic properties have the potential to be an effective adsorbent in dye wastewater treatment.


A transient transformation system for gene characterization in upland cotton (Gossypium hirsutum).

  • Haipeng Li‎ et al.
  • Plant methods‎
  • 2018‎

Genetically modified cotton accounts for 64% of the world's cotton growing area (22.3 million hectares). The genome sequencing of the diploid cotton progenitors Gossypium raimondii and Gossypium arboreum as well as the cultivated Gossypium hirsutum has provided a wealth of genetic information that could be exploited for crop improvement. Unfortunately, gene functional characterization in cotton is lagging behind other economically important crops due to the low efficiency, lengthiness and technical complexity of the available stable transformation methods. We present here a simple, fast and efficient method for the transient transformation of G. hirsutum that can be used for gene characterization studies.


Mitochondrial DAMPs increase endothelial permeability through neutrophil dependent and independent pathways.

  • Shiqin Sun‎ et al.
  • PloS one‎
  • 2013‎

Trauma and sepsis can cause acute lung injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) in part by triggering neutrophil (PMN)-mediated increases in endothelial cell (EC) permeability. We had shown that mitochondrial (mt) damage-associated molecular patterns (DAMPs) appear in the blood after injury or shock and activate human PMN. So we now hypothesized that mitochondrial DAMPs (MTD) like mitochondrial DNA (mtDNA) and peptides might play a role in increased EC permeability during systemic inflammation and proceeded to evaluate the underlying mechanisms. MtDNA induced changes in EC permeability occurred in two phases: a brief, PMN-independent 'spike' in permeability was followed by a prolonged PMN-dependent increase in permeability. Fragmented mitochondria (MTD) caused PMN-independent increase in EC permeability that were abolished with protease treatment. Exposure to mtDNA caused PMN-EC adherence by activating expression of adherence molecule expression in both cell types. Cellular activation was manifested as an increase in PMN calcium flux and EC MAPK phosphorylation. Permeability and PMN adherence were attenuated by endosomal TLR inhibitors. EC lacked formyl peptide receptors but were nonetheless activated by mt-proteins, showing that non-formylated mt-protein DAMPs can activate EC. Mitochondrial DAMPs can be released into the circulation by many processes that cause cell injury and lead to pathologic endothelial permeability. We show here that mitochondria contain multiple DAMP motifs that can act on EC and/or PMN via multiple pathways. This can enhance PMN adherence to EC, activate PMN-EC interactions and subsequently increase systemic endothelial permeability. Mitochondrial DAMPs may be important therapeutic targets in conditions where inflammation pathologically increases endothelial permeability.


Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2.

  • Dalang Yu‎ et al.
  • Briefings in bioinformatics‎
  • 2022‎

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.


A Survey of Rural Residents' Perception and Response to Health Risks from Hot Weather in Ethnic Minority Areas in Southwest China.

  • Haipeng Li‎ et al.
  • International journal of environmental research and public health‎
  • 2019‎

Ethnic minority areas in southwestern China are facing frequent high-temperature heatwaves. The health risk perceptions and responses of the local residents need to be investigated in order to formulate public policies to mitigate the impacts of climate change on health. In this study, a household survey was conducted in Pengshui Miao and Tujia Autonomous County of Chongqing from January to February 2019. A total of 624 local residents were sampled using the multi-stage sampling method. We used multivariate logistic regression models to explore the factors affecting risk perceptions and responses with regard to hot weather. The results showed that despite a relatively high level of risk perception, the study population had a very low level of willingness to see a doctor (24.4%), especially ethnic minority residents (17.5%). In particular, 80% of residents were aware of climate warming and 79% of residents were aware of the health risks of hot weather. Almost all survey participants reported a response to hot weather, with more than half of the participants stating that they would go somewhere cooler (58.5%) and drink more water (56.3%). Compared with the Han Chinese, ethnic minority participants had a higher perception of warm temperature (p <0.001) and associated health risks (p <0.001) but a lower perception of physical discomfort (p <0.001) and aggravated diseases (p = 0.001). The logistic models indicated that ethnic minority, residence time, outdoor working hours, and health status can significantly influence perceptions and subsequently significantly affect coping behaviors. In conclusion, our findings provide significant implications for the development of policies and health education and promotion programs for ethnic minorities in southwest China to aid them in maintaining good health during future hot weather events.


Modality-based organization of ascending somatosensory axons in the direct dorsal column pathway.

  • Jingwen Niu‎ et al.
  • The Journal of neuroscience : the official journal of the Society for Neuroscience‎
  • 2013‎

The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the "somatotopic map" model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial-lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough "somatotopic map" was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway.


