Alzheimer's disease (AD) is a progressively debilitating neurodegenerative condition primarily affecting the elderly. Emerging research suggests that microRNAs (miRNAs) play a role in the development ...of AD. This study investigates the impact of miR‐107‐5p on neurological damage, oxidative stress, and immune responses in AD. We utilized APP/PS1 mice as AD mouse models and C57BL/6 J mice as controls. AD mice received treatment with agomir miR‐107‐5p (to overexpress miR‐107‐5p) or BAY11‐7082 (an NF‐κB pathway inhibitor). We evaluated learning and memory abilities through the Morris water maze test. Histopathological changes, hippocampal neuron distribution, and apoptosis were assessed using hematoxylin–eosin, Nissl, and TUNEL staining. Reactive oxygen species (ROS) levels, amyloid‐Aβ (Aβ1‐40/42) contents, and inflammatory factors (TNF‐α, IL‐6, IL‐1β) in hippocampal tissues were measured using ROS kits and enzyme‐linked immunosorbent assay (ELISA). Microglial activation in hippocampal tissues was observed under a fluorescence microscope. miR‐107‐5p's binding to TLR4 was predicted via the TargetScan database and confirmed through a dual‐luciferase assay. miR‐107‐5p expression, along with TLR4, APOE, and TREM2 in hippocampal tissue homogenate, and NF‐κB p65 protein expression in the nucleus and cytoplasm were assessed via RT‐qPCR and Western blot. Overexpression of miR‐107‐5p ameliorated hippocampal neurological damage, oxidative stress, and immune responses. This was evidenced by improved enhanced learning/memory abilities, reduced Aβ1‐40 and Aβ1‐42 levels, diminished neuronal injuries, decreased ROS and TNF‐α, IL‐6, and IL‐1β levels, increased APOE and TREM2 levels, and suppressed microglial activation. miR‐107‐5p directly targeted and inhibited TLR4 expression, leading to reduced nuclear translocation of NF‐κB p65 in the NF‐κB pathway. Inhibition of the NF‐κB pathway similarly improved neurological damage, oxidative stress, and immune response in AD mice. miR‐107‐5p exerts its beneficial effects by suppressing the TLR4/NF‐κB pathway, ultimately ameliorating neurological damage, oxidative stress, and immune responses in AD mice.
An asymmetric Friedel–Crafts alkylation reaction of 2-furfuryl ketones with β-trifluoromethyl enones has been developed via formal trienamine catalysis of a bifunctional primary amine-thiourea ...substance derived from L-tert-leucine, delivering the furan derivatives incorporating a stereogenic trifluoromethyl (CF3) group in good to high yields with excellent enantioselectivity.
Background Very preterm infants often require mechanical ventilation. However, objective criteria to predict the outcomes of extubation in very premature neonates remain lacking. The aim of this ...study was to investigate the accuracy of the spontaneous breathing trial (SBT) using a combined model of continuous positive airway pressure (CPAP) and low-level pressure support ventilation (PSV) to predict the extubation outcomes of preterm infants with gestational age < 32 weeks. Methods Preterm infants with gestational age < 32 weeks, birth weight < 1500 g and requiring mechanical ventilation were selected for the study. All infants underwent a 10-minute SBT using CPAP combined with low-level PSV prior to the planned extubation. Then, the infants were extubated within 1 h after SBT. The outcomes of extubation were considered successful if the neonates did not require reintubation 72 h after extubation. Results A total of 119 eligible preterm infants were enrolled in the study, with a median gestational age of 28.9 (27.1-30.3) weeks and a median birth weight of 1100 (900-1350) g. In total, 101 of all infants had successful extubation, 18 of whom failed and eventually had to be reintubated. Of the 102 infants who achieved SBT, 99 were successfully extubated, and 15 of the 17 infants who did not pass SBT had failed extubation. Finally, the diagnostic value for SBT could be assessed with a sensitivity of 98%, a specificity of 83.3%, a positive predictive value of 97.1% and a negative predictive value of 88.2%. Conclusion SBT using a combined CPAP + low-level PSV model can predict the outcomes of extubation in very preterm infants with high sensitivity and specificity.
Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the ...physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.
Abstract A nanocarrier, namely, hydroxylethyl-chitosan nanoparticles was developed in this research for delivering antioxidants with 6-hydroxy-2, 5, 7, 8-tetra-methylchromane-2-carboxylic acid ...(trolox) as a model antioxidant. The trolox-encapsulated chitosan nanoparticles (trolox-CS NPs) were prepared by modifying chitosan with epoxyethane, which self-assembled into NPs and entrapped trolox, and then characterized by their size, size distribution, morphology and in vitro trolox release profile. Intracellular trafficking of CS NPs was observed. The anti-oxidant effect and potential mechanism of trolox-CS NPs were subsequently investigated in RAW264.7 cells. The effects of trolox-CS NPs on RAW264.7 cells damaged by tert-butylhydroperoxide (t-BHP) were determined by MTT assay for cell viability, MDA assay for membrane lipid peroxidation, JC-1 probe and Annexin V-FITC/PI double staining for mitochondria membrane potential (MMP) and RAW264.7 apoptosis, respectively. The trolox-CS NPs significantly improved cell viability and reduced MDA content compared with those of cells treated with free trolox. The trolox-CS NPs treatment inhibited MMP collapse and RAW264.7 apoptosis more obviously than free trolox. Molecular basis of apoptosis studied by western blotting revealed that trolox-CS NPs may block mitochondria-mediated apoptosis pathway through up-regulation of Bcl-2 and down-regulation of Bax and inhibiting the activation of pro-caspase 3, PARP and Bid.
