Stroke is the leading cause of disabilities and cognitive deficits, accounting for 5.2% of all mortalities worldwide. Transient or permanent occlusion of cerebral vessels leads to ischemic strokes, ...which constitutes the majority of strokes. Ischemic strokes induce brain infarcts, along with cerebral tissue death and focal neuronal damage. The infarct size and neurological severity after ischemic stroke episodes depends on the time period since occurrence, the severity of ischemia, systemic blood pressure, vein systems and location of infarcts, amongst others. Ischemic stroke is a complex disease, and neuronal injuries after ischemic strokes have been the focus of current studies. The present review will provide a basic pathological background of ischemic stroke and cerebral infarcts. Moreover, the major mechanisms underlying ischemic stroke and neuronal injuries are summarized. This review will also briefly summarize some representative clinical trials and up-to-date treatments that have been applied to stroke and brain infarcts.
A copper-catalyzed system has been introduced for the enantioselective defluoroalkylation of linear 1-(trifluoromethyl)alkenes through C–F activation to synthesize various gem-difluoroalkenes as ...carbonyl mimics. For the first time, arylboronate-activated alkyl Grignard reagents were uncovered in this cross-coupling reaction. Mechanistic studies confirmed that the tetraorganoborate complexes generated in situ were the key reactive species for this transformation.
•Photocrosslinkable biomimetic chitosan derivative PCCs-GMA was synthesized.•Biomimetic PCCs-GMA hydrogels showed tunable mechanical and swelling properties.•PCCs-GMA hydrogels showed better blood ...compatibility than Cs-GMA hydrogels.•PCCs-GMA hydrogels showed low protein adsorption comparable with PEG-DA hydrogels.
Photocrosslinkable biomimetic chitosan derivative, glycidyl methacrylate-phosphorylcholine-chitosan (PCCs-GMA) was synthesized through the combination of Atherton-Todd reaction for coupling phosphorylcholine and ring opening reaction of epoxides for attaching GMA, and confirmed by 1H and 31P NMR and Fourier transform infrared (FTIR) spectroscopy. The photo-crosslinking reaction of PCCs-GMA with different degree of substitution (DS) of GMA allowed the formation of biomimetic hydrogels with tunable mechanical and swelling properties. Cold crystallization behaviors ascribed to their restrained freezing bound water were investigated using differential scanning calorimetry (DSC). The rheological and swelling behaviors, hemolysis as well as protein sorption of PCCs-GMA hydrogels were investigated in terms of the DS of GMA, using fibrinogen, bovine serum albumin and lysozyme as model proteins. Low irreversible protein sorption and non hemolytic results indicated that photo-crosslinked PCCs-GMA hydrogels may offer a promising candidate material with resistance to protein fouling in biomedical applications.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) play a critical role in most translational and clinical applications. Although glucose starvation (GS) has been evaluated during ...cellular purification, there has been no comprehensive evaluation of the transcriptional heterogeneity of these cells. Here, we applied GS for 3 days starting at day 10 of differentiation, and then, harvested hiPSC-CMs at day 20 for single-cell RNA sequencing (scRNA-seq). We found that GS dramatically reduced the proportion of non-cardiomyocytes cells and increased the number of late-stage cardiomyocytes. We also recorded an increase in the expression of MYH6, MYH7, ACTN2, TNNT2, and several other genes associated with the structural and functional maturation of cardiomyocytes. Further analysis indicated that these changes were focused on the signaling pathways involved in the regulation of the actin cytoskeleton, cardiac muscle development, and cardiac muscle contraction. Finally, pseudotime analysis revealed that GS hiPSC-CMs developed in a more mature direction. Together, these results suggest that GS treatment improves the purity and maturation of hiPSC-CMs, which should increase the feasibility of hiPSC-CMs applications.
Display omitted
•ScRNA-Seq analysis was performed for hiPSC-CMs subjected to glucose starvation.•Glucose starvation increases the subpopulation of cardiomyocytes in the late stage.•Glucose starvation improves the feasibility of hiPSC-CMs application.