New Software for the Fast Estimation of Population Recombination Rates (FastEPRR) in the Genomic Era.

  • Feng Gao‎ et al.
  • G3 (Bethesda, Md.)‎
  • 2016‎

Genetic recombination is a very important evolutionary mechanism that mixes parental haplotypes and produces new raw material for organismal evolution. As a result, information on recombination rates is critical for biological research. In this paper, we introduce a new extremely fast open-source software package (FastEPRR) that uses machine learning to estimate recombination rate [Formula: see text] (=[Formula: see text]) from intraspecific DNA polymorphism data. When [Formula: see text] and the number of sampled diploid individuals is large enough ([Formula: see text]), the variance of [Formula: see text] remains slightly smaller than that of [Formula: see text] The new estimate [Formula: see text] (calculated by averaging [Formula: see text] and [Formula: see text]) has the smallest variance of all cases. When estimating [Formula: see text], the finite-site model was employed to analyze cases with a high rate of recurrent mutations, and an additional method is proposed to consider the effect of variable recombination rates within windows. Simulations encompassing a wide range of parameters demonstrate that different evolutionary factors, such as demography and selection, may not increase the false positive rate of recombination hotspots. Overall, accuracy of FastEPRR is similar to the well-known method, LDhat, but requires far less computation time. Genetic maps for each human population (YRI, CEU, and CHB) extracted from the 1000 Genomes OMNI data set were obtained in less than 3 d using just a single CPU core. The Pearson Pairwise correlation coefficient between the [Formula: see text] and [Formula: see text] maps is very high, ranging between 0.929 and 0.987 at a 5-Mb scale. Considering that sample sizes for these kinds of data are increasing dramatically with advances in next-generation sequencing technologies, FastEPRR (freely available at http://www.picb.ac.cn/evolgen/) is expected to become a widely used tool for establishing genetic maps and studying recombination hotspots in the population genomic era.


Dynamics and Structure Formation of Confined Polymer Thin Films Supported on Solid Substrates.

  • Mujib Ur Rahman‎ et al.
  • Polymers‎
  • 2021‎

The stability/instability behavior of polystyrene (PS) films with tunable thickness ranging from higher as-cast to lower residual made on Si substrates with and without native oxide layer was studied in this paper. For further extraction of residual PS thin film (hresi) and to investigate the polymer-substrate interaction, Guiselin's method was used by decomposing the polymer thin films in different solvents. The solvents for removing loosely adsorbed chains and extracting the strongly adsorbed irreversible chains were selected based on their relative desorption energy difference with polymer. The PS thin films rinsed in chloroform with higher polarity than that of toluene showed a higher decrease in the residual film thickness but exhibited earlier growth of holes and dewetting in the film. The un-annealed samples with a higher oxide film thickness showed a higher decrease in the PS residual film thickness. The effective viscosity of PS thin films spin-coated on H-Si substrates increased because of more resistance to flow dynamics due to the stronger polymer-substrate interaction as compared to that of Si-SiOx substrates. By decreasing the film thickness, the overall effective mobility of the film increased and led to the decrease in the effective viscosity, with matching results of the film morphology from atomic force microscopy (AFM). The polymer film maintained low viscosity until a certain period of time, whereupon further annealing occurred, and the formation of holes in the film grew, which ultimately dewetted the film. The residual film decrement, growth of holes in the film, and dewetting of the polymer-confined thin film showed dependence on the effective viscosity, the strength of solvent used, and various involved interactions on the surface of substrates.


Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression.

  • Luchuan Li‎ et al.
  • Biochemical and biophysical research communications‎
  • 2015‎

Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na(+)/I(-) symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC).


The Glutathione Peroxidase Gene Family in Gossypium hirsutum: Genome-Wide Identification, Classification, Gene Expression and Functional Analysis.

  • Mingyang Chen‎ et al.
  • Scientific reports‎
  • 2017‎

The plant glutathione peroxidase (GPX) family consists of multiple isoenzymes with distinct subcellular locations, tissue-specific expression patterns and environmental stress responses. In this study, 13 putative GPXs from the genome of Gossypium hirsutum (GhGPXs) were identified and a conserved pattern among plant GPXs were exhibited, besides this they also responded to multiple environmental stresses and we predicted that they had hormone responsive cis-elements in their promoter regions. Most of the GhGPXs on expression in yeast can scavenge H2O2. Our results showed that different members of the GhGPX gene family were co-ordinately regulated under specific environmental stress conditions, and suggested the importance of GhGPXs in hormone treatments and abiotic stress responses.


Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children.

