Protective effect of grifolin against brain injury in an acute cerebral ischemia rat model

Purpose: To evaluate the protective effects of grifolin against brain injury in an acute cerebral ischemia rat model.Methods: Rats were assigned to five groups: control, negative control, and grifolin (50, 100, and 200 mg/kg, p.o.) treated groups, which received the drug for 2 weeks. All the animals were sacrificed at the end of the protocol, and tissue homogenates were prepared from isolated brain tissue. Glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO), as oxidative stress indicators, were determined for the tissue homogenates of the ischemic rats. Inflammatory mediators (cytokines and nuclear factor kappa B p65, NF κB), DNA damage, and ATP and caspase 3 levels in the tissue homogenates were also assessed.Results: Treatment with grifolin increased SOD and GPX significantly and decreased MDA and NO levels in tissue homogenates of the cerebral ischemic rats compared with those in the negative control group (p < 0.05). Treatment with grifolin also attenuated the altered levels of inflammatory mediators (cytokines and NF-κB), caspase 3, and ATP levels in the tissue homogenate of cerebral ischemic rats (p < 0.05). The results of comet assay on the tissue homogenate suggest that treatment with grifolin reduced or prevented damage.Conclusions: The results show that treatment with grifolin protects against neuronal damage in acute cerebral ischemic rats via its anti-inflammatory and anti-oxidant properties.Keywords: Neuroprotection, Cerebral ischemia, Brain injury, DNA, Grifolin, Anti oxidan

Nucleic Acid and Nanomaterial Synergistic Amplification Enables Dual Targets of Ultrasensitive Fluorescence Quantification to Improve the Efficacy of Clinical Tuberculosis Diagnosis

Interferon-γ (IFN-γ) release assays (IGRAs) are constrained by the limited diagnostic performance of a single indicator and the excessive Mycobacterium tuberculosis (Mtb) antigen stimulation time. This study presents a simultaneous, homogeneous, rapid, and ultrasensitive fluorescence quantification strategy for IFN-γ and IFN-γ-induced protein 10 (IP-10). This method relies on the high-affinity binding of aptamers to IFN-γ and IP-10, the enzyme-free catalytic hairpin assembly reaction, and the heightened sensitivity of CdTe quantum dots to Ag+ and hairpin structure C-Ag+-C and carbon dots to Hg2+ and hairpin structure T-Hg2+-T. Under optimized conditions, the selectivity of IFN-γ and IP-10 was excellent, with a linear range spanning from 1 to 100 ag/mL and low limits of detection of 0.3 and 0.5 ag/mL, respectively. Clinical practicality was confirmed through testing of 57 clinical samples. The dual-indicator combination detection showed 92.8% specificity and 93.1% sensitivity, with an area under the curve of 0.899, representing an improvement over the single-indicator approach. The Mtb antigen stimulation time was reduced to 8 h for 6/7 clinical samples. These findings underscore the potential of our approach to enhance the efficiency and performance of a tuberculosis (TB) clinical diagnosis

Coexistence of blaKPC-2 and blaNDM-1 in one IncHI5 plasmid confers transferable carbapenem resistance from a clinical isolate of Klebsiella michiganensis in China

ABSTRACT: Objectives: This study firstly identified an IncHI5 plasmid pK254-KPC_NDM co-carrying two different class carbapenemase genes blaKPC-2 and blaNDM-1 in Klebsiella michiganensis K254. Methods: The strain K254 was sequenced by high-throughput genome sequencing. A detailed genomic and phenotypic characterization of pK254-KPC_NDM was performed. Results: pK254-KPC_NDM displayed the conserve IncHI5 backbone and carried a resistant accessory region: Tn1696-related transposon Tn7414 containing blaKPC-2 and blaNDM-1. A sequence comparison was applied to a collection of four Tn1696-related transposons (Tn7414–Tn7417) harbouring carbapenemase genes. For all these four transposons, the blaNDM-1 was carried by Tn125 derivatives within three different mobile genetic elements. Tn7414 further acquired another carbapenemase gene, blaKPC-2, because of the integration of the local blaKPC-2 genetic environment from Tn6296, resulting in the high-level carbapenem resistance of K. michiganensis K254. The conjugal transfer and plasmid stability experiments confirmed that pK254-KPC_NDM could be transferred intercellularly and keep the stable vertical inheritance in different bacteria, which would contribute to the further dissemination of multiple carbapenemase genes and enhance the adaption and survival of K. michiganensis under complex and diverse antimicrobial selection pressures. Conclusion: This study was the first to report the K. michiganensis isolate coharbouring blaKPC-2 and blaNDM-1 in the Tn1696-related transposon in IncHI5 plasmid. The emergence of novel transposons simultaneously carrying multiple carbapenemase genes might contribute to the further dissemination of high-level carbapenem resistance in the isolates of the hospital settings and pose new challenges for the treatment of nosocomial infection

Geographic Variation in Mortality of Acute Myocardial Infarction and Association With Health Care Accessibility in Beijing, 2007 to 2018

