Biology subjects

Lv, X.

Publications and source records attributed to Lv, X..

46 records · Page 3Linked to original sources

bioRxiv2020

Ciprofloxacin Resistance in Hospital and Community-acquired Urinary Tract Infections by Escherichia coli: A Systematic Review and Meta-analysis

In recent years, antimicrobial resistance has been increasingly reported. One main concern is the resistance of gram-negative bacteria like E. coli to ciprofloxacin (fluoroquinolones). Gram-negative bacteria are the main cause of community and hospital-acquired urinary tract infections (UTI). We aimed to review and analyze the data on ciprofloxacin resistance in hospital and community-acquired UTI. A literature search of three electronic databases (PubMed, Medline, and Cochrane) was performed. We considered the papers that were published from January 2004 to May 2019. The search yielded a total of 16097 studies besides 31 studies from a manual search. Filtering yielded 1297 relevant full-text papers. Eighty-three papers, equivalent of 99 cohorts, were finally included in this systematic review and in the analysis. The analysis results suggest that pooled ciprofloxacin resistance for community and hospital-acquired E. coli UTI is 0.27 (95% CI 0.246-0.303) and 0.30 (95% CI 0.22-0.38), respectively. Pooled resistance rates according to regions are 0.43 (95% CI 0.31-0.54) for Asia ensued by Africa 0.31 (95% CI 0.22-0.35), the Middle East 0.21(95% CI 0.13-0.30), Europe 0.18 (95% CI 0.13-0.22), and Australia 0.06 (95% CI 0.04-0.08). The pooled estimates revealed that ciprofloxacin resistance was higher in developing countries compared to that in developed countries, 0.35 (95% CI 0.30-0.40) and 0.13 (95% CI 0.10-0.16), respectively. Finally, plotting resistance over time deemed statistically significant (n= 79, r= 0.29, p= 0.038). Our findings suggest that ciprofloxacin resistance among UTI patients is a highly prevalent and serious issue. The suggested risks are low-income, acquiring hospital infection, and falling in highly-vulnerable regions like Asia and Africa. We also shed light on some approaches to correct the perception of patients and general practitioners (GPs) for antibiotic usage. We also suggest ideas to impede the progress of the post-antibiotic era in countries known for high antibiotic resistance.

microbiology↗

bioRxiv2020

Tracing the origin of a new organ by inferring the genetic basis of rumen evolution

The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers. We used 897 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen origin and evolution. Comparative analyses reveal that the rumen and the first-chamber stomachs of camels and cetaceans shared a common tissue origin from the esophagus. The rumen recruited genes from other tissues/organs and up-regulated many esophagus genes to aquire functional innovations involving epithelium absorption, improvement of the ketone body metabolism and regulation of microbial community. These innovations involve such genetic changes as ruminant-specific conserved elements, newly evolved genes and positively selected genes. Our in vitro experiements validate the functions of one enhancer, one positively selected gene and two newly evolved antibacterial genes. Our study provides novel insights into the origin and evolution of a complex organ.

evolutionary biology↗

bioRxiv2020

Molecular surveillance of HIV, HBV, and HCV amongst blood donors in five Chinese regions

Hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) are transfusion transmissible infections (TTIs) agents that threaten the safety of the blood supply. Surveillance of the variance of those viruses is an important way to monitor their diversity and evolution to improve safety in blood transfusion. In this study, we characterized the specimens of blood donors from 13 blood centers located in 5 Chinese regions. Samples collected between 2014 and 2017 were screened with serological and molecular tests conducted on Abbott ARCHITECT and m2000 platforms. Sequencing was used to determine the classifications. The HBV immune escape mutations were also analyzed for assessing vaccine breakthrough risks and challenges for diagnostic tests. For HIV, 11 genotypes or recombinants were identified. The predominant genotype was C, which accounts for 42%. For HBV, the genotypes of B, C and D were identified, with B and C predominating. The major subgenotype was B2, comprising 84.1% of all infections. 79 out of 113 (69.9%) samples carried escape mutations in the "a" determinant region with 69 (87.3%) multiple mutants and 15 (19%) escape mutants which will affect HBsAg detection. For HCV, 7 genotypes or subtypes were identified. The major genotype was 1b (48%), followed by 6a (16.7%) and 2a & 3a (10%). This study provides the information of diversity of HBV, HCV and HIV strains circulating in blood centers from 5 regions in China. These data can also be scientific basis for development of detection assays that mitigate the impact of viral diversity on performance. ImportanceThe prevalence of TTIs in blood donations is important for evaluating blood safety and it can also reflect the burden of these disease among populations. Virus variance is threat to blood safety due to it may affect assays detection by nucleic acid, antigen and antibody-based methods in blood donors. HIV, HBV and HCV exhibit high degrees of genetic diversity, with different strains predominating in different geographic locations. The aim of this study is to assess the diversity of HBV, HCV and HIV among blood donors in China. In this study, 13 blood centers located in 5 Chinese regions were involved and the most informative phylogenetic regions of each virus had been sequenced. This will benefit for viral monitoring by subtype/genotype analyses to determine whether the distributions of variants are changing over time and geographically, and to speculate whether previously rare subtypes are becoming established in blood donors in China.

genetics↗

bioRxiv2019

Biased M1 positive allosteric modulators reveal novel role of phospholipase D in M1-dependent rodent cortical plasticity

Highly selective positive allosteric modulators (PAMs) of the M1 subtype of muscarinic acetylcholine receptor have emerged as an exciting new approach for the potential improvement of cognitive function in patients suffering from Alzheimers disease and schizophrenia. M1 PAM discovery programs have produced a structurally diverse range of M1 PAMs with distinct pharmacological properties, including different levels of agonist activity and differences in signal bias. This includes the recent discovery of novel biased M1 PAMs that can potentiate coupling of M1 to activation of phospholipase C but not phospholipase D (PLD). However, little is known about the role of PLD in M1 signaling in native systems and it is not clear whether biased M1 PAMs will display differences in modulating M1-mediated responses in native tissue. We now report a series of studies using novel PLD inhibitors and PLD knockout mice to show that PLD is necessary for the induction of M1-dependent long-term depression (LTD) in the prefrontal cortex (PFC). Importantly, biased M1 PAMs that do not couple to PLD not only fail to potentiate orthosteric agonist-induced LTD but also block M1-dependent LTD in the PFC. In contrast, biased and non-biased M1 PAMs act similarly in potentiating M1-dependent electrophysiological responses that are PLD-independent. These findings demonstrate that PLD plays a critical role in the ability of M1 PAMs to modulate certain CNS functions and that biased M1 PAMs function differently in brain regions implicated in cognition.\n\nSummaryWe demonstrate a novel role of phospholipase D in M1-dependent rodent cortical plasticity and M1 PAMs that do not couple to phospholipase D have functionally distinct effects on cortical plasticity than non-biased M1 PAMs.

neuroscience↗

bioRxiv2019

FAP overexpression induce Epithelial-Mesenchymal Transition (EMT) in oral squamous cell carcinoma by down-regulating DPP9 gene.

FAP acts as a tumor promoter via epithelial-mesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC). The present study was designed to investigate the interaction proteins with FAP and explore the precise mechanism of FAP promoting EMT in OSCC. IP-MS analysis confirmed that DPP9 was an interacting protein of FAP. DPP9 was down-regulated in OSCC tissue samples compared with MNT using immunohistochemistry and quantitative-PCR detection. Lower DPP9 was correlated with unfavorable overall survival of patients with OSCC. Repressing DPP9 accelerates the proliferation of OSCC cells in vitro and in vivo. Mechanistically, overexpression of FAP downregulate the expression of the DPP9 and the effect of FAP on OSCC proliferation, migration, invasion and EMT could be reversed by up-regulated DPP9. Our study suggests that FAP could induce EMT and promote carcinogenesis in oral squamous cell carcinoma by down-regulating DPP9 gene. That will hint different dimension on therapy for patients with OSCC.

