Rodent pups exposed to hyperoxia develop lung changes similar to bronchopulmonary dysplasia (BPD) in extremely premature infants. Oxidative stress from hyperoxia can injure developing lungs through endoplasmic reticulum (ER) stress. Early caffeine treatment decreases the rate of BPD, but the mechanisms remain unclear. We hypothesized that caffeine attenuates hyperoxia-induced lung injury through its chemical chaperone property. Sprague-Dawley rat pups were raised either in 90 (hyperoxia) or 21% (normoxia) oxygen from (P1) to (P10) and then recovered in 21% oxygen until P21. Caffeine (20 mg/kg) or normal saline (control) was administered intraperitoneally daily starting from P2. Lungs were inflation-fixed for histology or snap-frozen for immunoblots. Blood caffeine levels were measured in treated pups at euthanasia and were found to be 18.4 ± 4.9 μg/ml. Hyperoxia impaired alveolar formation and increased ER stress markers and downstream effectors; caffeine treatment attenuated these changes at P10. Caffeine also attenuated the hyperoxia-induced activation of cyclooxygenase-2 and markers of apoptosis. In conclusion, hyperoxia-induced alveolar growth impairment is mediated, in part, by ER stress. Early caffeine treatment protects developing lungs from hyperoxia-induced injury by attenuating ER stress.
Background: Ventilation with higher PaCO2 goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO2 goal than in previous trials. Objective: To determine the clinical benefits and safety of higher PaCO2 goals for ventilated preterm infants. Study Design: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO2 target between 55 and 65 mm Hg (7.3– 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7– 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18–22 months corrected age. Results: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p < 0.05). Conclusion: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.
A pulsed laser activated cell sorter (PLACS) integrated with 3D sheathless inertial focusing sorts cells with high purity at high‐throughput using a single layer PDMS channel that can be easily fabricated at low cost. Sort purity of >90% is achieved at a throughput of 10 000 particles s−1 without severe dilution effects from high volume sheath flows.
Double-stranded probes are homogeneous biosensors for rapid detection of specific nucleotide sequences. These double-stranded probes have been applied in various molecular sensing applications, such as real-time polymerase chain reaction and detection of bacterial 16S rRNA. In this study, we present the design and optimization of double-stranded probes for single-cell gene expression analysis in living cells. With alternating DNA/LNA monomers for optimizing the stability and specificity, we show that the probe is stable in living cells for over 72 hours post-transfection and is capable of detecting changes in gene expression induced by external stimuli. The probes can be delivered to a large number of cells simultaneously by cationic liposomal transfection or to individual cells selectively by photothermal delivery. We also demonstrate that the probe quantifies intracellular mRNA in living cells through the use of an equilibrium analysis. With its effectiveness and performance, the double-stranded probe represents a broadly applicable approach for large-scale single-cell gene expression analysis toward numerous biomedical applications, such as systems biology, cancer, and drug screening.
PurposeThe purpose of this paper is to examine the relationship between sense of calling and work meaningfulness with job crafting as a mediator and spiritual leadership as a moderator.Design/methodology/approachAdopting a three-wave procedure, data were collected from 333 participants across industries from Guangdong province, China.FindingsResults indicate that job crafting partially mediates the relationship between employee sense of calling and work meaningfulness. Moreover, the positive relationship between job crafting and work meaningfulness is more significant when spiritual leadership is high than when it is low. Additionally, spiritual leadership moderates the indirect relationship of sense of calling and work meaningfulness through job crafting such that the indirect effect of sense of calling is stronger when spiritual leadership is high than when it is low.Originality/valueBased on self-determination theory, this study adds to current literatures examining the importance of sense of calling on a person's career and explores the boundary conditions, which bring desirable outcomes.
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