Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

Designing and Implementing an Advanced Big Data Governance Platform

Contemporary mainstream big data governance platforms are built atop the big data ecosystem components,offering a one-stop development and analysis governance platform for the collection,transmission,storage,cleansing,transformation,querying and analysis,data development,publishing,and subscription,sharing and exchange,management,and services of massive data.These platforms serve various role members who have internal and external data needs.However,in the era of big data,the rapid update and iteration of big data technologies,the diversification of data businesses,and the exponential growth of data present more challenges and uncertainties to the construction of big data governance platforms.This paper discusses how to effectively build a data governance platform under the big data system from the perspectives of functional architecture,logical architecture,data architecture,and functional design.

A comprehensive diagnostic system of ultra-thin liquid sheet targets

To meet the demands of laser-ion acceleration at a high repetition rate,we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets(LSTs).The spatially resolved rapid characterizations of an LST’s thickness,flatness,tilt angle and position are fulfilled by different subsystems with high accuracy.With the help of the diagnostic system,we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets.Control methods for the flatness and tilt angle of LSTs have also been provided,which are essential for applications of laser-driven ion acceleration and others.

Synchronous post-acceleration of laser-driven protons in helical coil targets by controlling the current dispersion

Post-acceleration of protons in helical coil targets driven by intense,ultrashort laser pulses can enhance ion energy by utilizing the transient current from the targets’self-discharge.The acceleration length of protons can exceed a few millimeters,and the acceleration gradient is of the order of GeV/m.How to ensure the synchronization between the accelerating electric field and the protons is a crucial problem for efficient post-acceleration.In this paper,we study how the electric field mismatch induced by current dispersion affects the synchronous acceleration of protons.We propose a scheme using a two-stage helical coil to control the current dispersion.With optimized parameters,the energy gain of protons is increased by four times.Proton energy is expected to reach 45 MeV using a hundreds-of-terawatts laser,or more than 100 MeV using a petawatt laser,by controlling the current dispersion.

A Dietary Source of High Level of Fluoroquinolone Tolerance in mcr-Carrying Gram-Negative Bacteria

The emergence of antibiotic tolerance,characterized by the prolonged survival of bacteria following antibiotic exposure,in natural bacterial populations,especially in pathogens carrying antibiotic resistance genes,has been an increasing threat to public health.However,the major causes contributing to the formation of antibiotic tolerance and underlying molecular mechanisms are yet poorly understood.Herein,we show that potassium sorbate(PS),a widely used food additive,triggers a high level of fluoroquinolone tolerance in bacteria carrying mobile colistin resistance gene mcr.Mechanistic studies demonstrate that PS treatment results in the accumulation of intracellular fumarate,which activates bacterial two-component system and decreases the expression level of outer membrane protein OmpF,thereby reducing the uptake of ciprofloxacin.In addition,the supplementation of PS inhibits aerobic respiration,reduces reactive oxygen species production and alleviates DNA damage caused by bactericidal antibiotics.Furthermore,we demonstrate that succinate,an intermediate product of the tricarboxylic acid cycle,overcomes PS-mediated ciprofloxacin tolerance.In multiple animal models,ciprofloxacin treatment displays failure outcomes in PS preadministrated animals,including comparable survival and bacterial loads with the vehicle group.Taken together,our works offer novel mechanistic insights into the development of antibiotic tolerance and uncover potential risks associated with PS use.