The highly efficient direct catalytic reductive amination of ketones with diphenylmethanamine catalyzed by iridium–phosphoramidite complexes is described. As an effective coupling partner, ...diphenylmethanamine is suitable for a wide range of ketones to provide chiral amines in high yields and enantioselectivity. The chiral monodentate phosphoramidite ligands are tunable and competent to accommodate substrates with different structures.
Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic ...lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD.
In practical electric vehicle applications, the noise of original discharging/charging voltage (DCV) signals are inevitable, which comes from electromagnetic interference and the measurement noise of ...the sensors. To solve such problems, the Discrete Wavelet Transform (DWT) based state of charge (SOC) estimation method is proposed in this paper. Through a multi-resolution analysis, the original DCV signals with noise are decomposed into different frequency sub-bands. The desired de-noised DCV signals are then reconstructed by utilizing the inverse discrete wavelet transform, based on the sure rule. With the de-noised DCV signal, the SOC and the parameters are obtained using the adaptive extended Kalman Filter algorithm, and the adaptive forgetting factor recursive least square method. Simulation and experimental results show that the SOC estimation error is less than 1%, which indicates an effective improvement in SOC estimation accuracy.
Acidified CO2 fracturing is a viable method for increasing production in deep, tight sandstone reservoirs. However, the potential mechanism of changes in pore structure and mechanical properties of ...sandstone under acidified CO2 supercritical composite is not clear. Understanding this mechanism is important for the study of crack initiation and extension in tight sandstone reservoirs. This study utilizes sandstone samples from the Xujiahe Formation reservoir in Rongchang District as experimental specimens. The primary focus is to analyze the changes in pore structure and mechanical properties of these samples after acidification–supercritical CO2 composite action. Nuclear magnetic resonance (NMR) and uniaxial compression tests are employed as the main investigative techniques. The results show that there was a physicochemical synergy between the acidification–supercritical CO2 composite effect; the crack initial stress, damage stress, and peak stress of the sandstone after 16 MPa supercritical CO2 acidification treatment were reduced by 20%, 49.5%, and 49.8%, respectively; the crack volumetric strain accelerated and the sandstone evolved from brittle to ductile damage; and the larger pore space and microcracks of the sandstone increased significantly after the treatment, which can be attributed to the gradual dissolution of intergranular cement leading to the formation of new pores connected to the existing pore network. The change mechanism of sandstone after acidification–supercritical CO2 compound treatment is also proposed.
A presynaptic protein closely related to Parkinson's disease (PD), α-synuclein (α-Syn), has been studied extensively regarding its pathogenic mechanisms. As a physiological protein in presynapses, ...however, α-Syn's physiological function remains unclear. Its location in nerve terminals and effects on membrane fusion also imply its functional role in synaptic transmission, including its possible interaction with high-curvature membranes
its N-terminus and amorphous C-terminus. PD-related mutants that disrupt the membrane interaction (e.g., A30P and G51D) additionally suggest a relationship between α-Syn's pathogenic mechanisms and physiological roles through the membrane binding. Here, we summarize recent research on how α-Syn and its variants interact with membranes and influence synaptic transmission. We list several membrane-related connections between the protein's physiological function and the pathological mechanisms that stand to expand current understandings of α-Syn.
Various methods for human reliability analysis have been developed, but a rigorous approach to quantitatively comparing these methods is still lacking. This research proposed a Bayesian approach with ...an attempt to address this problem. The Bayesian approach is based on ensemble modeling, which outputs the weighted average of the human error probability predictions by the human reliability analysis methods to be compared. Before incorporating any human performance data, the weights in the ensemble model represent the prior probabilities of or one’s prior beliefs in the human reliability analysis methods. Using human performance data, the weights can be updated based on Bayes’ rule to reflect one’s updated beliefs in the human reliability analysis methods. The ensemble model with updated weights itself can be further used as a posterior predictive model for human reliability. The proposed approach is demonstrated using the human performance data collected from the international human reliability analysis empirical study. The results show that the posterior beliefs vary with the data set used in the analysis. Future research using a larger human performance data set is expected to reach more conclusive comparisons.
•Bayesian approach to quantitative HRA method comparison.•Ensemble modeling for HEP prediction.•Uncertainty in HEP predicted by an HRA method.•Analyst-to-analyst variability in HEP estimates.•Demonstration with human performance data from international HRA study.
PDF
