Biology subjects

Chi, Y.

Publications and source records attributed to Chi, Y..

47 records · Page 3Linked to original sources

bioRxiv2022

Antimicrobial Susceptibility Test by Surface-enhanced Raman Scattering of Bacterial Metabolites directly from Positive Blood Cultures

Effective management of sepsis requires timely administration of appropriate antibiotics; therefore, a reliable and rapid antimicrobial susceptibility test (AST) is crucial. To meet clinical needs, we developed a novel AST, referred to as SERS-AST, based on the surface-enhanced Raman Scattering (SERS) technology. In this study, we applied SERS-AST to eight most common pathogens causing bacteremia, including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, E. faecium, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii. Seven different antibiotics were tested, including oxacillin, levofloxacin, vancomycin, ampicillin, cefotaxime, ceftazidime, levofloxacin, and imipenem. SERS-AST determines antibiotic susceptibility of bacteria directly from positive blood cultures based on variations in bacterial SERS signals derived from secreted purines and their derivatives. The whole process could be completed within 4 hours, and the agreement rates between SERS-AST and VITEK 2 results were 96% for Gram-positive bacteria and 97% for Gram-negative bacteria.

microbiology↗

bioRxiv2021

Recut: a Concurrent Framework for Sparse Reconstruction of Neuronal Morphology

Advancement in modern neuroscience is bottlenecked by neural reconstruction, a process that extracts 3D neuron morphology (typically in tree structures) from image volumes at the scale of hundreds of GBs. We introduce Recut, an automated and accelerated neural reconstruction pipeline, which provides a unified, and domain specific sparse data representation with 79x reduction in the memory footprint. Recuts reconstruction can process 111 Kneurons/day or 79 TB/day on a 24-core workstation, placing the throughput bottleneck back on microscopic imaging time. Recut allows the full brain of a mouse to be processed in memory on a single server, at 89.5x higher throughput over existing I/O-bounded methods. Recut is also the first fully parallelized end-to-end automated reconstruction pipeline for light microscopy, yielding tree morphologies closer to ground truth than the state-of-the-art while removing involved manual steps and disk I/O overheads. We also optimized pipeline stages to linear algorithmic complexity for scalability in dense settings and allow the most timing-critical stages to optionally run on accelerated hardware.

neuroscience↗

bioRxiv2021

NAD metabolism modulates mitochondrial function and inflammation and prevents progression of diabetic kidney disease

Diabetes mellitus is the leading cause of cardiovascular and renal disease in the United States. In spite of the beneficial interventions available for patients with diabetes, there remains a need for additional therapeutic targets and therapies in diabetic kidney disease (DKD). Inflammation and oxidative stress are increasingly recognized as important causes of renal diseases. Inflammation is closely associated with mitochondrial damage. The molecular connection between inflammation and mitochondrial metabolism remains to be elucidated. Recently, nicotinamide adenine nucleotide (NAD+) metabolism has been found to regulate immune function and inflammation. In the present studies we tested the hypothesis that enhancing NAD metabolism could prevent inflammation in and progression of DKD. We found that treatment of db/db mice with type 2 diabetes with nicotinamide riboside (NR) prevented several manifestations of kidney dysfunction (i.e., albuminuria, increased urinary kidney injury marker-1 (KIM1) excretion and pathologic changes). These effects were associated with decreased inflammation, at least in part via inhibiting the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway. An antagonist of the serum stimulator of interferon genes (STING) and whole-body STING deletion in diabetic mice showed similar renoprotection. Further analysis found that NR increased SIRT3 activity and improved mitochondrial function, which led to decreased mitochondrial DNA damage, a trigger for mitochondrial DNA leakage which activates the cGAS-STING pathway. Overall, these data show that NR supplementation boosted NAD metabolism to augment mitochondrial function, reducing inflammation and thereby preventing progression of diabetic kidney disease.