molecular biology↗

bioRxiv2019

Recombinase system-dependent copackaging strategy for highly efficient neurocircuit tracing

Mapping the detailed cell-type-specific input networks and neuronal projectomes are essential to understand brain function in normal and pathological states. However, several properties of current tracing systems, including labeling sensitivity, trans-synaptic efficiencies, reproducibility among different individuals and different Cre-driver animals, still remained unsatisfactory. Here, we developed MAP-ENVIVIDERS, a recombinase system-dependent vector mixing-based strategy for highly efficient neurocircuit tracing. MAP-ENVIVIDERS enhanced tracing efficiency of input networks across the whole brain, with over 10-fold improvement in diverse previously poor-labeled input brain regions and particularly, up to 70-fold enhancement in brainstem compared with the current standard rabies-virus-mediated systems. MAP-ENVIVIDERS was over 10-fold more sensitive for cell-type-specific labeling than previous strategies, enabling us to capture individual cell-type-specific neurons with extremely complex axonal branches and presynaptic axonal boutons, both about one order of magnitude than previously reported and considered. MAP-ENVIVIDERS provides powerful tools for deconstructing novel input/output circuitry towards functional studies and disorders-related mechanisms.

neuroscience↗

bioRxiv2019

PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2

Drug resistance is a major obstacle for the success of conventional anticancer therapy, and the development of drug resistance is at least partly attributed to tumor propagating cells (TPCs). Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen. We found that the TPC proportion was remarkably increased in resistant germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL subtypes. Elevated SOX2 was the determinant for resistance development, and SOX2 was phosphorylated by activated PI3K/AKT1 signaling, thus preventing ubiquitin-mediated SOX2 degradation. Furthermore, multiple factors, including BCR, integrins, chemokines and FGFR1/2 signaling, regulated PI3K/AKT1 activation. CDK6 in the GCB subtype and FGFR1/2 in the ABC subtype were SOX2 targets in the PI3K/AKT1 pathway. Chemical inhibition of PI3K/AKT1 in both subtypes, CDK6 in the GCB subtype, and FGFR1/2 in the ABC subtype significantly enhanced the susceptibility of resistant cells to CHO treatment. More importantly, PI3K and FGFR1/2 inhibitors but not a CDK6 inhibitor effectively suppressed the tumor growth of R-CHO-resistant DLBCL cells, most likely by converting TPCs to chemo-sensitive differentiated cells. Therefore, this pro-differentiation therapy against TPCs warrants further study in clinical trials for the treatment of resistant DLBCL.

cancer biology↗

bioRxiv2019

Source-Sink Modifications Affect Leaf Senescence and Grain Mass in Wheat

A field experiment was performed in wheat to investigate the responses of flag leaf and grain to sink/source manipulations. The results showed that half-degraining delayed but defoliation (only flag leaf left) enhanced the leaf senescence. Sink/source manipulations influenced the content of reactive oxygen species of flag leaf and the content of phytohormones including cytokinins, indoleacetic 3-acid, gibberellin 3, salicylic acid and jasmonic acid in the defoliated flag leaf (DL) and grain (DG), half-degrained flag leaf (HL) and grain (HG). An iTRAQ based quantitative proteomic analysis indicated that at 16 days after manipulation a total of 97 and 59 differentially expressed proteins (DEPs) from various functional categories were observed in HL and DL groups, respectively, compared with control and 115 and 121 DEPs were observed in HG and DG groups, respectively. GO annotation terms of DEPs mainly included carbon fixation, hydrogen peroxide catabolic process, chloroplast and cytoplasm, oxidoreductase activity and glutamate synthase activity in flag leaf of manipulated plants; organonitrogen compound metabolic process, cytoplasm, vacuolar membrane, CoA carboxylase activity, starch synthase activity and nutrient reservoir activity in grain of manipulated plants. KEGG pathway enrichment analysis revealed that photosynthesis, carbon, nitrogen and pyruvate metabolisms and glycolysis/gluconeogenesis were the most remarkable processes for sink/source manipulations. Sink/source manipulations affected the activities of - and {beta}- amylases and proteinases. Ultimately, manipulations changed the mass per grain. In conclusion, manipulations to change the sink/source ratio affect the levels of hormones, activities of hydrolytic enzymes, metabolisms of carbon, nitrogen and other main compounds, stress resistance, the leaf senescence, and ultimately influence the grain mass.