  • Yuanyuan Li‎ et al.
  • Intervirology‎
  • 2016‎

Coronavirus (CoV) infections induce respiratory tract illnesses and central nervous system (CNS) diseases. We aimed to explore the cytokine expression profiles in hospitalized children with CoV-CNS and CoV-respiratory tract infections.


Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri.

  • Guo-Dong Wang‎ et al.
  • Proceedings of the National Academy of Sciences of the United States of America‎
  • 2018‎

Tibetan frogs, Nanorana parkeri, are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation.


Inferring the demographic history and rate of adaptive substitution in Drosophila.

  • Haipeng Li‎ et al.
  • PLoS genetics‎
  • 2006‎

An important goal of population genetics is to determine the forces that have shaped the pattern of genetic variation in natural populations. We developed a maximum likelihood method that allows us to infer demographic changes and detect recent positive selection (selective sweeps) in populations of varying size from DNA polymorphism data. Applying this approach to single nucleotide polymorphism data at more than 250 noncoding loci on the X chromosome of Drosophila melanogaster from an (ancestral) African population and a (derived) European, we found that the African population expanded about 60,000 y ago and that the European population split off from the African lineage about 15,800 y ago, thereby suffering a severe population size bottleneck. We estimated that about 160 beneficial mutations (with selection coefficients s between 0.05% and 0.5%) were fixed in the euchromatic portion of the X in the African population since population size expansion, and about 60 mutations (with s around 0.5%) in the diverging European lineage.


Functional characterisation of Holothuria leucospilota Fas-associated death domain in the innate immune-related signalling pathways.

  • Haipeng Li‎ et al.
  • Innate immunity‎
  • 2020‎

In this study, the functions of Holothuria leucospilota Fas-associated death domain (HLFADD) in the innate immune-related signalling pathways were investigated. The results showed that over-expression of HLFADD in HEK293T cells could activate the transcription factors NF-κB and activator protein-1 (AP-1), and induce the secretion of downstream pro-inflammatory cytokines IL-6, IL-8 and IL-18, suggesting the involvement of the sea cucumber FADD in activating the NF-κB and c-Jun NH2-terminal kinase-dependent pathways. On the other hand, HLFADD could down-regulate the activations of NF-κB and AP-1 that induced by over-expression of H. leucospilota myeloid differentiation factor 88 (HLMyD88), which is supposed to be mediated through its interaction with HLMyD88 to keep the MyD88-dependent TLR signalling at a proper magnitude. The interaction of HLFADD and HLMyD88 were further supported by a co-immunoprecipitation assay. Moreover, HLFADD could activate transcription factor IFN regulatory factor-3 and induced the secretion of downstream IFN-α and IFN-β, indicating that the sea cucumber FADD may also activate the antiviral IFN signalling pathway. In summary, our study may give new insights on the functions of sea cucumber FADD in the innate immune-related signalling pathways.


Genome-wide analysis and characterization of F-box gene family in Gossypium hirsutum L.

  • Shulin Zhang‎ et al.
  • BMC genomics‎
  • 2019‎

F-box proteins are substrate-recognition components of the Skp1-Rbx1-Cul1-F-box protein (SCF) ubiquitin ligases. By selectively targeting the key regulatory proteins or enzymes for ubiquitination and 26S proteasome mediated degradation, F-box proteins play diverse roles in plant growth/development and in the responses of plants to both environmental and endogenous signals. Studies of F-box proteins from the model plant Arabidopsis and from many additional plant species have demonstrated that they belong to a super gene family, and function across almost all aspects of the plant life cycle. However, systematic exploration of F-box family genes in the important fiber crop cotton (Gossypium hirsutum) has not been previously performed. The genome-wide analysis of the cotton F-box gene family is now possible thanks to the completion of several cotton genome sequencing projects.


Comparative Transcriptomic Analysis Reveals Diverse Expression Pattern Underlying Fatty Acid Composition among Different Beef Cuts.

  • Tianliu Zhang‎ et al.
  • Foods (Basel, Switzerland)‎
  • 2022‎

Beef is an important dietary source of quality animal proteins and amino acids in human nutrition. The fatty acid composition is one of the indispensable indicators affecting nutritional value of beef. However, a comprehensive understanding of the expression changes underlying fatty acid composition in representative beef cuts is needed in cattle. This study aimed to characterize the dynamics of fatty acid composition using comparative transcriptomic analysis in five different type of beef cuts. We identified 7545 differentially expressed genes (DEGs) among 10 pair-wise comparisons. Co-expression gene network analysis identified two modules, which were significantly correlated with 2 and 20 fatty acid composition, respectively. We also identified 38 candidate genes, and functional enrichment showed that these genes were involved in fatty acid biosynthetic process and degradation, PPAR, and AMPK signaling pathway. Moreover, we observed a cluster of DEGs (e.g., SCD, LPL, FABP3, and PPARD) which were involved in the regulation of lipid metabolism and adipocyte differentiation. Our results provide some valuable insights into understanding the transcriptome regulation of candidate genes on fatty acid composition of beef cuts, and our findings may facilitate the designs of genetic selection program for beneficial fatty acid composition in beef cattle.