pathology↗

bioRxiv2021

Isolation and in vitro culture of primary pia mater cells

The meninges remain an unexplored area of neurobiology. These structures play host to dozens of morbid pathologies. This protocol provides a reliable way to identify and isolate pial cells from mice using robust markers of pial identity in mouse and human tissues. We describe a protocol for the extraction of pia mater cells from mice and their culture as primary cells in vitro. Using an array of transcriptomic, histological, and flow cytometric analyses, we identified Icam1 and Slc38a2 as two novel pia mater markers in vitro and in vivo. Our results confirm the fibroblastoid nature of pial cells and their ability to form a sheet-like layer that covers the brain parenchyma. To our knowledge, this is the first published protocol for the isolation, tissue culture, and marker identification of pial cells from mice. These findings will enable researchers in CNS barriers to describe pial cell functions in both health and disease.

neuroscience↗

bioRxiv2020

The regulation of liver gene expression by carbohydrates is mouse strain specific

C57BL/6J and BALB/cJ mouse strains were analyzed by deep mRNA sequencing of the liver in the fasted state and following ingestion of standard laboratory mouse chow supplemented with plain drinking water or water containing 20% glucose, sucrose or fructose. Supplementation with these carbohydrates induced unique extents and temporal changes in gene expressions in a strain specific manner. Fructose and sucrose stimulated gene changes peaked at 3 h postprandial, whereas glucose effects peaked at 12 h postprandial in C57BL/6J mice and at 6 h postprandial in BABL/cJ mice. Network analyses revealed that fructose changed genes were primarily involved in lipid metabolism and were more complex in C57BL/6J than in BALB/cJ mice. These data demonstrate that there are qualitative and quantitative differences in the normal physiological responses of the liver between these two strains of mice and C57BL/6J is more sensitive to sugar intake than BALB/cJ.

genomics↗

bioRxiv2020

HTCC as a highly effective polymeric inhibitor of SARS-CoV-2 and MERS-CoV

The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the healthcare measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of previously developed by us HTCC compound (N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride), which may be used as potential inhibitor of currently circulating highly pathogenic coronaviruses - SARS-CoV-2 and MERS-CoV.

microbiology↗

bioRxiv2020

A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19.

systems biology↗

bioRxiv2019

Inhibiting the prostaglandin transporter PGT induces non-canonical thermogenesis at thermoneutrality

ABSTRACT / SUMMARYProstaglandins play fundamental roles in adipose tissue function. While prostaglandin F2 inhibits adipogenesis, prostaglandin E2 promotes adipose beiging. PGF2 and PGE2 are both inactivated through uptake by the plasma membrane transporter (PGT). We hypothesized that inhibiting PGT would increase PGF2 and PGE2 levels, thereby reducing white fat expansion and inducing beiging. Consistent with this hypothesis, inhibiting PGT in mice on high fat diet via genetic knockout or pharmacological blockade reduced body fat stores and induced thermogenesis at thermoneutrality. Inguinal white adipose tissue (iWAT) of these mice exhibited robust UCP1-independent thermogenesis characterized by mitochondrial expansion, coupling of O2 consumption to ATP synthesis, and induction of the creatine pathway. Enhanced coupled respiration persisted in PGT-KO iWAT adipocytes in a creatine shuttle-dependent manner. Thus, inhibiting PGT increases mitochondrial biogenesis and coupled respiration--each supported by the creatine pathway in a system lacking UCP1 expression--revealing PGT as a promising drug target against obesity.

physiology↗

bioRxiv2019

Effects of Shift-Work on the Carotid Artery and Cerebral Blood Flow of SHR Rats and WKY Rats

ObjectiveThe objective was to investigate the effects of shift-work (SW) on the carotid arteries.\n\nMethodsThis study used two inverted photoperiods (inverted light:dark [ILD]16:8 and ILD12:12) to create the SW model. We recorded the rhythm and performed serological tests, carotid ultrasound, magnetic resonance imaging, and carotid biopsy.\n\nResultsSW induced elevated blood pressure and increased angiotensin-II, apolipoprotein E, blood glucose, and triglycerides. SW increased the carotid intima-media thickness. SW led to the development of carotid arterial thrombosis, reduced cerebral blood flow, and increased the number of collagen fibers, expression of angiotensin receptor and low-density lipoprotein receptor in the carotid arteries. SW decreased 3-hydroxy-3-methylglutaryl-CoA reductase and nitric oxide. SW induced the atherosclerotic plaque in the aorta. Multiple results of SHR were worse than WKY rats.\n\nConclusionSW can induce metabolic disorders and elevated blood pressure. SW can cause intima-media thickening of the carotid artery and aorta atherosclerosis. SW may result in carotid arterial thrombosis and affect cerebral blood flow. Hypertension can aggravate the adverse effects of SW.