Hydrogen production from vegetable oil via a chemical looping process with hematite oxygen carriers has been carried out in a fixed-bed reactor at 1023.15–1173.15 K. The lattice oxygen release ...process and crystalline transformation for the oxygen carrier in the reaction process are investigated. Results indicate that the maximum H2 composition achieved in the chemical looping hydrogen stage is over 91.72% when hematite oxygen carriers consisting of Fe2O3, Al2O3 and SiO2 are used. The active component Fe2O3 in oxygen carriers represents three reduced peaks corresponding to the crystalline form transition from Fe2O3 to Fe3O4. Up to 96.13% of the lattice oxygen in Fe2O3 can be consumed in the reduction process. The deep reduction of FeO to Fe represents a lower reaction rate with the exhaustion of the lattice. The maximum carbon conversion efficiency of vegetable oil of 79.10% when the ratio of water to oil is 1.2 and hydrogen-rich gas with a highest concentration of 91.72% are achieved in the chemical looping reforming stage and H2 production stage, respectively. The impurities in the gas are ascribed to the carbon deposition and steam reaction in the chemical looping process. The micrographs of fresh and used oxygen carriers present irregular and blocky structures, sintering is not observed after the multi-cycle reaction process. The crystalline form and reaction activity remain stable after 20-cycle experiments, suggesting that the hematite oxygen carrier is a promising candidate for hydrogen generation from vegetable oil via the chemical looping process.
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•CLR of vegetable oil with hematite oxygen carrier was used to generate H2 production.•96.13% active lattice oxygen in Fe2O3 was consumed with the maximum reaction rate 0.0142%/s.•The maximum H2 concentration generated in CLH stage is over 91.72%.•H2O helps to C conversion in CLR of vegetable oil, but is harmful to H2 production in subsequent CLH stage.•20-cycle experiments confirm the stability of hematite oxygen carrier in CLR- CLH process.
There is compelling evidence that postural instability occurs at very early clinical stages of Parkinson's disease (PD), making it tempting to speculate that changes in postural sway may even occur ...at a prodromal phase. Studies estimate that approximately half of patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) will eventually develop PD, so RBD may be an indicator of prodromal PD. This study was undertaken to investigate postural sway and its relation to stereopsis function in patients with RBD. We examined 24 patients with polysomnography-confirmed RBD and 23 healthy, sex-and age-matched control subjects. Postural sway was measured with an accelerometer at the center of mass at the lower spine. Subjects were asked to stand quietly for 30s under two usual conditions (eyes open and eyes closed) and three challenging conditions (eyes open with dual task, eyes closed with dual task, and tandem standing). Stereopsis was assessed using the Titmus fly test. RBD patients showed an increased variability of trunk acceleration and a decrease of smoothness of sway, compared to control subjects. These differences reached significance in the challenging conditions. RBD patients demonstrated significant impairment in stereopsis. There were statistically significant correlations between log seconds of arc of the Titmus test and some sway parameters within the RBD group. RBD patients with abnormal stereopsis showed a significant increase of JERK values compared to patients with normal stereopsis in the challenging conditions. Our results indicate that idiopathic RBD patients, especially with abnormal stereopsis, have subtle signs of postural instability under challenging conditions. Postural sway performance may serve as a biological marker for prodromal PD.
Telmisartan, an angiotensin II type 1–receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive ...impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced Aβ42, APP, BACE1, RAGE, and NF-κB p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain.
MicroRNAs （miRNAs） are -21 nucleotide （nt）, endogenous RNAs that regulate gene expression in plants. Increasing evidence suggests that miRNAs play an important role in species-specific development in ...plants. However, the detailed miRNA profile divergence has not been performed among tomato species. In this study, the small RNA （sRNA） profiles of Solanum lycopersicum cultivar 9706 and Solanum habrochaites species PI 134417 were obtained by deep sequencing. Sixty-three known miRNA families were identified from these two species, of which 39 were common. Further miRNA profile comparison showed that 24 known non-conserved miRNA families were species-specific between these two tomato species. In addition, six conserved miRNA families displayed an apparent divergent expression pattern between the two tomato species. Our results suggested that species-specific, non-conserved miRNAs and divergent expression of conserved miRNAs might contribute to developmental changes and phenotypic variation between the two tomato species. Twenty new miRNAs were also identified in S. lycopersicum. This research significantly increases the number of known miRNA families in tomato and provides the first set of small RNAs in S. habrochaites. It also suggests that miRNAs have an important role in species-specific plant developmental regulation.
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