physiology↗

bioRxiv2018

Narrowly confined and glomerulus-specific onset latencies of odor-evoked calcium transients in the periglomerular cells of the mouse main olfactory bulb

Odor information is transmitted from olfactory sensory neurons to principal neurons at the glomeruli of the olfactory bulb. The intraglomerular neuronal circuit also includes hundreds of GABAergic interneurons referred to as periglomerular (PG) cells. Stimulus selectivity is well correlated among PG cells that are associated with the same glomerulus, consistent with their highly homogeneous sensory inputs. However, much less is known about the temporal aspects of their activity, including the temporal coordination of their odor-evoked responses. As many PG cells within a glomerular module respond to the same stimulus, the extent to which their activity is temporally aligned will affect the temporal profile of their population inhibitory inputs. Using random-access high-speed two-photon microscopy, we recorded the odor-evoked calcium transients of mouse PG cells and compared the onset latency and rise time among neurons putatively associated with the same and different glomeruli. Whereas the overall onset latencies of odor-evoked transients were distributed across a ~150 ms time window, those from cells putatively associated with the same glomerulus were confined to a much narrower window of several tens of milliseconds. This result suggests that onset latency primarily depends on the associated glomerulus. We also observed glomerular specificity in the rise time. The glomerulus-specific temporal pattern of odor-evoked activity implies that the temporal patterns of inhibitory inputs are unique to individual glomerulus-odor pairs, which may contribute to efficient shaping of the temporal pattern of activity in the principal neurons.

neuroscience↗

bioRxiv2018

Widespread and polymorphous noncoding amino acid residues in human sperm proteome

Proteins are usually deciphered by translation of the coding genome; however, their amino acid residues are seldom determined directly across the proteome. Herein, we describe a systematic workflow for identifying all possible protein residues that differ from the coding genome, termed noncoded amino acids (ncAAs). By measuring the mass differences between the coding amino acids and the actual protein residues in human spermatozoa, over a million nonzero delta masses were detected, fallen into 424 high-quality Gaussian clusters and 571 high-confidence ncAAs spanning 29,053 protein sites. Most ncAAs are novel with unresolved side-chains and discriminative between healthy individuals and patients with oligoasthenospermia. For validation, 40 out of 98 ncAAs that matched with amino acid substitutions were confirmed by exon sequencing. This workflow revealed the widespread existence of previously unreported ncAAs in the sperm proteome, which represents a new dimension on the understanding of amino acid polymorphisms at the proteomic level.\n\nHighlightsO_LI571 ncAAs spanning 108,000 protein sites were identified in human sperm proteome.\nC_LIO_LIMost ncAAs are novel with unresolved sidechains and found at unreported protein sites.\nC_LIO_LIExon sequencing confirmed 40 of 98 ncAAs that matched with amino acid substitutions.\nC_LIO_LIMany ncAAs are linked with disease and have potential for diagnosis and targeting.\nC_LI\n\neTOC BlurbWe describe a systematic identification of all possible protein residues that were not encoded by their genomic sequences. A total of 571 high-confidence most novel noncoded amino acids were identified in human sperm proteome, corresponding to over 108,000 ncAA-containing protein sites. For validation, 40 out of 98 ncAAs that matched to amino acid substitutions were confirmed by exon sequencing. These ncAAs are discriminative between individuals and expand our understanding of amino acid polymorphisms in human proteomes and diseases.

molecular biology↗