pathology↗

bioRxiv2019

Precise implantation of super-paramagnetic iron oxide (SPIO) nanoparticles in hippocampus with external rotating magnetic field (RMF) produces rapid antidepressent effects in mice

BackgroundTMS is an effective anti-depression method commonly used in clinical practice, but it also faces the problems of low spatial resolution, treatment parameters to be optimized and limitation in mechanism research.\n\nObjectiveTo develop a precise magnetic stimulation anti-depression method for the scientific research of magnetic stimulation, especially the mechanism research in animal experiments.\n\nMethodsThe cytotoxicity test was conducted in advance to ensure the security of intervention from SPIO nanoparticles and RMF. In animal experiments, 300nl SPIO solution was injected into the right hippocampus of the CUMS model mice, and then treated experimental group mice with rotating magnetic field for five days. The Sucrose Preference Test (SPT), the Forced Swim Test (FST) and BDNF expression levels were used to evaluate the antidepressant effect of this method.\n\nResultsNo significant decrease of cell viability was observed when the iron concentration is between 52.2{micro}g/ml and 208.8{micro}g/ml. And the application of RMF with a certain frequency was considered to be safe in the cytotoxicity test. When treated with SPIO+RMF, the sucrose preference of SPIO+RMF group mice increased markedly (n=9, p<0.01 vs. CUMS), the FST immobile time reduced (n=8, P<0.05 vs. CUMS) and the BDNF level in the hippocampus was significantly up-regulated (n=5, P<0.01 vs. CUMS). However, merely SPIO intervention failed to be effective.\n\nConclusionswhen intervened with external rotating magnetic field, the SPIO nanoparticles injected into the right hippocampus could produce rapid antidepressent effects in mice.

neuroscience↗

bioRxiv2018

The effect of heavy metal contamination on human and animal health in the vicinity of a zinc smelter

A diagnosis of heavy metal poisoning in sheep living on pasture in the vicinity of a zinc smelter was made based on laboratory tests and clinical signs in livestock in the Wumeng mountain area of China. Heavy metal contamination has generated serious harm to the health of local farmers after passing through the food chain. The levels of copper, zinc, cadmium, and lead in irrigation water, soil, forages, and animal tissues were measured in samples taken from within the vicinity of a zinc smelter and control samples. Heavy metal concentrations in foods (corn, rice, and wheat) and human tissues (blood and hair) from local farmers living in affected areas and controls were also determined. Hematological values were determined in human and animal samples. The copper, zinc, cadmium, and lead concentrations in irrigation water, soils, and forages were markedly higher than the levels in healthy pastures. Cadmium and lead concentrations were 177.82 and 16.61 times greater in forages than controls, respectively, and 68.71 and 15.66 times greater in soils than controls, respectively. Heavy metal concentrations in food (corn, rice, and wheat) in affected areas were markedly higher than in the control samples. Cadmium and lead concentrations in the tissues of affected sheep were markedly higher than in control animals (P< 0.01). Cadmium and lead concentrations in blood and hair samples from affected farmers were markedly higher than the control samples (P < 0.01). The occurrence of anemia in affected persons and animals followed a hypochromic and microcytic pattern. The intake of cadmium and lead was estimated according to herbage ingestion rates. It was found that the levels of cadmium and lead accumulated in sheep through the ingestion of vegetation growing in the sites closest to the zinc smelter were approximately 3.36 mg Cd/kg body wt./day and 38.47 mg Pb/kg body wt./day. This surpassed the fatal dosages for sheep of 1.13 mg Cd/kg body wt/day and 4.42 mg Pb/kg body wt./day. Serum total antioxidant capacity in affected humans and animals was significantly lower than in the controls (P < 0.01). The serum protein parameters in affected humans and animals were significantly reduced (P < 0.01). It was therefore concluded that heavy metal contamination has caused serious harm to sheep in this area. The heavy metal concentrations in food and grain also pose a significant risk to human health in the Chinese Wumeng mountain area.

ecology↗