The Activation of Ti-Zr-V-Hf Non-Evaporable Getter Films with Open-Cell Copper Metal Foam Substrates.

  • Jie Wang‎ et al.
  • Materials (Basel, Switzerland)‎
  • 2020‎

Secondary electron emission (SEE) inhibition and vacuum instability are two important issues in accelerators that may induce multiple effects in accelerators, such as power loss and beam lifetime reduction. In order to mitigate SEE and maintain high vacuum simultaneously, open-cell copper metal foam (OCMF) substrates with Ti-Zr-V-Hf non-evaporable getter (NEG) coatings are first proposed, and the properties of surface morphology, surface chemistry and secondary electron yield (SEY) were analyzed for the first time. According to the experimental results tested at 25 °C, the maximum SEY (δmax) of OCMF before and after Ti-Zr-V-Hf NEG film deposition were 1.25 and 1.22, respectively. The XPS spectra indicated chemical state changes of the metal elements (Ti, Zr, V and Hf) of the Ti-Zr-V-Hf NEG films after heating, suggesting that the NEG films can be activated after heating and used as getter pumps.


SERS Hotspot Engineering by Aerosol Self-Assembly of Plasmonic Ag Nanoaggregates with Tunable Interparticle Distance.

  • Haipeng Li‎ et al.
  • Advanced science (Weinheim, Baden-Wurttemberg, Germany)‎
  • 2022‎

Surface-enhanced Raman scattering (SERS) is a powerful sensing technique. However, the employment of SERS sensors in practical applications is hindered by high fabrication costs from processes with limited scalability, poor batch-to-batch reproducibility, substrate stability, and uniformity. Here, highly scalable and reproducible flame aerosol technology is employed to rapidly self-assemble uniform SERS sensing films. Plasmonic Ag nanoparticles are deposited on substrates as nanoaggregates with fine control of their interparticle distance. The interparticle distance is tuned by adding a dielectric spacer during nanoparticle synthesis that separates the individual Ag nanoparticles within each nanoaggregate. The dielectric spacer thickness dictates the plasmonic coupling extinction of the deposited nanoaggregates and finely tunes the Raman hotspots. By systematically studying the optical and morphological properties of the developed SERS surfaces, structure-performance relationships are established and the optimal hot-spots occur for interparticle distance of 1 to 1.5 nm among the individual Ag nanoparticles, as also validated by computational modeling, are identified for the highest signal enhancement of a molecular Raman reporter. Finally, the superior stability and batch-to-batch reproducibility of the developed SERS sensors are demonstrated and their potential with a proof-of-concept practical application in food-safety diagnostics for pesticide detection on fruit surfaces is explored.


Genome-wide analysis of pseudogenes reveals HBBP1's human-specific essentiality in erythropoiesis and implication in β-thalassemia.

  • Yanni Ma‎ et al.
  • Developmental cell‎
  • 2021‎

The human genome harbors 14,000 duplicated or retroposed pseudogenes. Given their functionality as regulatory RNAs and low conservation, we hypothesized that pseudogenes could shape human-specific phenotypes. To test this, we performed co-expression analyses and found that pseudogene exhibited tissue-specific expression, especially in the bone marrow. By incorporating genetic data, we identified a bone-marrow-specific duplicated pseudogene, HBBP1 (η-globin), which has been implicated in β-thalassemia. Extensive functional assays demonstrated that HBBP1 is essential for erythropoiesis by binding the RNA-binding protein (RBP), HNRNPA1, to upregulate TAL1, a key regulator of erythropoiesis. The HBBP1/TAL1 interaction contributes to a milder symptom in β-thalassemia patients. Comparative studies further indicated that the HBBP1/TAL1 interaction is human-specific. Genome-wide analyses showed that duplicated pseudogenes are often bound by RBPs and less commonly bound by microRNAs compared with retropseudogenes. Taken together, we not only demonstrate that pseudogenes can drive human evolution but also provide insights on their functional landscapes.


Moderate mutation rate in the SARS coronavirus genome and its implications.

  • Zhongming Zhao‎ et al.
  • BMC evolutionary biology‎
  • 2004‎

The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood.


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