Background Little is known about geographic variation in acute myocardial infarction (AMI) mortality within fast‐developing megacities and whether changes in health care accessibility correspond to changes in AMI mortality at the small‐area level. Methods and Results We included data of 94 106 AMI deaths during 2007 to 2018 from the Beijing Cardiovascular Disease Surveillance System in this ecological study. We estimated AMI mortality for 307 townships during consecutive 3‐year periods with a Bayesian spatial model. Township‐level health care accessibility was measured using an enhanced 2‐step floating catchment area method. Linear regression models were used to examine the association between health care accessibility and AMI mortality. During 2007 to 2018, median AMI mortality in townships declined from 86.3 (95% CI, 34.2–173.8) to 49.4 (95% CI, 30.5–73.7) per 100 000 population. The decrease in AMI mortality was larger in townships where health care accessibility increased more rapidly. Geographic inequality, defined as the ratio of the 90th to 10th percentile of mortality in townships, increased from 3.4 to 3.8. In total, 86.3% (265/307) of townships had an increase in health care accessibility. Each 10% increase in health care accessibility was associated with a −0.71% (95% CI, −1.08% to −0.33%) change in AMI mortality. Conclusions Geographic disparities in AMI mortality among Beijing townships are large and increasing. A relative increase in township‐level health care accessibility is associated with a relative decrease in AMI mortality. Targeted improvement of health care accessibility in areas with high AMI mortality may help reduce AMI burden and improve its geographic inequality in megacities

Driving Time to the Nearest Percutaneous Coronary Intervention-Capable Hospital and the Risk of Case Fatality in Patients with Acute Myocardial Infarction in Beijing

Timely arrival at a hospital capable of percutaneous coronary intervention (PCI) is critical in treating acute myocardial infarction (AMI). We examined the association between driving time to the nearest PCI-capable hospital and case fatality among AMI patients. A total of 142,474 AMI events during 2013–2019 from the Beijing Cardiovascular Disease Surveillance System were included in this cross-sectional study. The driving time from the residential address to the nearest PCI-capable hospital was calculated. Logistic regression was used to estimate the risk of AMI death associated with driving time. In 2019, 54.5% of patients lived within a 15-min drive to a PCI-capable hospital, with a higher proportion in urban than peri-urban areas (71.2% vs. 31.8%, p p value) for AMI fatality risk associated with driving times 16–30, 31–45, and >45 min were 1.068 (95% CI 1.033–1.104, p p p < 0.001), respectively. Despite the high accessibility to PCI-capable hospitals for AMI patients in Beijing, inequality between urban and peri-urban areas exists. A longer driving time is associated with an elevated AMI fatality risk. These findings may help guide the allocation of health resources

Trends and Inequalities in the Incidence of Acute Myocardial Infarction among Beijing Townships, 2007&ndash;2018

Acute myocardial infarction (AMI) poses a serious disease burden in China, but studies on small-area characteristics of AMI incidence are lacking. We therefore examined temporal trends and geographic variations in AMI incidence at the township level in Beijing. In this cross-sectional analysis, 259,830 AMI events during 2007&ndash;2018 from the Beijing Cardiovascular Disease Surveillance System were included. We estimated AMI incidence for 307 consistent townships during consecutive 3-year periods with a Bayesian spatial model. From 2007 to 2018, the median AMI incidence in townships increased from 216.3 to 231.6 per 100,000, with a greater relative increase in young and middle-aged males (35&ndash;49 years: 54.2%; 50&ndash;64 years: 33.2%). The most pronounced increases in the relative inequalities was observed among young residents (2.1 to 2.8 for males and 2.8 to 3.4 for females). Townships with high rates and larger relative increases were primarily located in Beijing&rsquo;s northeastern and southwestern peri-urban areas. However, large increases among young and middle-aged males were observed throughout peri-urban areas. AMI incidence and their changes over time varied substantially at the township level in Beijing, especially among young adults. Targeted mitigation strategies are required for high-risk populations and areas to reduce health disparities across Beijing

Active DNA unwinding and transport by a membrane-adapted helicase nanopore.

Nanoscale transport through nanopores and live-cell membranes plays a vital role in both key biological processes as well as biosensing and DNA sequencing. Active translocation of DNA through these nanopores usually needs enzyme assistance. Here we present a nanopore derived from truncated helicase E1 of bovine papillomavirus (BPV) with a lumen diameter of c.a. 1.3 nm. Cryogenic&nbsp;electron microscopy (cryo-EM) imaging and single channel recording confirm its insertion into planar lipid bilayer (BLM). The helicase nanopore in BLM allows the passive single-stranded DNA (ssDNA) transport and retains the helicase activity in vitro. Furthermore, we incorporate this helicase nanopore into the live cell membrane of HEK293T cells, and monitor the ssDNA delivery into the cell real-time at single molecule level. This type of nanopore is expected to provide an interesting tool to study the biophysics of biomotors in vitro, with potential applications in biosensing, drug delivery and real-time single cell analysis